Association of Pharmacological Treatments with Long-Term Pain Control in Patients with Knee Osteoarthritis: a Systematic Review and Meta-Analysis

Supplementary Online Content

Gregori D, Giacovelli G, Minto C, et al. Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis. JAMA. doi:10.1001/jama.2018.19319

eTable 1A. Final search strategy for PubMed eTable 1B. Final search strategy for Scopus eTable 1C. Final search strategy for Embase eTable 1D. Final search strategy for Web of Science eTable 1E. Final search strategy for Cochrane Central Register of Controlled Trials eTable 2. Hierarchy of tools for patient-reported outcomes assessment eTable 3. Pain (primary outcome): league table – when trials at high risk of bias were excluded eTable 4. Pain (primary outcome): league table – All trials eTable 5. Physical function (secondary outcome): league table eTable 6. Physical function (secondary outcome): summary table of results when trials at high risk of bias were excluded eTable 7. Joint space narrowing (secondary outcome): summary table of results reported as Mean Difference (in mm) and as Standardized Mean Difference eTable 8. Joint space narrowing (secondary outcome): league table eTable 9. Joint space narrowing (secondary outcome): summary table of results when trials at high risk of bias were excluded eTable 10A. Summary of results for the sensitivity analyses, including clinical and statistical sensitivities eTable 10B1. Post-hoc sensitivity analysis using a Fixed effect model instead of the Random effect model used as main analysis eTable 10B2. Post-hoc sensitivity analysis using an empirical informative prior instead of the uninformative prior used as main analysis eFigure 1A. Pain (primary outcome): Network plot - All trials eFigure 1B. Pain (primary outcome): Network plot when trials at high risk of bias were excluded eFigure 2. Pain (primary outcome): Forest plot (estimates as Standardized Mean Difference) - All trials eFigure 3. Pain (primary outcome): Forest plot (estimates as Standardized Mean Difference) when trials at high risk of bias were excluded eFigure 4A. Pain (primary outcome): SUCRA plots when trials at high risk of bias were excluded eFigure 4B. Pain (primary outcome): rankogram plots when trials at high risk of bias were excluded

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 eFigure 4C. Pain (primary outcome): ranking forest plot when trials at high risk of bias were excluded eFigure 5. Pain (primary outcome): SUCRA forest plot – All trials eFigure 5A. Pain (primary outcome): SUCRA plots – All trials eFigure 5B. Pain (primary outcome): rankogram plots – All trials eFigure 5C. Pain (primary outcome): ranking forest plot – All trials eFigure 6. Network plot for comparisons on the secondary outcome physical function eFigure 7. Physical Function (secondary outcome): Forest plot eFigure 8. Physical function (secondary outcome): SUCRA forest plot eFigure 8A. Physical function (secondary outcome): SUCRA plots eFigure 8B. Physical function (secondary outcome): rankogram plots eFigure 8C. Physical function (secondary outcome): ranking forest plot eFigure 9. Network plot for comparisons on the secondary outcome joint space narrowing eFigure 10. Joint space narrowing (secondary outcome): Forest plot eFigure 11. Joint space narrowing (secondary outcome): SUCRA forest plot eFigure 11A. Joint space narrowing (secondary outcome): SUCRA plots eFigure 11B. Joint space narrowing (secondary outcome): rankogram plots

eFigure 11C. Joint space narrowing (secondary outcome): ranking forest plot

This supplementary material has been provided by the authors to give readers additional information about their work.

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 485 Search strategy: eTables 1 486 eTable 1A - Final search strategy for PubMed #ID Topic or intervention Query Records #1 Disease ("Osteoarthritis, Knee"[Mesh]) OR ("Osteoarthritis"[Mesh] AND "Knee 38927 Joint"[Mesh]) OR ("Osteoarthritis"[Mesh] AND (Knee[Title/Abstract] OR Knees[Title/Abstract])) OR ((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract]) AND "Knee Joint"[Mesh]) OR ("Knee Osteoarthritis"[Title/Abstract] OR "Knee Osteoarthritides"[Title/Abstract] OR "Osteoarthritis of Knee"[Title/Abstract] OR "Osteoarthritis of Knees"[Title/Abstract] OR "Knee OA"[Title/Abstract] OR "Knees OA"[Title/Abstract]) OR ((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract]) AND (Knee[Title/Abstract] OR Knees[Title/Abstract])) #2 Study design "Randomized Controlled Trial" [Publication Type] OR 735467 Randomized[Title/Abstract] OR Randomised[Title/Abstract] OR Randomization[Title/Abstract] OR Randomisation[Title/Abstract] #3 Aceclofenac "aceclofenac" [Supplementary Concept] OR Aceclofenac[Title/Abstract] 15 OR Falcol[Title/Abstract] OR "Clanza CR"[Title/Abstract] OR Preservex[Title/Abstract] OR Biofenac[Title/Abstract] OR Sanein[Title/Abstract] OR Beofenac[Title/Abstract] OR Aital[Title/Abstract] OR Airtal[Title/Abstract] OR Bristaflam[Title/Abstract] OR Gerbin[Title/Abstract] #4 Acetaminophen "Acetaminophen"[Mesh] OR Acetaminophen[Title/Abstract] OR 178 Hydroxyacetanilide[Title/Abstract] OR APAP[Title/Abstract] OR Acetamidophenol[Title/Abstract] OR Paracetamol[Title/Abstract] OR Acephen[Title/Abstract] OR Acetaco[Title/Abstract] OR Tylenol[Title/Abstract] OR "Anacin-3"[Title/Abstract] OR "Anacin 3"[Title/Abstract] OR Anacin3[Title/Abstract] OR Datril[Title/Abstract] OR Panadol[Title/Abstract] OR Acamol[Title/Abstract] OR Algotropyl[Title/Abstract] #5 Androstenedione "Androstenedione"[Mesh] OR Androstenedione[Title/Abstract] OR 0 Androstene[Title/Abstract] #6 ASA "Aspirin"[Mesh] OR Aspirin[Title/Abstract] OR "Acetylsalicylic Acid"[Title/Abstract] OR Acylpyrin[Title/Abstract] OR 31 Aloxiprimum[Title/Abstract] OR Colfarit[Title/Abstract] OR Dispril[Title/Abstract] OR Easprin[Title/Abstract] OR Ecotrin[Title/Abstract] OR Endosprin[Title/Abstract] OR Magnecyl[Title/Abstract] OR Micristin[Title/Abstract] OR Polopirin[Title/Abstract] OR Polopiryna[Title/Abstract] OR Solprin[Title/Abstract] OR Solupsan[Title/Abstract] OR Zorprin[Title/Abstract] OR Acetysal[Title/Abstract] #7 Benoxaprofen "benoxaprofen" [Supplementary Concept] OR 2 Benoxaprofen[Title/Abstract] OR Oraflex[Title/Abstract] #8 Betamethasone "Betamethasone"[Mesh] OR Betamethasone[Title/Abstract] OR 15 Flubenisolone[Title/Abstract] OR Betadexamethasone[Title/Abstract] OR 15 Celestona[Title/Abstract] OR Cellestoderm[Title/Abstract] OR Celeston[Title/Abstract] OR Celestone[Title/Abstract] #9 Calcitonin "Calcitonin"[Mesh] OR Calcitonin[Title/Abstract] OR Calcitrin[Title/Abstract] OR Thyrocalcitonin[Title/Abstract] OR "Ciba 11 47175-BA"[Title/Abstract] OR "Ciba 47175 BA"[Title/Abstract] OR "Ciba 47175BA"[Title/Abstract] #10 Capsaicin "Capsaicin"[Mesh] OR Capsaicin[Title/Abstract] OR Capsaicine[Title/Abstract] OR Axsain[Title/Abstract] OR 9 Zacin[Title/Abstract] OR Capsidol[Title/Abstract] OR Zostrix[Title/Abstract] OR Capzasin[Title/Abstract] OR Gelcen[Title/Abstract] OR Katrum[Title/Abstract] OR "Capsicum

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records Farmaya"[Title/Abstract] OR Capsin[Title/Abstract] #11 Celecoxib "Celecoxib"[Mesh] OR Celecoxib[Title/Abstract] OR 120 Celebrex[Title/Abstract] #12 Chondroitin "Chondroitin Sulfates"[Mesh] OR "Chondroitin Sulfate"[Title/Abstract] 124 OR Chondroitin[Title/Abstract] OR Chonsurid[Title/Abstract] OR Translagen[Title/Abstract] OR Blutal[Title/Abstract] #13 Cindunistat "cindunistat"[Supplementary Concept] OR Cindunistat[Title/Abstract] 1 #14 Cortivazol "cortivazol"[Supplementary Concept] OR Cortivazol[Title/Abstract] 1 #15 Dexamethasone "Dexamethasone"[Mesh] OR Dexamethasone[Title/Abstract] OR 12 Methylfluorprednisolone[Title/Abstract] OR Hexadecadrol[Title/Abstract] OR Decameth[Title/Abstract] OR Decaspray[Title/Abstract] OR Dexasone[Title/Abstract] OR Dexpak[Title/Abstract] OR Maxidex[Title/Abstract] OR Millicorten[Title/Abstract] OR Oradexon[Title/Abstract] OR Decaject[Title/Abstract] OR Hexadrol[Title/Abstract] #16 Diacerein "diacetylrhein" [Supplementary Concept] OR Diacerein[Title/Abstract] 29 OR Diacerhein[Title/Abstract] OR Diacetylrhein[Title/Abstract] OR "Diacetyl-rhein"[Title/Abstract] OR Zondar[Title/Abstract] #17 Diclofenac "Diclofenac"[Mesh] OR Diclofenac[Title/Abstract] OR 211 Diclophenac[Title/Abstract] OR Dicrofenac[Title/Abstract] OR Dichlofenal[Title/Abstract] OR "Diclonate P"[Title/Abstract] OR Feloran[Title/Abstract] OR Voltarol[Title/Abstract] OR Novapirina[Title/Abstract] OR Orthofen[Title/Abstract] OR Ortofen[Title/Abstract] OR Orthophen[Title/Abstract] OR Voltaren[Title/Abstract] #18 Diflunisal "Diflunisal"[Mesh] OR Diflunisal[Title/Abstract] OR 7 Dolobid[Title/Abstract] OR Dolocid[Title/Abstract] OR Dolobis[Title/Abstract] OR NuDifunisal[Title/Abstract] OR NovoDiflunisal[Title/Abstract] OR ApoDiflunisal[Title/Abstract] #19 Doxycycline "Doxycycline"[Mesh] OR Doxycycline[Title/Abstract] OR "Alpha-6- 17 Deoxyoxytetracycline"[Title/Abstract] OR "Alpha 6 Deoxyoxytetracycline"[Title/Abstract] OR Oracea[Title/Abstract] OR Periostat[Title/Abstract] OR "Vibra-Tabs"[Title/Abstract] OR "Vibra Tabs"[Title/Abstract] OR VibraTabs[Title/Abstract] OR Vibramycin[Title/Abstract] OR Vibravenos[Title/Abstract] OR Atridox[Title/Abstract] OR Doryx[Title/Abstract] OR Hydramycin[Title/Abstract] #20 Duloxetine "Duloxetine Hydrochloride"[Mesh] OR Duloxetine[Title/Abstract] OR 18 Propanamide[Title/Abstract] OR Cymbalta[Title/Abstract] #21 Eltenac "eltenac" [Supplementary Concept] OR Eltenac[Title/Abstract] OR 2 Telzenac[Title/Abstract] #22 Etodolac "Etodolac"[Mesh] OR Etodolac[Title/Abstract] OR "Etodolic 22 Acid"[Title/Abstract] OR Ultradol[Title/Abstract] OR Lodine[Title/Abstract] OR Ramodar[Title/Abstract] #23 Etoricoxib "etoricoxib" [Supplementary Concept] OR Etoricoxib[Title/Abstract] OR 24 Arcoxia[Title/Abstract] #24 Fentanyl "Fentanyl"[Mesh] OR Fentanyl[Title/Abstract] OR 13 Phentanyl[Title/Abstract] OR Fentanest[Title/Abstract] OR Sublimaze[Title/Abstract] OR Duragesic[Title/Abstract] OR Durogesic[Title/Abstract] OR Fentora[Title/Abstract] #25 Flurbiprofen "Flurbiprofen"[Mesh] OR Flurbiprofen[Title/Abstract] OR 15 Flubiprofen[Title/Abstract] OR Fluriproben[Title/Abstract] OR Cebutid[Title/Abstract] OR Dobrofen[Title/Abstract] OR Flugalin[Title/Abstract] OR Froben[Title/Abstract] OR "Neo Artrol"[Title/Abstract] OR Ocufen[Title/Abstract] OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records Ocuflur[Title/Abstract] OR Strefen[Title/Abstract] OR Ansaid[Title/Abstract] #26 Corticosteroids "Adrenal Cortex Hormones"[Mesh] OR "Adrenal Cortex 153 Hormones"[Title/Abstract] OR Corticosteroid[Title/Abstract] OR Corticosteroids[Title/Abstract] OR Corticoid[Title/Abstract] OR Corticoids[Title/Abstract] #27 Glucosamine "Glucosamine"[Mesh] OR Glucosamine[Title/Abstract] OR 165 Hespercorbin[Title/Abstract] OR Dona[Title/Abstract] OR Xicil[Title/Abstract] #28 Hyaluronic acid "Hyaluronic Acid"[Mesh] OR "Hyaluronic Acid" [Title/Abstract] OR "Amo 367 Vitrax"[Title/Abstract] OR Biolon[Title/Abstract] OR Etamucine[Title/Abstract] OR Hyaluronan[Title/Abstract] OR Hyvisc[Title/Abstract] OR Luronit[Title/Abstract] OR Hyaluronate[Title/Abstract] OR Amvisc[Title/Abstract] OR Healon[Title/Abstract] OR Synvisc[Title/Abstract] OR Orthovisc[Title/Abstract] OR Hyalectin[Title/Abstract] OR Hyalgan[Title/Abstract] OR Vitrax[Title/Abstract] OR Ostenil[Title/Abstract] OR Hylan[Title/Abstract] OR Suplasyn[Title/Abstract] OR Arthrum[Title/Abstract] OR "Go- on"[Title/Abstract] OR Hyalart[Title/Abstract] OR Nuflexxa[Title/Abstract] OR Replasyn[Title/Abstract] OR Durolane[Title/Abstract] OR Supartz[Title/Abstract] #29 Hydrocortisone "Hydrocortisone"[Mesh] OR Hydrocortisone[Title/Abstract] OR 8 Cortisol[Title/Abstract] OR Epicortisol[Title/Abstract] OR Cortifair[Title/Abstract] OR Cortril[Title/Abstract] #30 Ibuprofen "Ibuprofen"[Mesh] OR Ibuprofen[Title/Abstract] OR 91 Ibumetin[Title/Abstract] OR "IP-82"[Title/Abstract] OR "IP 82"[Title/Abstract] OR IP82[Title/Abstract] OR Motrin[Title/Abstract] OR Nuprin[Title/Abstract] OR Rufen[Title/Abstract] OR Salprofen[Title/Abstract] OR "Trauma-Dolgit Gel"[Title/Abstract] OR "Trauma Dolgit Gel"[Title/Abstract] OR "TraumaDolgit Gel"[Title/Abstract] OR Brufen[Title/Abstract] #31 Indomethacin "Indomethacin"[Mesh] OR Indomethacin[Title/Abstract] OR 41 Indometacin[Title/Abstract] OR Amuno[Title/Abstract] OR Indocid[Title/Abstract] OR Metindol[Title/Abstract] OR "Indomet 140"[Title/Abstract] OR Osmosin[Title/Abstract] OR Indocin[Title/Abstract] #32 Ketoprofen "Ketoprofen"[Mesh] OR Ketoprofen[Title/Abstract] OR 22 "Benzoylhydratropic Acid"[Title/Abstract] OR Profenid[Title/Abstract] OR Alrheumum[Title/Abstract] OR Orudis[Title/Abstract] OR Alrheumat[Title/Abstract] #33 Ketorolac "Ketorolac"[Mesh] OR Ketorolac[Title/Abstract] OR Acular[Title/Abstract] 9 OR Toradol[Title/Abstract] #34 Licofelone "licofelone"[Supplementary Concept] OR Licofelone[Title/Abstract] 4 #35 Lornoxicam "lornoxicam"[Supplementary Concept] OR Lornoxicam[Title/Abstract] 6 OR Chlortenoxicam[Title/Abstract] OR Xefocam[Title/Abstract] #36 Lumiracoxib "lumiracoxib"[Supplementary Concept] OR Lumiracoxib[Title/Abstract] 9 OR Prexige[Title/Abstract] #37 MMP Inhibitors "Matrix Metalloproteinase Inhibitors"[Mesh] OR "Matrix 6 Metalloproteinase Inhibitors"[Title/Abstract] OR "Matrix Metalloproteinase Inhibitor"[Title/Abstract] OR "MMP Inhibitors"[Title/Abstract] OR "MMP Inhibitor"[Title/Abstract] OR "Stromelysin Inhibitors"[Title/Abstract] OR "Stromelysin Inhibitor"[Title/Abstract] OR "Gelatinase Inhibitors"[Title/Abstract] OR "Gelatinase Inhibitor"[Title/Abstract] OR "Collagenase Inhibitors"[Title/Abstract] OR "Collagenase Inhibitor"[Title/Abstract]

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #38 Meloxicam "meloxicam"[Supplementary Concept] OR Meloxicam[Title/Abstract] OR 21 Reumoxicam[Title/Abstract] OR Miloxicam[Title/Abstract] OR Movalis[Title/Abstract] OR Uticox[Title/Abstract] OR Mobic[Title/Abstract] OR Mobicox[Title/Abstract] OR Mobec[Title/Abstract] OR Masflex[Title/Abstract] OR Movicox[Title/Abstract] OR Parocin[Title/Abstract] #39 Metamizole "Dipyrone"[Mesh] OR Metamizole[Title/Abstract] OR 0 Dipyrone[Title/Abstract] OR "Noramidopyrine Methanesulfonate Sodium"[Title/Abstract] OR Metamizol[Title/Abstract] OR Methamizole[Title/Abstract] OR Dipyronium[Title/Abstract] OR Methampyrone[Title/Abstract] OR Novaminsulfone[Title/Abstract] OR Sulpyrin[Title/Abstract] OR Sulpyrine[Title/Abstract] OR Optalgin[Title/Abstract] OR Novalgin[Title/Abstract] OR Analgin[Title/Abstract] OR Narone[Title/Abstract] OR Biopyrin[Title/Abstract] OR "Noramidopyrine Methanesulfonate"[Title/Abstract] OR Normelubrine[Title/Abstract] OR Novalgetol[Title/Abstract] OR Pyralgin[Title/Abstract] OR Algopyrin[Title/Abstract] #40 Methylprednisolone "Methylprednisolone"[Mesh] OR Methylprednisolone[Title/Abstract] OR 42 Metipred[Title/Abstract] OR Urbason[Title/Abstract] OR Medrol[Title/Abstract] OR UrbasonSoluble[Title/Abstract] OR SoluMedrol[Title/Abstract] OR "A-MethaPred"[Title/Abstract] #41 Methylsulfonylmethane "dimethyl sulfone"[Supplementary Concept] OR "Dimethyl 16 Sulfone"[Title/Abstract] OR "Methyl Sulfonmethane"[Title/Abstract] OR Methylsulfonylmethane[Title/Abstract] OR "Methyl Sulfone"[Title/Abstract] #42 Nabumetone "nabumetone"[Supplementary Concept] OR Nabumetone[Title/Abstract] 25 OR Nabumeton[Title/Abstract] OR Arthraxan[Title/Abstract] OR Listran[Title/Abstract] OR Relafen[Title/Abstract] OR Relif[Title/Abstract] OR Relifex[Title/Abstract] OR Mebutan[Title/Abstract] OR Nabucox[Title/Abstract] #43 Naproxcinod "naproxen-n-butyl nitrate"[Supplementary Concept] OR 9 Naproxcinod[Title/Abstract] OR "NO-naproxen"[Title/Abstract] OR "Nitric Oxide Naproxen"[Title/Abstract] OR NicOx[Title/Abstract] #44 Naproxen "Naproxen"[Mesh] OR Naproxen[Title/Abstract] OR 108 Methoxypropiocin[Title/Abstract] OR MNPA[Title/Abstract] OR Anaprox[Title/Abstract] OR Naprosin[Title/Abstract] OR Naprosyn[Title/Abstract] OR Proxen[Title/Abstract] OR Synflex[Title/Abstract] OR Aleve[Title/Abstract] #45 Nimesulide "nimesulide"[Supplementary Concept] OR Nimesulide[Title/Abstract] OR 18 Aulin[Title/Abstract] OR Eskaflam[Title/Abstract] OR lizepat[Title/Abstract] OR Mesulid[Title/Abstract] OR Nexen[Title/Abstract] OR Nimesil[Title/Abstract] OR Redaflam[Title/Abstract] OR Antifloxil[Title/Abstract] OR Guaxan[Title/Abstract] #46 Opioids "Analgesics, Opioid"[Mesh] OR "Opioid Analgesics"[Title/Abstract] OR 114 "Opioid Analgesic"[Title/Abstract] OR Opioids[Title/Abstract] OR Opioid[Title/Abstract] #47 Oxaprozin Search (((((((("Osteoarthritis, Knee"[Mesh]) OR (("Osteoarthritis"[Mesh] 6 AND "Knee Joint"[Mesh]))) OR (("Osteoarthritis"[Mesh]) AND (Knee[Title/Abstract] OR Knees[Title/Abstract]))) OR (((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract])) AND "Knee Joint"[Mesh])) OR (("Knee Osteoarthritis"[Title/Abstract] OR "Knee Osteoarthritides"[Title/Abstract] OR "Osteoarthritis of Knee"[Title/Abstract] OR "Osteoarthritis of Knees"[Title/Abstract] OR "Knee OA"[Title/Abstract] OR "Knees OA"[Title/Abstract]))) OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records (((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract])) AND (Knee[Title/Abstract] OR Knees[Title/Abstract])))) AND ("oxaprozin"[Supplementary Concept] OR Oxaprozin[Title/Abstract] OR Danoprox[Title/Abstract] OR Dayrun[Title/Abstract] OR Daypro[Title/Abstract] #48 Parecoxib "parecoxib"[Supplementary Concept] OR Parecoxib[Title/Abstract] OR 1 Dynastat[Title/Abstract] #49 Pennsaid Pennsaid[Title/Abstract] AND (Randomized Controlled Trial[ptyp] OR 4 (Randomized[Title/Abstract] OR Randomised[Title/Abstract] OR Randomization[Title/Abstract] OR Randomisation[Title/Abstract]))) #50 Piroxicam "Piroxicam"[Mesh] OR Piroxicam[Title/Abstract] OR 58 Feldene[Title/Abstract] #51 Prednisolone "Prednisolone"[Mesh] OR Prednisolone[Title/Abstract] OR 35 Predate[Title/Abstract] OR Predonine[Title/Abstract] OR "Di-Adreson- F"[Title/Abstract] OR "DiAdreson F"[Title/Abstract] OR DiAdresonF[Title/Abstract] #52 Risedronate "Risedronate Sodium"[Mesh] OR Risedronate[Title/Abstract] OR 11 "Risedronic Acid"[Title/Abstract] OR Actonel[Title/Abstract] OR Atelvia[Title/Abstract] #53 Rofecoxib "rofecoxib"[Supplementary Concept] OR Rofecoxib[Title/Abstract] OR 38 Vioxx[Title/Abstract] #54 SAME "S-Adenosylmethionine"[Mesh] OR "S- 391 Adenosylmethionine"[Title/Abstract] OR SAME[Title/Abstract] OR "SAM- e"[Title/Abstract] OR AdoMet[Title/Abstract] OR "S-Adenosyl-L- Methionine"[Title/Abstract] OR "S Adenosyl L Methionine"[Title/Abstract] OR Ademetionine[Title/Abstract] OR "S Amet"[Title/Abstract] OR Samyr[Title/Abstract] OR Gumbaral[Title/Abstract] #55 Sprifermin "fibroblast growth factor 18"[Supplementary Concept] OR "Fibroblast 4 Growth Factor 18"[Title/Abstract] OR Sprifermin[Title/Abstract] #56 Steroids "Steroids"[Mesh] OR Steroid[Title/Abstract] OR Steroids[Title/Abstract] 174 #57 Strontium ranelate "strontium ranelate"[Supplementary Concept] OR "Strontium 12 Ranelate"[Title/Abstract] OR Protelos[Title/Abstract] #58 Sulindac "Sulindac"[Mesh] OR Sulindac[Title/Abstract] OR "Apo- 5 Sulin"[Title/Abstract] OR "Apo Sulin"[Title/Abstract] OR Arthrobid[Title/Abstract] OR Clinoril[Title/Abstract] OR Arthrocine[Title/Abstract] OR Klinoril[Title/Abstract] OR Sulindal[Title/Abstract] OR Chibret[Title/Abstract] OR Kenalin[Title/Abstract] OR "Novo-Sundac"[Title/Abstract] OR "Novo Sundac"[Title/Abstract] OR Aclin[Title/Abstract] OR Copal[Title/Abstract] #59 Tenidap "tenidap"[Supplementary Concept] OR Tenidap[Title/Abstract] 3 #60 Tenoxicam "tenoxicam"[Supplementary Concept] OR Tenoxicam[Title/Abstract] OR 12 Reutenox[Title/Abstract] OR Artriunic[Title/Abstract] OR Mobiflex[Title/Abstract] OR Tilcotil[Title/Abstract] #61 Tiaprofenic acid "tiaprofenic acid"[Supplementary Concept] OR "Tiaprofenic 9 Acid"[Title/Abstract] OR Flanid[Title/Abstract] OR "Nu- Tiaprofenic"[Title/Abstract] OR "PMS-Tiaprofenic"[Title/Abstract] OR Surgam[Title/Abstract] OR "Apo-Tiaprofenic"[Title/Abstract] OR "Novo- Tiaprofenic"[Title/Abstract] #62 Tolmetin-Na "Tolmetin"[Mesh] OR Tolmetin[Title/Abstract] OR Tolectin[Title/Abstract] 5 #63 Tramadol "Tramadol"[Mesh] OR Tramadol[Title/Abstract] OR 38 Tramundin[Title/Abstract] OR Biodalgic[Title/Abstract] OR Jutadol[Title/Abstract] OR Nobligan[Title/Abstract] OR Prontofort[Title/Abstract] OR Zytram[Title/Abstract] OR Takadol[Title/Abstract] OR Theradol[Title/Abstract] OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records Tiral[Title/Abstract] OR Topalgic[Title/Abstract] OR Tradol[Title/Abstract] OR TradolPuren[Title/Abstract] OR Tradonal[Title/Abstract] OR Tralgiol[Title/Abstract] OR Trama[Title/Abstract] OR TramaDorsch[Title/Abstract] OR Biokanol[Title/Abstract] OR Tramabeta[Title/Abstract] OR Tramadin[Title/Abstract] OR Tramadolratiopharm[Title/Abstract] OR Tramadoc[Title/Abstract] OR "Ranitidin 1A Pharma"[Title/Abstract] OR Trasedal[Title/Abstract] OR Ultram[Title/Abstract] OR "Xymel 50"[Title/Abstract] OR Zamudol[Title/Abstract] OR Zydol[Title/Abstract] OR TramadolDolgit[Title/Abstract] OR TramadolHameln[Title/Abstract] OR Tramadolor[Title/Abstract] OR Tramadura[Title/Abstract] OR Tramagetic[Title/Abstract] OR Tramagit[Title/Abstract] OR Tramake[Title/Abstract] OR Tramal[Title/Abstract] OR Tramex[Title/Abstract] OR Adolonta[Title/Abstract] OR Contramal[Title/Abstract] OR Amadol[Title/Abstract] #64 Triamcinolone "Triamcinolone"[Mesh] OR Triamcinolone[Title/Abstract] OR 67 Volon[Title/Abstract] OR Aristocort[Title/Abstract] #65 Trolamine salicylate "trolamine salicylate"[Supplementary Concept] OR "Trolamine 1 Salicylate" [Title/Abstract] OR "Triethanolamine Salicylate" [Title/Abstract] OR Myoflex[Title/Abstract] #66 Valdecoxib Search (((((((("Osteoarthritis, Knee"[Mesh]) OR (("Osteoarthritis"[Mesh] 5 AND "Knee Joint"[Mesh]))) OR (("Osteoarthritis"[Mesh]) AND (Knee[Title/Abstract] OR Knees[Title/Abstract]))) OR (((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract])) AND "Knee Joint"[Mesh])) OR (("Knee Osteoarthritis"[Title/Abstract] OR "Knee Osteoarthritides"[Title/Abstract] OR "Osteoarthritis of Knee"[Title/Abstract] OR "Osteoarthritis of Knees"[Title/Abstract] OR "Knee OA"[Title/Abstract] OR "Knees OA"[Title/Abstract]))) OR (((Osteoarthritis[Title/Abstract] OR Osteoarthritides[Title/Abstract] OR Arthritis[Title/Abstract] OR Arthritides[Title/Abstract])) AND (Knee[Title/Abstract] OR Knees[Title/Abstract])))) AND ("valdecoxib"[Supplementary Concept] OR Valdecoxib[Title/Abstract] OR Bextra[Title/Abstract] #67 Vitamin D "Vitamin D"[Mesh] OR "Vitamin D"[Title/Abstract] 32 #68 Vitamin E "Vitamin E"[Mesh] OR "Vitamin E"[Title/Abstract] 11 #69 Zoledronic acid "zoledronic acid"[Supplementary Concept] OR "Zoledronic 6 Acid"[Title/Abstract] OR Zoledronate[Title/Abstract] OR Zometa[Title/Abstract] #70 Final query #1 AND #2 AND (#3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 1834 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69) 487

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 488 eTable 1B - Final search strategy for Scopus #ID Topic or intervention Query Records #1 Disease (TITLE-ABS-KEY("knee osteoarthritis") OR TITLE-ABS-KEY("knee 57821 osteoarthritides") OR TITLE-ABS-KEY("osteoarthritis of knee") OR TITLE-ABS-KEY("osteoarthritis of knees") OR TITLE-ABS-KEY("knee OA")) OR ((TITLE-ABS-KEY("osteoarthritis") OR TITLE-ABS- KEY("osteoarthritides") OR TITLE-ABS-KEY("arthritis") OR TITLE- ABS-KEY("arthritides")) AND (TITLE-ABS-KEY("knee") OR TITLE- ABS-KEY("knees"))) #2 Study design (TITLE-ABS-KEY("Randomized") OR TITLE-ABS- 997847 KEY("Randomised") OR TITLE-ABS-KEY("Randomization") OR TITLE-ABS-KEY("Randomisation")) #3 Aceclofenac (TITLE-ABS-KEY("aceclofenac") OR TITLE-ABS-KEY("Falcol") OR 25 TITLE-ABS-KEY("Clanza CR") OR TITLE-ABS-KEY("Preservex") OR TITLE-ABS-KEY("Biofenac") OR TITLE-ABS-KEY("Sanein") OR TITLE-ABS-KEY("Beofenac") OR TITLE-ABS-KEY("Aital") OR TITLE- ABS-KEY("Airtal") OR TITLE-ABS-KEY("Bristaflam") OR TITLE-ABS- KEY("Gerbin")) #4 Acetaminophen (TITLE-ABS-KEY("Acetaminophen") OR TITLE-ABS- 633 KEY("Hydroxyacetanilide") OR TITLE-ABS-KEY("APAP") OR TITLE- ABS-KEY("Acetamidophenol") OR TITLE-ABS-KEY("Paracetamol") OR TITLE-ABS-KEY("Acephen") OR TITLE-ABS-KEY("Acetaco") OR TITLE-ABS-KEY("Tylenol") OR TITLE-ABS-KEY("Anacin-3") OR TITLE-ABS-KEY("Anacin 3") OR TITLE-ABS-KEY("Anacin3") OR TITLE-ABS-KEY("Datril") OR TITLE-ABS-KEY("Panadol") OR TITLE-ABS-KEY("Acamol") OR TITLE-ABS-KEY("Algotropyl")) #5 Androstenedione (TITLE-ABS-KEY("Androstenedione") OR TITLE-ABS- 1 KEY("Androstene")) #6 ASA (TITLE-ABS-KEY("Aspirin") OR TITLE-ABS-KEY("Acetylsalicylic 138 Acid") OR TITLE-ABS-KEY("Acylpyrin") OR TITLE-ABS- KEY("Aloxiprimum") OR TITLE-ABS-KEY("Colfarit") OR TITLE-ABS- KEY("Dispril") OR TITLE-ABS-KEY("Easprin") OR TITLE-ABS- KEY("Ecotrin") OR TITLE-ABS-KEY("Endosprin") OR TITLE-ABS- KEY("Magnecyl") OR TITLE-ABS-KEY("Micristin") OR TITLE-ABS- KEY("Polopirin") OR TITLE-ABS-KEY("Polopiryna") OR TITLE-ABS- KEY("Solprin") OR TITLE-ABS-KEY("Solupsan") OR TITLE-ABS- KEY("Zorprin") OR TITLE-ABS-KEY("Acetysal")) #7 Benoxaprofen (TITLE-ABS-KEY("Benoxaprofen") OR TITLE-ABS-KEY("Oraflex")) 2 #8 Betamethasone (TITLE-ABS-KEY("Betamethasone") OR TITLE-ABS- 37 KEY("Flubenisolone") OR TITLE-ABS-KEY("Betadexamethasone") OR TITLE-ABS-KEY("Celestona") OR TITLE-ABS- KEY("Cellestoderm") OR TITLE-ABS-KEY("Celeston") OR TITLE- ABS-KEY("Celestone")) #9 Calcitonin (TITLE-ABS-KEY("Calcitonin") OR TITLE-ABS-KEY("Calcitrin") OR 26 TITLE-ABS-KEY("Thyrocalcitonin") OR TITLE-ABS-KEY("Ciba 47175-BA") OR TITLE-ABS-KEY("Ciba 47175 BA") OR TITLE-ABS- KEY("Ciba 47175BA")) #10 Capsaicin (TITLE-ABS-KEY("Capsaicin") OR TITLE-ABS-KEY("Capsaicine") 62 OR TITLE-ABS-KEY("Axsain") OR TITLE-ABS-KEY("Zacin") OR TITLE-ABS-KEY("Capsidol") OR TITLE-ABS-KEY("Zostrix") OR TITLE-ABS-KEY("Capzasin") OR TITLE-ABS-KEY("Gelcen") OR TITLE-ABS-KEY("Katrum") OR TITLE-ABS-KEY("Capsicum Farmaya") OR TITLE-ABS-KEY("Capsin")) #11 Celecoxib (TITLE-ABS-KEY("Celecoxib") OR TITLE-ABS-KEY("Celebrex")) 269 #12 Chondroitin (TITLE-ABS-KEY("Chondroitin Sulfate") OR TITLE-ABS- 281 KEY("Chondroitin") OR TITLE-ABS-KEY("Chonsurid") OR TITLE- ABS-KEY("Translagen") OR TITLE-ABS-KEY("Blutal"))

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #13 Cindunistat (TITLE-ABS-KEY("Cindunistat")) 2 #14 Cortivazol (TITLE-ABS-KEY("Cortivazol")) 8 #15 Dexamethasone (TITLE-ABS-KEY("Dexamethasone") OR TITLE-ABS- 35 KEY("Methylfluorprednisolone") OR TITLE-ABS- KEY("Hexadecadrol") OR TITLE-ABS-KEY("Decameth") OR TITLE- ABS-KEY("Decaspray") OR TITLE-ABS-KEY("Dexasone") OR TITLE-ABS-KEY("Dexpak") OR TITLE-ABS-KEY("Maxidex") OR TITLE-ABS-KEY("Millicorten") OR TITLE-ABS-KEY("Oradexon") OR TITLE-ABS-KEY("Decaject") OR TITLE-ABS-KEY("Hexadrol")) #16 Diacerein (TITLE-ABS-KEY("Diacerein") OR TITLE-ABS-KEY("Diacerhein") 66 OR TITLE-ABS-KEY("Diacetylrhein") OR TITLE-ABS-KEY("Diacetyl- rhein") OR TITLE-ABS-KEY("Zondar")) #17 Diclofenac (TITLE-ABS-KEY("Diclofenac") OR TITLE-ABS-KEY("Diclophenac") 423 OR TITLE-ABS-KEY("Dicrofenac") OR TITLE-ABS- KEY("Dichlofenal") OR TITLE-ABS-KEY("Diclonate P") OR TITLE- ABS-KEY("Feloran") OR TITLE-ABS-KEY("Voltarol") OR TITLE- ABS-KEY("Novapirina") OR TITLE-ABS-KEY("Orthofen") OR TITLE- ABS-KEY("Ortofen") OR TITLE-ABS-KEY("Orthophen") OR TITLE- ABS-KEY("Voltaren")) #18 Diflunisal (TITLE-ABS-KEY("Diflunisal") OR TITLE-ABS-KEY("Dolobid") OR 14 TITLE-ABS-KEY("Dolocid") OR TITLE-ABS-KEY("Dolobis") OR TITLE-ABS-KEY("NuDifunisal") OR TITLE-ABS- KEY("NovoDiflunisal") OR TITLE-ABS-KEY("ApoDiflunisal")) #19 Doxycycline (TITLE-ABS-KEY("Doxycycline") OR TITLE-ABS-KEY("Alpha-6- 35 Deoxyoxytetracycline") OR TITLE-ABS-KEY("Alpha 6 Deoxyoxytetracycline") OR TITLE-ABS-KEY("Oracea") OR TITLE- ABS-KEY("Periostat") OR TITLE-ABS-KEY("Vibra-Tabs") OR TITLE- ABS-KEY("Vibra Tabs") OR TITLE-ABS-KEY("VibraTabs") OR TITLE- ABS-KEY("Vibramycin") OR TITLE-ABS-KEY("Vibravenos") OR TITLE-ABS-KEY("Atridox") OR TITLE-ABS-KEY("Doryx") OR TITLE- ABS-KEY("Hydramycin")) #20 Duloxetine (TITLE-ABS-KEY("Duloxetine") OR TITLE-ABS-KEY("Propanamide") 44 OR TITLE-ABS-KEY("Cymbalta")) #21 Eltenac (TITLE-ABS-KEY("Eltenac") OR TITLE-ABS-KEY("Telzenac")) 5

#22 Etodolac (TITLE-ABS-KEY("Etodolac") OR TITLE-ABS-KEY("Etodolic Acid") 37 OR TITLE-ABS-KEY("Ultradol") OR TITLE-ABS-KEY("Lodine") OR TITLE-ABS-KEY("Ramodar")) #23 Etoricoxib (TITLE-ABS-KEY("Etoricoxib") OR TITLE-ABS-KEY("Arcoxia")) 50 #24 Fentanyl (TITLE-ABS-KEY("Fentanyl") OR TITLE-ABS-KEY("Phentanyl") OR 44 TITLE-ABS-KEY("Fentanest") OR TITLE-ABS-KEY("Sublimaze") OR TITLE-ABS-KEY("Duragesic") OR TITLE-ABS-KEY("Durogesic") OR TITLE-ABS-KEY("Fentora")) #25 Flurbiprofen (TITLE-ABS-KEY("Flurbiprofen") OR TITLE-ABS-KEY("Flubiprofen") 34 OR TITLE-ABS-KEY("Fluriproben") OR TITLE-ABS-KEY("Cebutid") OR TITLE-ABS-KEY("Dobrofen") OR TITLE-ABS-KEY("Flugalin") OR TITLE-ABS-KEY("Froben") OR TITLE-ABS-KEY("Neo Artrol") OR TITLE-ABS-KEY("Ocufen") OR TITLE-ABS-KEY("Ocuflur") OR TITLE-ABS-KEY("Strefen") OR TITLE-ABS-KEY("Ansaid")) #26 Corticosteroids (TITLE-ABS-KEY("Adrenal Cortex Hormones") OR TITLE-ABS- 306 KEY("Corticosteroid") OR TITLE-ABS-KEY("Corticosteroids") OR TITLE-ABS-KEY("Corticoid") OR TITLE-ABS-KEY("Corticoids")) #27 Glucosamine (TITLE-ABS-KEY("Glucosamine") OR TITLE-ABS- 357 KEY("Hespercorbin") OR TITLE-ABS-KEY("Dona") OR TITLE-ABS- KEY("Xicil"))

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #28 Hyaluronic acid (TITLE-ABS-KEY("Hyaluronic Acid") OR TITLE-ABS-KEY("Amo 594 Vitrax") OR TITLE-ABS-KEY("Biolon") OR TITLE-ABS- KEY("Etamucine") OR TITLE-ABS-KEY("Hyaluronan") OR TITLE- ABS-KEY("Hyvisc") OR TITLE-ABS-KEY("Luronit") OR TITLE-ABS- KEY("Hyaluronate") OR TITLE-ABS-KEY("Amvisc") OR TITLE-ABS- KEY("Healon") OR TITLE-ABS-KEY("Synvisc") OR TITLE-ABS- KEY("Orthovisc") OR TITLE-ABS-KEY("Hyalectin") OR TITLE-ABS- KEY("Hyalgan") OR TITLE-ABS-KEY("Vitrax") OR TITLE-ABS- KEY("Ostenil") OR TITLE-ABS-KEY("Hylan") OR TITLE-ABS- KEY("Suplasyn") OR TITLE-ABS-KEY("Arthrum") OR TITLE-ABS- KEY("Go-on") OR TITLE-ABS-KEY("Hyalart") OR TITLE-ABS- KEY("Nuflexxa") OR TITLE-ABS-KEY("Replasyn") OR TITLE-ABS- KEY("Durolane") OR TITLE-ABS-KEY("Supartz")) #29 Hydrocortisone (TITLE-ABS-KEY("Hydrocortisone") OR TITLE-ABS-KEY("Cortisol") 24 OR TITLE-ABS-KEY("Epicortisol") OR TITLE-ABS-KEY("Cortifair") OR TITLE-ABS-KEY("Cortril")) #30 Ibuprofen (TITLE-ABS-KEY("Ibuprofen") OR TITLE-ABS-KEY("Ibumetin") OR 247 TITLE-ABS-KEY("IP-82") OR TITLE-ABS-KEY("IP 82") OR TITLE- ABS-KEY("IP82") OR TITLE-ABS-KEY("Motrin") OR TITLE-ABS- KEY("Nuprin") OR TITLE-ABS-KEY("Rufen") OR TITLE-ABS- KEY("Salprofen") OR TITLE-ABS-KEY("Trauma-Dolgit Gel") OR TITLE-ABS-KEY("Trauma Dolgit Gel") OR TITLE-ABS- KEY("TraumaDolgit Gel") OR TITLE-ABS-KEY("Brufen")) #31 Indomethacin (TITLE-ABS-KEY("Indomethacin") OR TITLE-ABS- 81 KEY("Indometacin") OR TITLE-ABS-KEY("Amuno") OR TITLE-ABS- KEY("Indocid") OR TITLE-ABS-KEY("Metindol") OR TITLE-ABS- KEY("Indomet 140") OR TITLE-ABS-KEY("Osmosin") OR TITLE- ABS-KEY("Indocin")) #32 Ketoprofen (TITLE-ABS-KEY("Ketoprofen") OR TITLE-ABS- 55 KEY("Benzoylhydratropic Acid") OR TITLE-ABS-KEY("Profenid") OR TITLE-ABS-KEY("Alrheumum") OR TITLE-ABS-KEY("Orudis") OR TITLE-ABS-KEY("Alrheumat")) #33 Ketorolac (TITLE-ABS-KEY("Ketorolac") OR TITLE-ABS-KEY("Acular") OR 37 TITLE-ABS-KEY("Toradol")) #34 Licofelone (TITLE-ABS-KEY("Licofelone")) 8 #35 Lornoxicam (TITLE-ABS-KEY("Lornoxicam") OR TITLE-ABS- 11 KEY("Chlortenoxicam") OR TITLE-ABS-KEY("Xefocam")) #36 Lumiracoxib (TITLE-ABS-KEY("Lumiracoxib") OR TITLE-ABS-KEY("Prexige")) 29 #37 MMP Inhibitors (TITLE-ABS-KEY("Matrix Metalloproteinase Inhibitors") OR TITLE- 11 ABS-KEY("Matrix Metalloproteinase Inhibitor") OR TITLE-ABS- KEY("MMP Inhibitors") OR TITLE-ABS-KEY("MMP Inhibitor") OR TITLE-ABS-KEY("Stromelysin Inhibitors") OR TITLE-ABS- KEY("Stromelysin Inhibitor") OR TITLE-ABS-KEY("Gelatinase Inhibitors") OR TITLE-ABS-KEY("Gelatinase Inhibitor") OR TITLE- ABS-KEY("Collagenase Inhibitors") OR TITLE-ABS- KEY("Collagenase Inhibitor")) #38 Meloxicam (TITLE-ABS-KEY("Meloxicam") OR TITLE-ABS-KEY("Reumoxicam") 60 OR TITLE-ABS-KEY("Miloxicam") OR TITLE-ABS-KEY("Movalis") OR TITLE-ABS-KEY("Uticox") OR TITLE-ABS-KEY("Mobic") OR TITLE- ABS-KEY("Mobicox") OR TITLE-ABS-KEY("Mobec") OR TITLE-ABS- KEY("Masflex") OR TITLE-ABS-KEY("Movicox") OR TITLE-ABS- KEY("Parocin")) #39 Metamizole (TITLE-ABS-KEY("Metamizole") OR TITLE-ABS-KEY("Dipyrone") OR 5 TITLE-ABS-KEY("Noramidopyrine Methanesulfonate Sodium") OR TITLE-ABS-KEY("Metamizol") OR TITLE-ABS-KEY("Methamizole") OR TITLE-ABS-KEY("Dipyronium") OR TITLE-ABS- KEY("Methampyrone") OR TITLE-ABS-KEY("Novaminsulfone") OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records TITLE-ABS-KEY("Sulpyrin") OR TITLE-ABS-KEY("Sulpyrine") OR TITLE-ABS-KEY("Optalgin") OR TITLE-ABS-KEY("Novalgin") OR TITLE-ABS-KEY("Analgin") OR TITLE-ABS-KEY("Narone") OR TITLE-ABS-KEY("Biopyrin") OR TITLE-ABS-KEY("Noramidopyrine Methanesulfonate") OR TITLE-ABS-KEY("Normelubrine") OR TITLE- ABS-KEY("Novalgetol") OR TITLE-ABS-KEY("Pyralgin") OR TITLE- ABS-KEY("Algopyrin")) #40 Methylprednisolone (TITLE-ABS-KEY("Methylprednisolone") OR TITLE-ABS- 95 KEY("Metipred") OR TITLE-ABS-KEY("Urbason") OR TITLE-ABS- KEY("Medrol") OR TITLE-ABS-KEY("UrbasonSoluble") OR TITLE- ABS-KEY("SoluMedrol") OR TITLE-ABS-KEY("A-MethaPred")) #41 Methylsulfonylmethane (TITLE-ABS-KEY("Dimethyl Sulfone") OR TITLE-ABS-KEY("Methyl 22 Sulfonmethane") OR TITLE-ABS-KEY("Methylsulfonylmethane") OR TITLE-ABS-KEY("Methyl Sulfone")) #42 Nabumetone (TITLE-ABS-KEY("Nabumetone") OR TITLE-ABS-KEY("Nabumeton") 44 OR TITLE-ABS-KEY("Arthraxan") OR TITLE-ABS-KEY("Listran") OR TITLE-ABS-KEY("Relafen") OR TITLE-ABS-KEY("Relif") OR TITLE- ABS-KEY("Relifex") OR TITLE-ABS-KEY("Mebutan") OR TITLE-ABS- KEY("Nabucox")) #43 Naproxcinod (TITLE-ABS-KEY("Naproxcinod") OR TITLE-ABS-KEY("NO- 9 naproxen") OR TITLE-ABS-KEY("Nitric Oxide Naproxen") OR TITLE- ABS-KEY("NicOx")) #44 Naproxen (TITLE-ABS-KEY("Naproxen") OR TITLE-ABS- 229 KEY("Methoxypropiocin") OR TITLE-ABS-KEY("MNPA") OR TITLE- ABS-KEY("Anaprox") OR TITLE-ABS-KEY("Naprosin") OR TITLE- ABS-KEY("Naprosyn") OR TITLE-ABS-KEY("Proxen") OR TITLE- ABS-KEY("Synflex") OR TITLE-ABS-KEY("Aleve")) #45 Nimesulide (TITLE-ABS-KEY("Nimesulide") OR TITLE-ABS-KEY("Aulin") OR 28 TITLE-ABS-KEY("Eskaflam") OR TITLE-ABS-KEY("lizepat") OR TITLE-ABS-KEY("Mesulid") OR TITLE-ABS-KEY("Nexen") OR TITLE- ABS-KEY("Nimesil") OR TITLE-ABS-KEY("Redaflam") OR TITLE- ABS-KEY("Antifloxil") OR TITLE-ABS-KEY("Guaxan")) #46 Opioids (TITLE-ABS-KEY("Opioid Analgesics") OR TITLE-ABS-KEY("Opioid 186 Analgesic") OR TITLE-ABS-KEY("Opioids") OR TITLE-ABS- KEY("Opioid")) #47 Oxaprozin (TITLE-ABS-KEY("Oxaprozin") OR TITLE-ABS-KEY("Danoprox") OR 13 TITLE-ABS-KEY("Dayrun") OR TITLE-ABS-KEY("Daypro")) #48 Parecoxib (TITLE-ABS-KEY("Parecoxib") OR TITLE-ABS-KEY("Dynastat")) 8 #49 Pennsaid (TITLE-ABS-KEY("Pennsaid")) 12 #50 Piroxicam (TITLE-ABS-KEY("Piroxicam") OR TITLE-ABS-KEY("Feldene")) 116 #51 Prednisolone (TITLE-ABS-KEY("Prednisolone") OR TITLE-ABS-KEY("Predate") OR 25 TITLE-ABS-KEY("Predonine") OR TITLE-ABS-KEY("Di-Adreson-F") OR TITLE-ABS-KEY("DiAdreson F") OR TITLE-ABS- KEY("DiAdresonF")) #52 Risedronate (TITLE-ABS-KEY("Risedronate") OR TITLE-ABS-KEY("Risedronic 25 Acid") OR TITLE-ABS-KEY("Actonel") OR TITLE-ABS-KEY("Atelvia")) #53 Rofecoxib (TITLE-ABS-KEY("Rofecoxib") OR TITLE-ABS-KEY("Vioxx")) 108 #54 SAME (TITLE-ABS-KEY("S-Adenosylmethionine") OR TITLE-ABS- 489 KEY("SAME") OR TITLE-ABS-KEY("SAM-e") OR TITLE-ABS- KEY("AdoMet") OR TITLE-ABS-KEY("S-Adenosyl-L-Methionine") OR TITLE-ABS-KEY("S Adenosyl L Methionine") OR TITLE-ABS- KEY("Ademetionine") OR TITLE-ABS-KEY("S Amet") OR TITLE-ABS- KEY("Samyr") OR TITLE-ABS-KEY("Gumbaral")) #55 Sprifermin (TITLE-ABS-KEY("Fibroblast Growth Factor 18") OR TITLE-ABS- 9 KEY("Sprifermin"))

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #56 Steroids (TITLE-ABS-KEY("Steroid") OR TITLE-ABS-KEY("Steroids")) 144 #57 Strontium ranelate (TITLE-ABS-KEY("Strontium Ranelate") OR TITLE-ABS- 25 KEY("Protelos")) #58 Sulindac (TITLE-ABS-KEY("Sulindac") OR TITLE-ABS-KEY("Apo-Sulin") OR 21 TITLE-ABS-KEY("Apo Sulin") OR TITLE-ABS-KEY("Arthrobid") OR TITLE-ABS-KEY("Clinoril") OR TITLE-ABS-KEY("Arthrocine") OR TITLE-ABS-KEY("Klinoril") OR TITLE-ABS-KEY("Sulindal") OR TITLE-ABS-KEY("Chibret") OR TITLE-ABS-KEY("Kenalin") OR TITLE-ABS-KEY("Novo-Sundac") OR TITLE-ABS-KEY("Novo Sundac") OR TITLE-ABS-KEY("Aclin") OR TITLE-ABS-KEY("Copal")) #59 Tenidap (TITLE-ABS-KEY("Tenidap")) 3 #60 Tenoxicam (TITLE-ABS-KEY("Tenoxicam") OR TITLE-ABS-KEY("Reutenox") OR 28 TITLE-ABS-KEY("Artriunic") OR TITLE-ABS-KEY("Mobiflex") OR TITLE-ABS-KEY("Tilcotil")) #61 Tiaprofenic acid (TITLE-ABS-KEY("Tiaprofenic Acid") OR TITLE-ABS-KEY("Flanid") 17 OR TITLE-ABS-KEY("Nu-Tiaprofenic") OR TITLE-ABS-KEY("PMS- Tiaprofenic") OR TITLE-ABS-KEY("Surgam") OR TITLE-ABS- KEY("Apo-Tiaprofenic") OR TITLE-ABS-KEY("Novo-Tiaprofenic")) #62 Tolmetin-Na (TITLE-ABS-KEY("Tolmetin") OR TITLE-ABS-KEY("Tolectin")) 1 #63 Tramadol (TITLE-ABS-KEY("Tramadol") OR TITLE-ABS-KEY("Tramundin") OR 126 TITLE-ABS-KEY("Biodalgic") OR TITLE-ABS-KEY("Jutadol") OR TITLE-ABS-KEY("Nobligan") OR TITLE-ABS-KEY("Prontofort") OR TITLE-ABS-KEY("Zytram") OR TITLE-ABS-KEY("Takadol") OR TITLE-ABS-KEY("Theradol") OR TITLE-ABS-KEY("Tiral") OR TITLE- ABS-KEY("Topalgic") OR TITLE-ABS-KEY("Tradol") OR TITLE-ABS- KEY("TradolPuren") OR TITLE-ABS-KEY("Tradonal") OR TITLE-ABS- KEY("Tralgiol") OR TITLE-ABS-KEY("Trama") OR TITLE-ABS- KEY("TramaDorsch") OR TITLE-ABS-KEY("Biokanol") OR TITLE- ABS-KEY("Tramabeta") OR TITLE-ABS-KEY("Tramadin") OR TITLE- ABS-KEY("Tramadolratiopharm") OR TITLE-ABS-KEY("Tramadoc") OR TITLE-ABS-KEY("Ranitidin 1A Pharma") OR TITLE-ABS- KEY("Trasedal") OR TITLE-ABS-KEY("Ultram") OR TITLE-ABS- KEY("Xymel 50") OR TITLE-ABS-KEY("Zamudol") OR TITLE-ABS- KEY("Zydol") OR TITLE-ABS-KEY("TramadolDolgit") OR TITLE-ABS- KEY("TramadolHameln") OR TITLE-ABS-KEY("Tramadolor") OR TITLE-ABS-KEY("Tramadura") OR TITLE-ABS-KEY("Tramagetic") OR TITLE-ABS-KEY("Tramagit") OR TITLE-ABS-KEY("Tramake") OR TITLE-ABS-KEY("Tramal") OR TITLE-ABS-KEY("Tramex") OR TITLE-ABS-KEY("Adolonta") OR TITLE-ABS-KEY("Contramal") OR TITLE-ABS-KEY("Amadol")) #64 Triamcinolone (TITLE-ABS-KEY("Triamcinolone") OR TITLE-ABS-KEY("Volon") OR 126 TITLE-ABS-KEY("Aristocort")) #65 Trolamine salicylate (TITLE-ABS-KEY("Trolamine Salicylate") OR TITLE-ABS- 6 KEY("Triethanolamine Salicylate") OR TITLE-ABS-KEY("Myoflex")) #66 Valdecoxib (TITLE-ABS-KEY("Valdecoxib") OR TITLE-ABS-KEY("Bextra")) 25 #67 Vitamin D (TITLE-ABS-KEY("Vitamin D")) 64 #68 Vitamin E (TITLE-ABS-KEY("Vitamin E")) 16 #69 Zoledronic acid (TITLE-ABS-KEY("Zoledronic Acid") OR TITLE-ABS- 14 KEY("Zoledronate") OR TITLE-ABS-KEY("Zometa")) #70 Final query #1 AND #2 AND (#3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR 1364 Limit to KEY(Knee #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR Osteoarthrtitis) AND #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR KEY(Randomised #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR Controlled Trial) #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69)

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 489 eTable 1C - Final search strategy for Embase #ID Topic or intervention Query Records #1 Disease 'knee osteoarthritis'/exp OR ('osteoarthritis'/exp AND 'knee'/exp) OR 56723 (osteoarthrit*:ab,ti,kw OR arthrit*:ab,ti,kw OR 'osteo arthrit*':ti,ab,kw) AND knee*:ti,ab,kw OR'knee oa':ti,ab,kw OR 'knees oa':ti,ab,kw

#2 Study design 'randomized controlled trial'/exp OR 'randomized controlled trial':ti,ab,it 935946 OR 'randomized':ti,ab,it OR 'randomised':ti,ab,it OR 'randomization':ti,ab,it OR 'randomisation':ti,ab,it OR rct:ti,ab,it

#3 Aceclofenac aceclofenac'/exp/mj OR 'aceclofenac':ab,ti OR 'falcol':ab,ti OR 'clanza 20 cr':ab,ti OR 'preservex':ab,ti OR 'biofenac':ab,ti OR 'sanein':ab,ti OR 'beofenac':ab,ti OR 'aital':ab,ti OR 'airtal':ab,ti OR 'bristaflam':ab,ti OR 'gerbin':ab,ti #4 Acetaminophen paracetamol'/exp/mj OR 'paracetamol':ab,ti OR 342 'hydroxyacetanilide':ab,ti OR 'APAP':ab,ti OR 'acetamidophenol':ab,ti OR 'acetaminophen':ab,ti OR 'acephen':ab,ti OR 'acetaco':ab,ti OR 'tylenol':ab,ti OR 'anacin-3':ab,ti OR 'anacin 3':ab,ti OR 'anacin3':ab,ti OR 'datril':ab,ti OR 'panadol':ab,ti OR 'acamol':ab,ti OR 'algotropyl':ab,ti #5 Androstenedione androstenedione'/exp/mj OR 'androstenedione':ab,ti OR 0 'androstene':ab,ti #6 ASA acetylsalicylic acid'/exp/mj OR 'aspirin':ab,ti OR 'acetylsalicylic 38 acid':ab,ti OR 'acylpyrin':ab,ti OR 'aloxiprimum':ab,ti OR 'colfarit':ab,ti OR 'dispril':ab,ti OR 'easprin':ab,ti OR 'ecotrin':ab,ti OR 'endosprin':ab,ti OR 'magnecyl':ab,ti OR 'micristin':ab,ti OR 'polopirin':ab,ti OR 'polopiryna':ab,ti OR 'solprin':ab,ti OR 'solupsan':ab,ti OR 'zorprin':ab,ti OR 'acetysal':ab,ti #7 Benoxaprofen benoxaprofen'/exp/mj OR 'benoxaprofen':ab,ti OR 'oraflex':ab,ti 1 #8 Betamethasone betamethasone'/exp/mj OR 'betamethasone':ab,ti OR 19 'flubenisolone':ab,ti OR 'betadexamethasone':ab,ti OR 'celestona':ab,ti OR 'cellestoderm':ab,ti OR 'celeston':ab,ti OR 'celestone':ab,ti #9 Calcitonin calcitonin'/exp/mj OR 'calcitonin':ab,ti OR 'calcitrin':ab,ti OR 29 'thyrocalcitonin':ab,ti OR 'ciba 47175-ba':ab,ti OR 'ciba 47175 ba':ab,ti OR 'ciba 47175ba':ab,ti #10 Capsaicin capsaicin'/exp/mj OR 'capsaicin':ab,ti OR 'capsaicine':ab,ti OR 23 'axsain':ab,ti OR 'zacin':ab,ti OR 'capsidol':ab,ti OR 'zostrix':ab,ti OR 'capzasin':ab,ti OR 'gelcen':ab,ti OR 'katrum':ab,ti OR 'capsicum farmaya':ab,ti OR 'capsin':ab,ti #11 Celecoxib celecoxib'/exp/mj OR 'celecoxib':ab,ti OR 'celebrex':ab,ti 196 #12 Chondroitin chondroitin sulfate'/exp/mj OR 'chondroitin sulfate':ab,ti OR 228 'chondroitin':ab,ti OR 'chonsurid':ab,ti OR 'translagen':ab,ti OR 'blutal':ab,ti #13 Cindunistat cindunistat'/exp/mj OR 'cindunistat':ab,ti 2 #14 Cortivazol cortivazol'/exp/mj OR 'cortivazol':ab,ti 2 #15 Dexamethasone dexamethasone'/exp/mj OR 'dexamethasone':ab,ti OR 23 'methylfluorprednisolone':ab,ti OR 'hexadecadrol':ab,ti OR 'decameth':ab,ti OR 'decaspray':ab,ti OR 'dexasone':ab,ti OR 'dexpak':ab,ti OR 'maxidex':ab,ti OR 'millicorten':ab,ti OR 'oradexon':ab,ti OR 'decaject':ab,ti OR 'hexadrol':ab,ti #16 Diacerein diacerein'/exp/mj OR 'diacerein':ab,ti OR 'diacerhein':ab,ti OR 42 'diacetylrhein':ab,ti OR 'diacetyl-rhein':ab,ti OR 'zondar':ab,ti #17 Diclofenac diclofenac'/exp/mj OR 'diclofenac':ab,ti OR 'diclophenac':ab,ti OR 242 'dicrofenac':ab,ti OR 'dichlofenal':ab,ti OR 'diclonate p':ab,ti OR 'feloran':ab,ti OR 'voltarol':ab,ti OR 'novapirina':ab,ti OR 'orthofen':ab,ti

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records OR 'ortofen':ab,ti OR 'orthophen':ab,ti OR 'voltaren':ab,ti #18 Diflunisal diflunisal'/exp/mj OR 'diflunisal':ab,ti OR 'dolobid':ab,ti OR 7 'dolocid':ab,ti OR 'dolobis':ab,ti OR 'nudifunisal':ab,ti OR 'novodiflunisal':ab,ti OR 'apodiflunisal':ab,ti #19 Doxycycline doxycycline'/exp/mj OR 'doxycycline':ab,ti OR 'alpha-6- 21 deoxyoxytetracycline':ab,ti OR 'alpha 6 deoxyoxytetracycline':ab,ti OR 'oracea':ab,ti OR 'periostat':ab,ti OR 'vibra-tabs':ab,ti OR 'vibra tabs':ab,ti OR 'vibratabs':ab,ti OR 'vibramycin':ab,ti OR 'vibravenos':ab,ti OR 'atridox':ab,ti OR 'doryx':ab,ti OR 'hydramycin':ab,ti #20 Duloxetine duloxetine'/exp/mj OR 'duloxetine':ab,ti OR 'propanamide':ab,ti OR 36 'cymbalta':ab,ti #21 Eltenac eltenac'/exp/mj OR 'eltenac':ab,ti OR 'telzenac':ab,ti 2 #22 Etodolac etodolac'/exp/mj OR 'etodolac':ab,ti OR 'etodolic acid':ab,ti OR 20 'ultradol':ab,ti OR 'lodine':ab,ti OR 'ramodar':ab,ti #23 Etoricoxib etoricoxib'/exp/mj OR 'etoricoxib':ab,ti OR 'arcoxia':ab,ti 34 #24 Fentanyl fentanyl'/exp/mj OR 'fentanyl':ab,ti OR 'phentanyl':ab,ti OR 12 'fentanest':ab,ti OR 'sublimaze':ab,ti OR 'duragesic':ab,ti OR 'durogesic':ab,ti OR 'fentora':ab,ti #25 Flurbiprofen flurbiprofen'/exp/mj OR 'flurbiprofen':ab,ti OR 'flubiprofen':ab,ti OR 13 'fluriproben':ab,ti OR 'cebutid':ab,ti OR 'dobrofen':ab,ti OR 'flugalin':ab,ti OR 'froben':ab,ti OR 'neo artrol':ab,ti OR 'ocufen':ab,ti OR 'ocuflur':ab,ti OR 'strefen':ab,ti OR 'ansaid':ab,ti #26 corticosteroids corticosteroid'/exp/mj OR 'adrenal cortex hormones':ab,ti OR 285 'corticosteroid':ab,ti OR 'corticosteroids':ab,ti OR 'corticoid':ab,ti OR 'corticoids':ab,ti #27 Glucosamine glucosamine'/exp/mj OR 'glucosamine':ab,ti OR 'hespercorbin':ab,ti 279 OR 'dona':ab,ti OR 'xicil':ab,ti #28 Hyaluronic acid hyaluronic acid'/exp/mj OR 'hyaluronic acid':ab,ti OR 'amo vitrax':ab,ti 556 OR 'biolon':ab,ti OR 'etamucine':ab,ti OR 'hyaluronan':ab,ti OR 'hyvisc':ab,ti OR 'luronit':ab,ti OR 'hyaluronate':ab,ti OR 'amvisc':ab,ti OR 'healon':ab,ti OR 'synvisc':ab,ti OR 'orthovisc':ab,ti OR 'hyalectin':ab,ti OR 'hyalgan':ab,ti OR 'vitrax':ab,ti OR 'ostenil':ab,ti OR 'hylan':ab,ti OR 'suplasyn':ab,ti OR 'arthrum':ab,ti OR 'go-on':ab,ti OR 'hyalart':ab,ti OR 'nuflexxa':ab,ti OR 'replasyn':ab,ti OR 'durolane':ab,ti OR 'supartz':ab,ti #29 Hydrocortisone hydrocortisone'/exp/mj OR 'hydrocortisone':ab,ti OR 'cortisol':ab,ti OR 14 'epicortisol':ab,ti OR 'cortifair':ab,ti OR 'cortril':ab,ti #30 Ibuprofen ibuprofen'/exp/mj OR 'ibuprofen':ab,ti OR 'ibumetin':ab,ti OR 'ip- 112 82':ab,ti OR 'ip 82':ab,ti OR 'ip82':ab,ti OR 'motrin':ab,ti OR 'nuprin':ab,ti OR 'rufen':ab,ti OR 'salprofen':ab,ti OR 'trauma-dolgit gel':ab,ti OR 'trauma dolgit gel':ab,ti OR 'traumadolgit gel':ab,ti OR 'brufen':ab,ti #31 Indomethacin indometacin'/exp/mj OR 'indomethacin':ab,ti OR 'indometacin':ab,ti 28 OR 'amuno':ab,ti OR 'indocid':ab,ti OR 'metindol':ab,ti OR 'indomet 140':ab,ti OR 'osmosin':ab,ti OR 'indocin':ab,ti #32 Ketoprofen ketoprofen'/exp/mj OR 'ketoprofen':ab,ti OR 'benzoylhydratropic 23 acid':ab,ti OR 'profenid':ab,ti OR 'alrheumum':ab,ti OR 'orudis':ab,ti OR 'alrheumat':ab,ti #33 Ketorolac ketorolac'/exp/mj OR 'ketorolac':ab,ti OR 'acular':ab,ti OR 'toradol':ab,ti 14 #34 Licofelone licofelone'/exp/mj OR 'licofelone':ab,ti 8 #35 Lornoxicam lornoxicam'/exp/mj OR 'lornoxicam':ab,ti OR 'chlortenoxicam':ab,ti OR 10 'xefocam':ab,ti #36 Lumiracoxib lumiracoxib'/exp/mj OR 'lumiracoxib':ab,ti OR 'prexige':ab,ti 15

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #37 MMP Inhibitors matrix metalloproteinase inhibitor'/exp/mj OR 'matrix 7 metalloproteinase inhibitors':ab,ti OR 'matrix metalloproteinase inhibitor':ab,ti OR 'mmp inhibitors':ab,ti OR 'mmp inhibitor':ab,ti OR 'stromelysin inhibitors':ab,ti OR 'stromelysin inhibitor':ab,ti OR 'gelatinase inhibitors':ab,ti OR 'gelatinase inhibitor':ab,ti OR 'collagenase inhibitors':ab,ti OR 'collagenase inhibitor':ab,ti #38 Meloxicam meloxicam'/exp/mj OR 'meloxicam':ab,ti OR 'reumoxicam':ab,ti OR 30 'miloxicam':ab,ti OR 'movalis':ab,ti OR 'uticox':ab,ti OR 'mobic':ab,ti OR 'mobicox':ab,ti OR 'mobec':ab,ti OR 'masflex':ab,ti OR 'movicox':ab,ti OR 'parocin':ab,ti #39 Metamizole dipyrone'/exp/mj OR 'metamizole':ab,ti OR 'dipyrone':ab,ti OR 2 'noramidopyrine methanesulfonate sodium':ab,ti OR 'metamizol':ab,ti OR 'methamizole':ab,ti OR 'dipyronium':ab,ti OR 'methampyrone':ab,ti OR 'novaminsulfone':ab,ti OR 'sulpyrin':ab,ti OR 'sulpyrine':ab,ti OR 'optalgin':ab,ti OR 'novalgin':ab,ti OR 'analgin':ab,ti OR 'narone':ab,ti OR 'biopyrin':ab,ti OR 'noramidopyrine methanesulfonate':ab,ti OR 'normelubrine':ab,ti OR 'novalgetol':ab,ti OR 'pyralgin':ab,ti OR 'algopyrin':ab,ti #40 Methylprednisolone methylprednisolone'/exp/mj OR 'methylprednisolone':ab,ti OR 70 'metipred':ab,ti OR 'urbason':ab,ti OR 'medrol':ab,ti OR 'urbasonsoluble':ab,ti OR 'solumedrol':ab,ti OR 'a-methapred':ab,ti #41 Methylsulfonylmethane dimethyl sulfone'/exp/mj OR 'dimethyl sulfone':ab,ti OR 'methyl 19 sulfonmethane':ab,ti OR 'methylsulfonylmethane':ab,ti OR 'methyl sulfone':ab,ti #42 Nabumetone nabumetone'/exp/mj OR 'nabumetone':ab,ti OR 'nabumeton':ab,ti OR 24 'arthraxan':ab,ti OR 'listran':ab,ti OR 'relafen':ab,ti OR 'relif':ab,ti OR 'relifex':ab,ti OR 'mebutan':ab,ti OR 'nabucox':ab,ti #43 Naproxcinod naproxen-n-butyl nitrate' OR 'naproxcinod':ab,ti OR 'no-naproxen':ab,ti 12 OR 'nitric oxide naproxen':ab,ti OR 'nicox':ab,ti #44 Naproxen naproxen'/exp/mj OR 'naproxen':ab,ti OR 'methoxypropiocin':ab,ti OR 150 'mnpa':ab,ti OR 'anaprox':ab,ti OR 'naprosin':ab,ti OR 'naprosyn':ab,ti OR 'proxen':ab,ti OR 'synflex':ab,ti OR 'aleve':ab,ti #45 Nimesulide nimesulide'/exp/mj OR 'nimesulide':ab,ti OR 'aulin':ab,ti OR 18 'eskaflam':ab,ti OR 'lizepat':ab,ti OR 'mesulid':ab,ti OR 'nexen':ab,ti OR 'nimesil':ab,ti OR 'redaflam':ab,ti OR 'antifloxil':ab,ti OR 'guaxan':ab,ti #46 Opioids opiate'/exp/mj OR 'opiate':ab,ti OR 'opioid analgesics':ab,ti OR 'opioid 147 analgesic':ab,ti OR 'opioids':ab,ti OR 'opioid':ab,ti #47 Oxaprozin oxaprozin'/exp/mj OR 'oxaprozin':ab,ti OR 'danoprox':ab,ti OR 6 'dayrun':ab,ti OR 'daypro':ab,ti #48 Parecoxib parecoxib'/exp/mj OR 'parecoxib':ab,ti OR 'dynastat':ab,ti 1 #49 Pennsaid pennsaid':ab,ti 7 #50 Piroxicam piroxicam'/exp/mj OR 'piroxicam':ab,ti OR 'feldene':ab,ti 60 #51 Prednisolone prednisolone'/exp/mj OR 'prednisolone':ab,ti OR 'predate':ab,ti OR 12 'predonine':ab,ti OR 'di-adreson-f':ab,ti OR 'diadreson f':ab,ti OR 'diadresonf':ab,ti #52 Risedronate risedronic acid'/exp/mj OR 'risedronate':ab,ti OR 'risedronic acid':ab,ti 15 OR 'actonel':ab,ti OR 'atelvia':ab,ti #53 Rofecoxib rofecoxib'/exp/mj OR 'rofecoxib':ab,ti OR 'vioxx':ab,ti 48 #54 SAME s adenosylmethionine'/exp/mj OR 's adenosylmethionine':ab,ti OR 550 'same':ab,ti OR 'sam-e':ab,ti OR 'adomet':ab,ti OR 's-adenosyl-l- methionine':ab,ti OR 's adenosyl l methionine':ab,ti OR 'ademetionine':ab,ti OR 's amet':ab,ti OR 'samyr':ab,ti OR 'gumbaral':ab,ti #55 Sprifermin sprifermin'/exp/mj OR 'fibroblast growth factor 18':ab,ti OR 14

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records 'sprifermin':ab,ti #56 Steroids steroid'/exp/mj OR 'steroid':ab,ti OR 'steroids':ab,ti 274 #57 Strontium ranelate strontium ranelate'/exp/mj OR 'strontium ranelate':ab,ti OR 57 'protelos':ab,ti #58 Sulindac sulindac'/exp/mj OR 'sulindac':ab,ti OR 'apo-sulin':ab,ti OR 'apo 6 sulin':ab,ti OR 'arthrobid':ab,ti OR 'clinoril':ab,ti OR 'arthrocine':ab,ti OR 'klinoril':ab,ti OR 'sulindal':ab,ti OR 'chibret':ab,ti OR 'kenalin':ab,ti OR 'novo-sundac':ab,ti OR 'novo sundac':ab,ti OR 'aclin':ab,ti OR 'copal':ab,ti #59 Tenidap tenidap'/exp/mj OR 'tenidap':ab,ti 3 #60 Tenoxicam tenoxicam'/exp/mj OR 'tenoxicam':ab,ti OR 'reutenox':ab,ti OR 17 'artriunic':ab,ti OR 'mobiflex':ab,ti OR 'tilcotil':ab,ti #61 Tiaprofenic acid tiaprofenic acid'/exp/mj OR 'tiaprofenic acid':ab,ti OR 'flanid':ab,ti OR 8 'nu-tiaprofenic':ab,ti OR 'pms-tiaprofenic':ab,ti OR 'surgam':ab,ti OR 'apo-tiaprofenic':ab,ti OR 'novo-tiaprofenic':ab,ti #62 Tolmetin-Na tolmetin'/exp/mj OR 'tolmetin':ab,ti OR 'tolectin':ab,ti 0 #63 Tramadol tramadol'/exp/mj OR 'tramadol':ab,ti OR 'tramundin':ab,ti OR 54 'biodalgic':ab,ti OR 'jutadol':ab,ti OR 'nobligan':ab,ti OR 'prontofort':ab,ti OR 'zytram':ab,ti OR 'takadol':ab,ti OR 'theradol':ab,ti OR 'tiral':ab,ti OR 'topalgic':ab,ti OR 'tradol':ab,ti OR 'tradolpuren':ab,ti OR 'tradonal':ab,ti OR 'tralgiol':ab,ti OR 'trama':ab,ti OR 'tramadorsch':ab,ti OR 'biokanol':ab,ti OR 'tramabeta':ab,ti OR 'tramadin':ab,ti OR 'tramadolratiopharm':ab,ti OR 'tramadoc':ab,ti OR 'ranitidin 1a pharma':ab,ti OR 'trasedal':ab,ti OR 'ultram':ab,ti OR 'xymel 50':ab,ti OR 'zamudol':ab,ti OR 'zydol':ab,ti OR 'tramadoldolgit':ab,ti OR 'tramadolhameln':ab,ti OR 'tramadolor':ab,ti OR 'tramadura':ab,ti OR 'tramagetic':ab,ti OR 'tramagit':ab,ti OR 'tramake':ab,ti OR 'tramal':ab,ti OR 'tramex':ab,ti OR 'adolonta':ab,ti OR 'contramal':ab,ti OR 'amadol':ab,ti #64 Triamcinolone triamcinolone'/exp/mj OR 'triamcinolone':ab,ti OR 'volon':ab,ti OR 92 'aristocort':ab,ti #65 Trolamine salicylate triethanolamine salicylate'/exp/mj OR 'trolamine salicylate':ab,ti OR 2 'triethanolamine salicylate':ab,ti OR 'myoflex':ab,ti #66 Valdecoxib valdecoxib'/exp/mj OR 'valdecoxib':ab,ti OR 'bextra':ab,ti 6 #67 Vitamin D vitamin d'/exp/mj OR 'vitamin d':ab,ti 78 #68 Vitamin E alpha tocopherol'/exp/mj OR 'vitamin e':ab,ti 15 #69 Zoledronic acid zoledronic acid'/exp/mj OR 'zoledronic acid':ab,ti OR 12 'zoledronate':ab,ti OR 'zometa':ab,ti #70 Final query #1 AND #2 AND (#3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR 2482 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69) 490

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 491 eTable 1D - Final search strategy for Web of Science #ID Topic or intervention Query Records #1 Disease (TS=(knee osteoarthritis)) 37238 #2 Study design (TS=(Randomized controlled trial)) 405551 #3 Aceclofenac (TS=(aceclofenac) OR TS=(Falcol) OR TS=(Clanza CR) OR 13 TS=(Preservex) OR TS=(Biofenac) OR TS=(Sanein) OR TS=(Beofenac) OR TS=(Aital) OR TS=(Airtal) OR TS=(Bristaflam) OR TS=(Gerbin)) #4 Acetaminophen (TS=(Acetaminophen) OR TS=(Hydroxyacetanilide) OR TS=(APAP) 274 OR TS=(Acetamidophenol) OR TS=(Paracetamol) OR TS=(Acephen) OR TS=(Acetaco) OR TS=(Tylenol) OR TS=(Anacin- 3) OR TS=(Anacin 3) OR TS=(Anacin3) OR TS=(Datril) OR TS=(Panadol) OR TS=(Acamol) OR TS=(Algotropyl)) #5 Androstenedione (TS=(Androstenedione) OR TS=(Androstene)) 0 #6 ASA (TS=(Aspirin) OR TS=(Acetylsalicylic Acid) OR TS=(Acylpyrin) OR 29 TS=(Aloxiprimum) OR TS=(Colfarit) OR TS=(Dispril) OR TS=(Easprin) OR TS=(Ecotrin) OR TS=(Endosprin) OR TS=(Magnecyl) OR TS=(Micristin) OR TS=(Polopirin) OR TS=(Polopiryna) OR TS=(Solprin) OR TS=(Solupsan) OR TS=(Zorprin) OR TS=(Acetysal)) #7 Benoxaprofen (TS=(Benoxaprofen) OR TS=(Oraflex)) 0 #8 Betamethasone (TS=(Betamethasone) OR TS=(Flubenisolone) OR 11 TS=(Betadexamethasone) OR TS=(Celestona) OR TS=(Cellestoderm) OR TS=(Celeston) OR TS=(Celestone)) #9 Calcitonin (TS=(Calcitonin) OR TS=(Calcitrin) OR TS=(Thyrocalcitonin) OR 12 TS=(Ciba 47175-BA) OR TS=(Ciba 47175 BA) OR TS=(Ciba 47175BA)) #10 Capsaicin (TS=(Capsaicin) OR TS=(Capsaicine) OR TS=(Axsain) OR 38 TS=(Zacin) OR TS=(Capsidol) OR TS=(Zostrix) OR TS=(Capzasin) OR TS=(Gelcen) OR TS=(Katrum) OR TS=(Capsicum Farmaya) OR TS=(Capsin)) #11 Celecoxib (TS=(Celecoxib) OR TS=(Celebrex)) 177 #12 Chondroitin (TS=(Chondroitin Sulfate) OR TS=(Chondroitin) OR TS=(Chonsurid) 273 OR TS=(Translagen) OR TS=(Blutal)) #13 Cindunistat (TS=(Cindunistat)) 2 #14 Cortivazol (TS=(Cortivazol)) 1 #15 Dexamethasone (TS=(Dexamethasone) OR TS=(Methylfluorprednisolone) OR 12 TS=(Hexadecadrol) OR TS=(Decameth) OR TS=(Decaspray) OR TS=(Dexasone) OR TS=(Dexpak) OR TS=(Maxidex) OR TS=(Millicorten) OR TS=(Oradexon) OR TS=(Decaject) OR TS=(Hexadrol)) #16 Diacerein (TS=(Diacerein) OR TS=(Diacerhein) OR TS=(Diacetylrhein) OR 36 TS=(Diacetyl-rhein) OR TS=(Zondar)) #17 Diclofenac (TS=(Diclofenac) OR TS=(Diclophenac) OR TS=(Dicrofenac) OR 278 TS=(Dichlofenal) OR TS=(Diclonate P) OR TS=(Feloran) OR TS=(Voltarol) OR TS=(Novapirina) OR TS=(Orthofen) OR TS=(Ortofen) OR TS=(Orthophen) OR TS=(Voltaren)) #18 Diflunisal (TS=(Diflunisal) OR TS=(Dolobid) OR TS=(Dolocid) OR 1 TS=(Dolobis) OR TS=(NuDifunisal) OR TS=(NovoDiflunisal) OR TS=(ApoDiflunisal)) #19 Doxycycline (TS=(Doxycycline) OR TS=(Alpha-6-Deoxyoxytetracycline) OR 20 TS=(Alpha 6 Deoxyoxytetracycline) OR TS=(Oracea) OR TS=(Periostat) OR TS=(Vibra-Tabs) OR TS=(Vibra Tabs) OR TS=(VibraTabs) OR TS=(Vibramycin) OR TS=(Vibravenos) OR TS=(Atridox) OR TS=(Doryx) OR TS=(Hydramycin))

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records #20 Duloxetine (TS=(Duloxetine) OR TS=(Propanamide) OR TS=(Cymbalta)) 37 #21 Eltenac (TS=(Eltenac) OR TS=(Telzenac)) 1 #22 Etodolac (TS=(Etodolac) OR TS=(Etodolic Acid) OR TS=(Ultradol) OR 11 TS=(Lodine) OR TS=(Ramodar)) #23 Etoricoxib (TS=(Etoricoxib) OR TS=(Arcoxia)) 35 #24 Fentanyl (TS=(Fentanyl) OR TS=(Phentanyl) OR TS=(Fentanest) OR 17 TS=(Sublimaze) OR TS=(Duragesic) OR TS=(Durogesic) OR TS=(Fentora)) #25 Flurbiprofen (TS=(Flurbiprofen) OR TS=(Flubiprofen) OR TS=(Fluriproben) OR 10 TS=(Cebutid) OR TS=(Dobrofen) OR TS=(Flugalin) OR TS=(Froben) OR TS=(Neo Artrol) OR TS=(Ocufen) OR TS=(Ocuflur) OR TS=(Strefen) OR TS=(Ansaid)) #26 Corticosteroids (TS=(Adrenal Cortex Hormones) OR TS=(Corticosteroid) OR 228 TS=(Corticosteroids) OR TS=(Corticoid) OR TS=(Corticoids)) #27 Glucosamine (TS=(Glucosamine) OR TS=(Hespercorbin) OR TS=(Dona) OR 328 TS=(Xicil)) #28 Hyaluronic acid (TS=(Hyaluronic Acid) OR TS=(Amo Vitrax) OR TS=(Biolon) OR 529 TS=(Etamucine) OR TS=(Hyaluronan) OR TS=(Hyvisc) OR TS=(Luronit) OR TS=(Hyaluronate) OR TS=(Amvisc) OR TS=(Healon) OR TS=(Synvisc) OR TS=(Orthovisc) OR TS=(Hyalectin) OR TS=(Hyalgan) OR TS=(Vitrax) OR TS=(Ostenil) OR TS=(Hylan) OR TS=(Suplasyn) OR TS=(Arthrum) OR TS=(Go-on) OR TS=(Hyalart) OR TS=(Nuflexxa) OR TS=(Replasyn) OR TS=(Durolane) OR TS=(Supartz)) #29 Hydrocortisone (TS=(Hydrocortisone) OR TS=(Cortisol) OR TS=(Epicortisol) OR 10 TS=(Cortifair) OR TS=(Cortril)) #30 Ibuprofen (TS=(Ibuprofen) OR TS=(Ibumetin) OR TS=(IP-82) OR TS=(IP 82) 115 OR TS=(IP82) OR TS=(Motrin) OR TS=(Nuprin) OR TS=(Rufen) OR TS=(Salprofen) OR TS=(Trauma-Dolgit Gel) OR TS=(Trauma Dolgit Gel) OR TS=(TraumaDolgit Gel) OR TS=(Brufen)) #31 Indomethacin (TS=(Indomethacin) OR TS=(Indometacin) OR TS=(Amuno) OR 15 TS=(Indocid) OR TS=(Metindol) OR TS=(Indomet 140) OR TS=(Osmosin) OR TS=(Indocin)) #32 Ketoprofen (TS=(Ketoprofen) OR TS=(Benzoylhydratropic Acid) OR 23 TS=(Profenid) OR TS=(Alrheumum) OR TS=(Orudis) OR TS=(Alrheumat)) #33 Ketorolac (TS=(Ketorolac) OR TS=(Acular) OR TS=(Toradol)) 9 #34 Licofelone (TS=(Licofelone)) 1 #35 Lornoxicam (TS=(Lornoxicam) OR TS=(Chlortenoxicam) OR TS=(Xefocam)) 6 #36 Lumiracoxib (TS=(Lumiracoxib) OR TS=(Prexige)) 28 #37 MMP Inhibitors (TS=(Matrix Metalloproteinase Inhibitors) OR TS=(Matrix 16 Metalloproteinase Inhibitor) OR TS=(MMP Inhibitors) OR TS=(MMP Inhibitor) OR TS=(Stromelysin Inhibitors) OR TS=(Stromelysin Inhibitor) OR TS=(Gelatinase Inhibitors) OR TS=(Gelatinase Inhibitor) OR TS=(Collagenase Inhibitors) OR TS=(Collagenase Inhibitor)) #38 Meloxicam (TS=(Meloxicam) OR TS=(Reumoxicam) OR TS=(Miloxicam) OR 18 TS=(Movalis) OR TS=(Uticox) OR TS=(Mobic) OR TS=(Mobicox) OR TS=(Mobec) OR TS=(Masflex) OR TS=(Movicox) OR TS=(Parocin)) #39 Metamizole (TS=(Metamizole) OR TS=(Dipyrone) OR TS=(Noramidopyrine 0 Methanesulfonate Sodium) OR TS=(Metamizol) OR TS=(Methamizole) OR TS=(Dipyronium) OR TS=(Methampyrone) OR TS=(Novaminsulfone) OR TS=(Sulpyrin) OR TS=(Sulpyrine) OR TS=(Optalgin) OR TS=(Novalgin) OR TS=(Analgin) OR TS=(Narone) OR TS=(Biopyrin) OR TS=(Noramidopyrine Methanesulfonate) OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records TS=(Normelubrine) OR TS=(Novalgetol) OR TS=(Pyralgin) OR TS=(Algopyrin)) #40 Methylprednisolone (TS=(Methylprednisolone) OR TS=(Metipred) OR TS=(Urbason) OR 46 TS=(Medrol) OR TS=(UrbasonSoluble) OR TS=(SoluMedrol) OR TS=(A-MethaPred)) #41 Methylsulfonylmethane (TS=(Dimethyl Sulfone) OR TS=(Methyl Sulfonmethane) OR 23 TS=(Methylsulfonylmethane) OR TS=(Methyl Sulfone)) #42 Nabumetone (TS=(Nabumetone) OR TS=(Nabumeton) OR TS=(Arthraxan) OR 13 TS=(Listran) OR TS=(Relafen) OR TS=(Relif) OR TS=(Relifex) OR TS=(Mebutan) OR TS=(Nabucox)) #43 Naproxcinod (TS=(Naproxcinod) OR TS=(NO-naproxen) OR TS=(Nitric Oxide 5 Naproxen) OR TS=(NicOx)) #44 Naproxen (TS=(Naproxen) OR TS=(Methoxypropiocin) OR TS=(MNPA) OR 108 TS=(Anaprox) OR TS=(Naprosin) OR TS=(Naprosyn) OR TS=(Proxen) OR TS=(Synflex) OR TS=(Aleve)) #45 Nimesulide (TS=(Nimesulide) OR TS=(Aulin) OR TS=(Eskaflam) OR TS=(lizepat) 11 OR TS=(Mesulid) OR TS=(Nexen) OR TS=(Nimesil) OR TS=(Redaflam) OR TS=(Antifloxil) OR TS=(Guaxan)) #46 Opioids (TS=(Opioid Analgesics) OR TS=(Opioid Analgesic) OR TS=(Opioids) 180 OR TS=(Opioid)) #47 Oxaprozin (TS=(Oxaprozin) OR TS=(Danoprox) OR TS=(Dayrun) OR 3 TS=(Daypro)) #48 Parecoxib (TS=(Parecoxib) OR TS=(Dynastat)) 3 #49 Pennsaid (TS=(Pennsaid)) 9 #50 Piroxicam (TS=(Piroxicam) OR TS=(Feldene)) 35 #51 Prednisolone (TS=(Prednisolone) OR TS=(Predate) OR TS=(Predonine) OR 6 TS=(Di-Adreson-F) OR TS=(DiAdreson F) OR TS=(DiAdresonF)) #52 Risedronate (TS=(Risedronate) OR TS=(Risedronic Acid) OR TS=(Actonel) OR 19 TS=(Atelvia)) #53 Rofecoxib (TS=(Rofecoxib) OR TS=(Vioxx)) 77 #54 SAME (TS=(S-Adenosylmethionine) OR TS=("SAME") OR TS=(SAM-e) OR 309 TS=(AdoMet) OR TS=(S-Adenosyl-L-Methionine) OR TS=(S Adenosyl L Methionine) OR TS=(Ademetionine) OR TS=(S Amet) OR TS=(Samyr) OR TS=(Gumbaral)) #55 Sprifermin (TS=(Fibroblast Growth Factor 18) OR TS=(Sprifermin)) 13 #56 Steroids (TS=(Steroid) OR TS=(Steroids)) 155 #57 Strontium ranelate (TS=(Strontium Ranelate) OR TS=(Protelos)) 21 #58 Sulindac (TS=(Sulindac) OR TS=(Apo-Sulin) OR TS=(Apo Sulin) OR 0 TS=(Arthrobid) OR TS=(Clinoril) OR TS=(Arthrocine) OR TS=(Klinoril) OR TS=(Sulindal) OR TS=(Chibret) OR TS=(Kenalin) OR TS=(Novo- Sundac) OR TS=(Novo Sundac) OR TS=(Aclin) OR TS=(Copal)) #59 Tenidap (TS=(Tenidap)) 2 #60 Tenoxicam (TS=(Tenoxicam) OR TS=(Reutenox) OR TS=(Artriunic) OR 5 TS=(Mobiflex) OR TS=(Tilcotil)) #61 Tiaprofenic acid (TS=(Tiaprofenic Acid) OR TS=(Flanid) OR TS=(Nu-Tiaprofenic) OR 3 TS=(PMS-Tiaprofenic) OR TS=(Surgam) OR TS=(Apo-Tiaprofenic) OR TS=(Novo-Tiaprofenic)) #62 Tolmetin-Na (TS=(Tolmetin) OR TS=(Tolectin)) 0 #63 Tramadol (TS=(Tramadol) OR TS=(Tramundin) OR TS=(Biodalgic) OR 56 TS=(Jutadol) OR TS=(Nobligan) OR TS=(Prontofort) OR TS=(Zytram) OR TS=(Takadol) OR TS=(Theradol) OR TS=(Tiral) OR TS=(Topalgic) OR TS=(Tradol) OR TS=(TradolPuren) OR TS=(Tradonal) OR TS=(Tralgiol) OR TS=(Trama) OR

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 #ID Topic or intervention Query Records TS=(TramaDorsch) OR TS=(Biokanol) OR TS=(Tramabeta) OR TS=(Tramadin) OR TS=(Tramadolratiopharm) OR TS=(Tramadoc) OR TS=(Ranitidin 1A Pharma) OR TS=(Trasedal) OR TS=(Ultram) OR TS=(Xymel 50) OR TS=(Zamudol) OR TS=(Zydol) OR TS=(TramadolDolgit) OR TS=(TramadolHameln) OR TS=(Tramadolor) OR TS=(Tramadura) OR TS=(Tramagetic) OR TS=(Tramagit) OR TS=(Tramake) OR TS=(Tramal) OR TS=(Tramex) OR TS=(Adolonta) OR TS=(Contramal) OR TS=(Amadol)) #64 Triamcinolone (TS=(Triamcinolone) OR TS=(Volon) OR TS=(Aristocort)) 58 #65 Trolamine salicylate (TS=(Trolamine Salicylate) OR TS=(Triethanolamine Salicylate) OR 6 TS=(Myoflex)) #66 Valdecoxib (TS=(Valdecoxib) OR TS=(Bextra)) 13 #67 Vitamin D (TS=(Vitamin D)) 87 #68 Vitamin E (TS=(Vitamin E)) 21 #69 Zoledronic acid (TS=(Zoledronic Acid) OR TS=(Zoledronate) OR TS=(Zometa)) 11 #70 Final query #1 AND #2 AND (#3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR 974 Limit to Clinical Trial #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69) 492 493

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 494 eTable 1E - Final search strategy for Cochrane Central Register of Controlled Trials Topic or #ID Query Records intervention #1 Disease and study MeSH descriptor: [Osteoarthritis, Knee] explode all trees 3200 #2 design MeSH descriptor: [Osteoarthritis] explode all trees 5946 #3 MeSH descriptor: [Knee] explode all trees 717 #4 #2 and #3 96 #5 osteoarthritis:ti,ab,kw (Word variations have been searched) 11543 #6 knee:ti,ab,kw (Word variations have been searched) 19736 #7 #5 and #6 7634 #8 knee osteoarthritis:ti,ab,kw (Word variations have been searched) 7687 #9 #1 or #4 or #7 or #8 7687 #10 MeSH descriptor: [Randomized Controlled Trial] explode all trees 137 #11 MeSH descriptor: [Random Allocation] explode all trees 20619 #12 randomised controlled trial:ti,ab,kw (Word variations have been 481912 searched) #13 random allocation:ti,ab,kw (Word variations have been searched) 24970 #14 #10 or #11 or #12 or #13 498143 #15 #9 and #14 4504 #16 Aceclofenac aceclofenac:ti,ab,kw or "Falcol":ti,ab,kw or "Clanza CR":ti,ab,kw or 143 "Preservex":ti,ab,kw or "Biofenac":ti,ab,kw or "Sanein":ti,ab,kw or "Beofenac":ti,ab,kw or "Aital":ti,ab,kw or "Airtal":ti,ab,kw or "Bristaflam":ti,ab,kw or "Gerbin":ti,ab,kw #17 #15 and #16 9 #18 Acetaminophen Acetaminophen:ti,ab,kw or "Hydroxyacetanilide":ti,ab,kw or 8430 "APAP":ti,ab,kw or "Acetamidophenol":ti,ab,kw or "Paracetamol":ti,ab,kw or "Acephen":ti,ab,kw or "Acetaco":ti,ab,kw or "Tylenol":ti,ab,kw or "Anacin-3":ti,ab,kw or "Anacin 3":ti,ab,kw or "Anacin3":ti,ab,kw or "Datril":ti,ab,kw or "Panadol":ti,ab,kw or "Acamol":ti,ab,kw or "Algotropyl":ti,ab,kw #19 MeSH descriptor: [Acetaminophen] explode all trees 2749 #20 #18 or #19 8430 #21 #15 and #20 279 #22 Androstenedione MeSH descriptor: [Androstenedione] explode all trees 237 #23 Androstenedione:ti,ab,kw or "Androstene":ti,ab,kw 648 #24 #22 or #23 648 #25 #15 and #24 0 #26 ASA MeSH descriptor: [Aspirin] explode all trees 5268 #27 Aspirin:ti,ab,kw or "Acetylsalicylic Acid":ti,ab,kw or "Acylpyrin":ti,ab,kw 13782 or "Aloxiprimum":ti,ab,kw or "Colfarit":ti,ab,kw or "Dispril":ti,ab,kw or "Easprin":ti,ab,kw or "Ecotrin":ti,ab,kw or "Endosprin":ti,ab,kw or "Magnecyl":ti,ab,kw or "Micristin":ti,ab,kw or "Polopirin":ti,ab,kw or "Polopiryna":ti,ab,kw or "Solprin":ti,ab,kw or "Solupsan":ti,ab,kw or "Zorprin":ti,ab,kw or "Acetysal":ti,ab,kw #28 #26 or #27 13782 #29 #15 and #28 38 #30 Benoxaprofen Benoxaprofen:ti,ab,kw or "Oraflex":ti,ab,kw 38 #31 #15 and #30 1 #32 Betamethasone MeSH descriptor: [Betamethasone] explode all trees 1340 #33 Betamethasone:ti,ab,kw or "Flubenisolone":ti,ab,kw or 2089 "Betadexamethasone":ti,ab,kw or "Celestona":ti,ab,kw or "Cellestoderm":ti,ab,kw or "Celeston":ti,ab,kw or "Celestone":ti,ab,kw

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention #34 #32 or #33 2320 #35 #15 and #34 12 #36 Calcitonin MeSH descriptor: [Calcitonin] explode all trees 612 #37 Calcitonin:ti,ab,kw or "Calcitrin":ti,ab,kw or "Thyrocalcitonin":ti,ab,kw or 1462 "Ciba 47175-BA":ti,ab,kw or "Ciba 47175 BA":ti,ab,kw or "Ciba 47175BA":ti,ab,kw #38 #36 or #37 1462 #39 #15 and #38 8 #40 Capsaicin MeSH descriptor: [Capsaicin] explode all trees 544 #41 Capsaicin:ti,ab,kw or "Capsaicine":ti,ab,kw or "Axsain":ti,ab,kw or 1031 "Zacin":ti,ab,kw or "Capsidol":ti,ab,kw or "Zostrix":ti,ab,kw or "Capzasin":ti,ab,kw or "Gelcen":ti,ab,kw or "Katrum":ti,ab,kw or "Capsicum Farmaya":ti,ab,kw or "Capsin":ti,ab,kw #42 #40 or #41 1031 #43 #15 and #42 15 #44 Celecoxib MeSH descriptor: [Celecoxib] explode all trees 807 #45 Celecoxib:ti,ab,kw or "Celebrex":ti,ab,kw 1662 #46 #44 or #45 1662 #47 #15 and #46 98 #48 Chondroitin MeSH descriptor: [Chondroitin Sulfates] explode all trees 218 #49 Chondroitin Sulfate:ti,ab,kw or "Chondroitin":ti,ab,kw or 501 "Chonsurid":ti,ab,kw or "Translagen":ti,ab,kw or "Blutal":ti,ab,kw #50 #48 or #49 218 #51 #15 and #50 83 #52 Cindunistat Cindunistat:ti,ab,kw 2 #53 #15 and #52 1 #54 Cortivazol Cortivazol:ti,ab,kw 12 #55 #15 and #54 2 #56 Dexamethasone MeSH descriptor: [Dexamethasone] explode all trees 3746 #57 Dexamethasone:ti,ab,kw or "Methylfluorprednisolone":ti,ab,kw or 8781 "Hexadecadrol":ti,ab,kw or "Decameth":ti,ab,kw or "Decaspray":ti,ab,kw or "Dexasone":ti,ab,kw or "Dexpak":ti,ab,kw or "Maxidex":ti,ab,kw or "Millicorten":ti,ab,kw or "Oradexon":ti,ab,kw or "Decaject":ti,ab,kw or "Hexadrol":ti,ab,kw #58 #56 or #57 8799 #59 #15 and #58 11 #60 Diacerein Diacerein:ti,ab,kw or "Diacerhein":ti,ab,kw or "Diacetylrhein":ti,ab,kw or 84 "Diacetyl-rhein":ti,ab,kw or "Zondar":ti,ab,kw #61 #15 and #60 21 #62 Diclofenac MeSH descriptor: [Diclofenac] explode all trees 1766 #63 Diclofenac:ti,ab,kw or "Diclophenac":ti,ab,kw or "Dicrofenac":ti,ab,kw 4427 or "Dichlofenal":ti,ab,kw or "Diclonate P":ti,ab,kw or "Feloran":ti,ab,kw or "Voltarol":ti,ab,kw or "Novapirina":ti,ab,kw or "Orthofen":ti,ab,kw or "Ortofen":ti,ab,kw or "Orthophen":ti,ab,kw or "Voltaren":ti,ab,kw #64 #62 or #63 4427 #65 #15 and #64 172 #66 Diflunisal MeSH descriptor: [Diflunisal] explode all trees 99 #67 Diflunisal:ti,ab,kw or "Dolobid":ti,ab,kw or "Dolocid":ti,ab,kw or 250 "Dolobis":ti,ab,kw or "NuDifunisal":ti,ab,kw or "NovoDiflunisal":ti,ab,kw or "ApoDiflunisal":ti,ab,kw

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention #68 #66 or #67 250 #69 #15 and #68 8 #70 Doxycycline MeSH descriptor: [Doxycycline] explode all trees 960 #71 Doxycycline:ti,ab,kw or "Alpha-6-Deoxyoxytetracycline":ti,ab,kw or 1707 "Alpha 6 Deoxyoxytetracycline":ti,ab,kw or "Oracea":ti,ab,kw or "Periostat":ti,ab,kw or "Vibra-Tabs":ti,ab,kw or "Vibra Tabs":ti,ab,kw or "VibraTabs":ti,ab,kw or "Vibramycin":ti,ab,kw or "Vibravenos":ti,ab,kw or "Atridox":ti,ab,kw or "Doryx":ti,ab,kw or "Hydramycin":ti,ab,kw #72 #70 or #71 1707 #73 #15 and #72 9 #74 Duloxetine MeSH descriptor: [Duloxetine Hydrochloride] explode all trees 408 #75 Duloxetine:ti,ab,kw or "Propanamide":ti,ab,kw or "Cymbalta":ti,ab,kw 991 #76 #74 or #75 991 #77 #15 and #76 21 #78 Eltenac Eltenac:ti,ab,kw or "Telzenac":ti,ab,kw 2 #79 #15 and #78 0 #80 Etodolac MeSH descriptor: [Etodolac] explode all trees 105 #81 Etodolac:ti,ab,kw or "Etodolic Acid":ti,ab,kw or "Ultradol":ti,ab,kw or 247 "Lodine":ti,ab,kw or "Ramodar":ti,ab,kw #82 #80 or #81 247 #83 #15 and #82 13 #84 Etoricoxib Etoricoxib:ti,ab,kw or "Arcoxia":ti,ab,kw 338 #85 #15 and #84 12 #86 Fentanyl MeSH descriptor: [Fentanyl] explode all trees 5025 #87 Fentanyl:ti,ab,kw or "Phentanyl":ti,ab,kw or "Fentanest":ti,ab,kw or 11852 "Sublimaze":ti,ab,kw or "Duragesic":ti,ab,kw or "Durogesic":ti,ab,kw or "Fentora":ti,ab,kw #88 #86 or #87 12940 #89 #15 and #88 20 #90 Flurbiprofen MeSH descriptor: [Flurbiprofen] explode all trees 417 #91 Flurbiprofen:ti,ab,kw or "Flubiprofen":ti,ab,kw or "Fluriproben":ti,ab,kw 809 or "Cebutid":ti,ab,kw or "Dobrofen":ti,ab,kw or "Flugalin":ti,ab,kw or "Froben":ti,ab,kw or "Neo Artrol":ti,ab,kw or "Ocufen":ti,ab,kw or "Ocuflur":ti,ab,kw or "Strefen":ti,ab,kw or "Ansaid":ti,ab,kw #92 #90 or #91 809 #93 #15 and #92 16 #94 Corticosteroids MeSH descriptor: [Adrenal Cortex Hormones] explode all trees 13406 #95 Adrenal Cortex Hormones:ti,ab,kw or "Corticosteroid":ti,ab,kw or 17086 "Corticosteroids":ti,ab,kw or "Corticoid":ti,ab,kw or "Corticoids":ti,ab,kw #96 #94 or #95 26391 #97 #15 and #96 115 #98 Glucosamine MeSH descriptor: [Glucosamine] explode all trees 220 #99 Glucosamine:ti,ab,kw or "Hespercorbin":ti,ab,kw or "Dona":ti,ab,kw or 556 "Xicil":ti,ab,kw #100 #98 or #99 572 #101 #15 and #100 132 #102 Hyaluronic acid MeSH descriptor: [Hyaluronic Acid] explode all trees 1312 #103 Hyaluronic Acid:ti,ab,kw or "Amo Vitrax":ti,ab,kw or "Biolon":ti,ab,kw or 8067 "Etamucine":ti,ab,kw or "Hyaluronan":ti,ab,kw or "Hyvisc":ti,ab,kw or

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention "Luronit":ti,ab,kw or "Hyaluronate":ti,ab,kw or "Amvisc":ti,ab,kw or "Healon":ti,ab,kw or "Synvisc":ti,ab,kw or "Orthovisc":ti,ab,kw or "Hyalectin":ti,ab,kw or "Hyalgan":ti,ab,kw or "Vitrax":ti,ab,kw or "Ostenil":ti,ab,kw or "Hylan":ti,ab,kw or "Suplasyn":ti,ab,kw or "Arthrum":ti,ab,kw or "Go-on":ti,ab,kw or "Hyalart":ti,ab,kw or "Nuflexxa":ti,ab,kw or "Replasyn":ti,ab,kw or "Durolane":ti,ab,kw or "Supartz":ti,ab,kw #104 #102 or #103 8067 #105 #15 and #104 278 #106 Hydrocortisone MeSH descriptor: [Hydrocortisone] explode all trees 5584 #107 Hydrocortisone:ti,ab,kw or "Cortisol":ti,ab,kw or "Epicortisol":ti,ab,kw or 11241 "Cortifair":ti,ab,kw or "Cortril":ti,ab,kw #108 #106 or #107 11307 #109 #15 and #108 10 #110 Ibuprofen MeSH descriptor: [Ibuprofen] explode all trees 1701 #111 Ibuprofen:ti,ab,kw or "Ibumetin":ti,ab,kw or "IP-82":ti,ab,kw or "IP 3794 82":ti,ab,kw or "IP82":ti,ab,kw or "Motrin":ti,ab,kw or "Nuprin":ti,ab,kw or "Rufen":ti,ab,kw or "Salprofen":ti,ab,kw or "Trauma-Dolgit Gel":ti,ab,kw or "Trauma Dolgit Gel":ti,ab,kw or "TraumaDolgit Gel":ti,ab,kw or "Brufen":ti,ab,kw #112 #110 or #111 3794 #113 #15 and #112 87 #114 Indomethacin MeSH descriptor: [Indomethacin] explode all trees 2442 #115 Indomethacin:ti,ab,kw or "Indometacin":ti,ab,kw or "Amuno":ti,ab,kw or 2951 "Indocid":ti,ab,kw or "Metindol":ti,ab,kw or "Indomet 140":ti,ab,kw or "Osmosin":ti,ab,kw or "Indocin":ti,ab,kw #116 #114 or #115 3880 #117 #15 and #116 31 #118 Ketoprofen MeSH descriptor: [Ketoprofen] explode all trees 520 #119 Ketoprofen:ti,ab,kw or "Benzoylhydratropic Acid":ti,ab,kw or 1105 "Profenid":ti,ab,kw or "Alrheumum":ti,ab,kw or "Orudis":ti,ab,kw or "Alrheumat":ti,ab,kw #120 #118 or #119 1105 #121 #15 and #120 20 #122 Ketorolac MeSH descriptor: [Ketorolac] explode all trees 733 #123 Ketorolac:ti,ab,kw or "Acular":ti,ab,kw or "Toradol":ti,ab,kw 2269 #124 #122 or #123 2269 #125 #15 and #124 16 #126 Licofelone Licofelone:ti,ab,kw 6 #127 #15 and #126 1 #128 Lornoxicam Lornoxicam:ti,ab,kw or "Chlortenoxicam":ti,ab,kw or "Xefocam":ti,ab,kw 267 #129 #15 and #128 8 #130 Lumiracoxib Lumiracoxib:ti,ab,kw or "Prexige":ti,ab,kw 81 #131 #15 and #130 7 #132 MMP Inhibitors MeSH descriptor: [Matrix Metalloproteinase Inhibitors] explode all trees 74 #133 Matrix Metalloproteinase Inhibitors:ti,ab,kw or "Matrix 299 Metalloproteinase Inhibitor":ti,ab,kw or "MMP Inhibitors":ti,ab,kw or "MMP Inhibitor":ti,ab,kw or "Stromelysin Inhibitors":ti,ab,kw or "Stromelysin Inhibitor":ti,ab,kw or "Gelatinase Inhibitors":ti,ab,kw or "Gelatinase Inhibitor":ti,ab,kw or "Collagenase Inhibitors":ti,ab,kw or

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention "Collagenase Inhibitor":ti,ab,kw #134 #132 or #133 299 #135 #15 and #134 3 #136 Meloxicam Meloxicam:ti,ab,kw or "Reumoxicam":ti,ab,kw or "Miloxicam":ti,ab,kw 481 or "Movalis":ti,ab,kw or "Uticox":ti,ab,kw or "Mobic":ti,ab,kw or "Mobicox":ti,ab,kw or "Mobec":ti,ab,kw or "Masflex":ti,ab,kw or "Movicox":ti,ab,kw or "Parocin":ti,ab,kw #137 #15 and #136 18 #138 Metamizole MeSH descriptor: [Dipyrone] explode all trees 219 #139 Metamizole:ti,ab,kw or "Dipyrone":ti,ab,kw or "Noramidopyrine 753 Methanesulfonate Sodium":ti,ab,kw or "Metamizol":ti,ab,kw or "Methamizole":ti,ab,kw or "Dipyronium":ti,ab,kw or "Methampyrone":ti,ab,kw or "Novaminsulfone":ti,ab,kw or "Sulpyrin":ti,ab,kw or "Sulpyrine":ti,ab,kw or "Optalgin":ti,ab,kw or "Novalgin":ti,ab,kw or "Analgin":ti,ab,kw or "Narone":ti,ab,kw or "Biopyrin":ti,ab,kw or "Noramidopyrine Methanesulfonate":ti,ab,kw or "Normelubrine":ti,ab,kw or "Novalgetol":ti,ab,kw or "Pyralgin":ti,ab,kw or "Algopyrin":ti,ab,kw #140 #138 or #139 753 #141 #15 and #140 4 #142 Methylprednisolone MeSH descriptor: [Methylprednisolone] explode all trees 2322 #143 Methylprednisolone:ti,ab,kw or "Metipred":ti,ab,kw or 4462 "Urbason":ti,ab,kw or "Medrol":ti,ab,kw or "UrbasonSoluble":ti,ab,kw or "SoluMedrol":ti,ab,kw or "A-MethaPred":ti,ab,kw #144 #142 or #143 4462 #145 #15 and #144 41 #146 Methylsulfonylmethane Dimethyl Sulfone:ti,ab,kw or "Methyl Sulfonmethane":ti,ab,kw or 41 "Methylsulfonylmethane":ti,ab,kw or "Methyl Sulfone":ti,ab,kw #147 #15 and #146 9 #148 Nabumetone Nabumetone:ti,ab,kw or "Nabumeton":ti,ab,kw or "Arthraxan":ti,ab,kw 171 or "Listran":ti,ab,kw or "Relafen":ti,ab,kw or "Relif":ti,ab,kw or "Relifex":ti,ab,kw or "Mebutan":ti,ab,kw or "Nabucox":ti,ab,kw #149 #15 and #148 18 #150 Naproxcinod Naproxcinod:ti,ab,kw or "NO-naproxen":ti,ab,kw or "Nitric Oxide 40 Naproxen":ti,ab,kw or "NicOx":ti,ab,kw #151 #15 and #150 0 #152 Naproxen MeSH descriptor: [Naproxen] explode all trees 1066 #153 Naproxen:ti,ab,kw or "Methoxypropiocin":ti,ab,kw or "MNPA":ti,ab,kw 2058 or "Anaprox":ti,ab,kw or "Naprosin":ti,ab,kw or "Naprosyn":ti,ab,kw or "Proxen":ti,ab,kw or "Synflex":ti,ab,kw or "Aleve":ti,ab,kw #154 #152 or #153 2058 #155 #15 and #154 78 #156 Nimesulide Nimesulide:ti,ab,kw or "Aulin":ti,ab,kw or "Eskaflam":ti,ab,kw or 344 "lizepat":ti,ab,kw or "Mesulid":ti,ab,kw or "Nexen":ti,ab,kw or "Nimesil":ti,ab,kw or "Redaflam":ti,ab,kw or "Antifloxil":ti,ab,kw or "Guaxan":ti,ab,kw #157 #15 and #156 12 #158 Opioids MeSH descriptor: [Analgesics, Opioid] explode all trees 6547 #159 Opioid Analgesics:ti,ab,kw or "Opioid Analgesic":ti,ab,kw or 17367 "Opioids":ti,ab,kw or "Opioid":ti,ab,kw #160 #158 or #159 17367

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention #161 #15 and #160 79 #162 Oxaprozin Oxaprozin:ti,ab,kw or "Danoprox":ti,ab,kw or "Dayrun":ti,ab,kw or 57 "Daypro":ti,ab,kw #163 #15 and #162 7 #164 Parecoxib Parecoxib:ti,ab,kw or "Dynastat":ti,ab,kw 376 #165 #15 and #164 1 #166 Pennsaid Pennsaid:ti,ab,kw 6 #167 #15 and #166 3 #168 Piroxicam MeSH descriptor: [Piroxicam] explode all trees 632 #169 Piroxicam:ti,ab,kw or "Feldene":ti,ab,kw 1141 #170 #168 or #169 1141 #171 #15 and #170 45 #172 Prednisolone MeSH descriptor: [Prednisolone] explode all trees 4374 #173 Prednisolone:ti,ab,kw or "Predate":ti,ab,kw or "Predonine":ti,ab,kw or 5798 "Di-Adreson-F":ti,ab,kw or "DiAdreson F":ti,ab,kw or "DiAdresonF":ti,ab,kw #174 #172 or #173 7460 #175 #15 and #174 17 #176 Risedronate MeSH descriptor: [Risedronate Sodium] explode all trees 304 #177 Risedronate:ti,ab,kw or "Risedronic Acid":ti,ab,kw or "Actonel":ti,ab,kw 559 or "Atelvia":ti,ab,kw #178 #176 or #177 559 #179 #15 and #178 5 #180 Rofecoxib Rofecoxib:ti,ab,kw or "Vioxx":ti,ab,kw 488 #181 #15 and #180 23 #182 SAME MeSH descriptor: [S-Adenosylmethionine] explode all trees 123 #183 S-Adenosylmethionine:ti,ab,kw or "SAME":ti,ab,kw or "SAM-e":ti,ab,kw 75575 or "AdoMet":ti,ab,kw or "S-Adenosyl-L-Methionine":ti,ab,kw or "S Adenosyl L Methionine":ti,ab,kw or "Ademetionine":ti,ab,kw or "S Amet":ti,ab,kw or "Samyr":ti,ab,kw or "Gumbaral":ti,ab,kw #184 #182 or #183 75575 #185 #15 and #184 294 #186 Sprifermin Fibroblast Growth Factor 18:ti,ab,kw or "Sprifermin":ti,ab,kw 222 #187 #15 and #186 4 #188 Steroids MeSH descriptor: [Steroids] explode all trees 52468 #189 Steroid:ti,ab,kw or "Steroids":ti,ab,kw 16551 #190 #188 or #189 63143 #191 #15 and #190 87 #192 Strontium ranelate Strontium Ranelate:ti,ab,kw or "Protelos":ti,ab,kw 147 #193 #15 and #192 11 #194 Sulindac MeSH descriptor: [Sulindac] explode all trees 160 #195 Sulindac:ti,ab,kw or "Apo-Sulin":ti,ab,kw or "Apo Sulin":ti,ab,kw or 362 "Arthrobid":ti,ab,kw or "Clinoril":ti,ab,kw or "Arthrocine":ti,ab,kw or "Klinoril":ti,ab,kw or "Sulindal":ti,ab,kw or "Chibret":ti,ab,kw or "Kenalin":ti,ab,kw or "Novo-Sundac":ti,ab,kw or "Novo Sundac":ti,ab,kw or "Aclin":ti,ab,kw or "Copal":ti,ab,kw #196 #194 or #195 362 #197 #15 and #196 8

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention #198 Tenidap Tenidap:ti,ab,kw 30 #199 #15 and #198 0 #200 Tenoxicam Tenoxicam:ti,ab,kw or "Reutenox":ti,ab,kw or "Artriunic":ti,ab,kw or 392 "Mobiflex":ti,ab,kw or "Tilcotil":ti,ab,kw #201 #15 and #200 9 #202 Tiaprofenic acid Tiaprofenic Acid:ti,ab,kw or "Flanid":ti,ab,kw or "Nu- 130 Tiaprofenic":ti,ab,kw or "PMS-Tiaprofenic":ti,ab,kw or "Surgam":ti,ab,kw or "Apo-Tiaprofenic":ti,ab,kw or "Novo- Tiaprofenic":ti,ab,kw #203 #15 and #202 6 #204 Tolmetin-Na MeSH descriptor: [Tolmetin] explode all trees 363 #205 Tolmetin:ti,ab,kw or "Tolectin":ti,ab,kw 435 #206 #204 or #205 435 #207 #15 and #206 0 #208 Tramadol MeSH descriptor: [Tramadol] explode all trees 997 #209 Tramadol:ti,ab,kw or "Tramundin":ti,ab,kw or "Biodalgic":ti,ab,kw or 2958 "Jutadol":ti,ab,kw or "Nobligan":ti,ab,kw or "Prontofort":ti,ab,kw or "Zytram":ti,ab,kw or "Takadol":ti,ab,kw or "Theradol":ti,ab,kw or "Tiral":ti,ab,kw or "Topalgic":ti,ab,kw or "Tradol":ti,ab,kw or "TradolPuren":ti,ab,kw or "Tradonal":ti,ab,kw or "Tralgiol":ti,ab,kw or "Trama":ti,ab,kw or "TramaDorsch":ti,ab,kw or "Biokanol":ti,ab,kw or "Tramabeta":ti,ab,kw or "Tramadin":ti,ab,kw or "Tramadolratiopharm":ti,ab,kw or "Tramadoc":ti,ab,kw or "Ranitidin 1A Pharma":ti,ab,kw or "Trasedal":ti,ab,kw or "Ultram":ti,ab,kw or "Xymel 50":ti,ab,kw or "Zamudol":ti,ab,kw or "Zydol":ti,ab,kw or "TramadolDolgit":ti,ab,kw or "TramadolHameln":ti,ab,kw or "Tramadolor":ti,ab,kw or "Tramadura":ti,ab,kw or "Tramagetic":ti,ab,kw or "Tramagit":ti,ab,kw or "Tramake":ti,ab,kw or "Tramal":ti,ab,kw or "Tramex":ti,ab,kw or "Adolonta":ti,ab,kw or "Contramal":ti,ab,kw or "Amadol":ti,ab,kw #210 #208 or #209 2958 #211 #15 and #210 35 #212 Triamcinolone MeSH descriptor: [Triamcinolone] explode all trees 1189 #213 Triamcinolone:ti,ab,kw or "Volon":ti,ab,kw or "Aristocort":ti,ab,kw 2364 #214 #212 or #213 2364 #215 #15 and #214 34 #216 Trolamine salicylate Trolamine Salicylate:ti,ab,kw or "Triethanolamine Salicylate":ti,ab,kw 16 or "Myoflex":ti,ab,kw #217 #15 and #216 2 #218 Valdecoxib Valdecoxib:ti,ab,kw or "Bextra":ti,ab,kw 149 #219 #15 and #218 3 #220 Vitamin D MeSH descriptor: [Vitamin D] explode all trees 4274 #221 Vitamin D:ti,ab,kw 9803 #222 #220 or #221 10641 #223 #15 and #222 43 #224 Vitamin E MeSH descriptor: [Vitamin E] explode all trees 2336 #225 Vitamin E:ti,ab,kw 4994 #226 #224 or #225 5298 #227 #15 and #226 9 #228 Zoledronic acid Zoledronic Acid:ti,ab,kw or "Zoledronate":ti,ab,kw or "Zometa":ti,ab,kw 1204

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 Topic or #ID Query Records intervention #229 #15 and #228 2 #230 All treatments #16 or #20 or #24 or #28 or #30 or #34 or #38 or #42 or #46 or #50 or 229845 #52 or #54 or #58 or #60 or #64 or #68 or #72 or #76 or #78 or #82 or #84 or #88 or #92 or #96 or #100 or #104 or #108 or #112 or #116 or #120 or #124 or #126 or #128 or #130 or #134 or #136 or #140 or #144 or #146 or #148 or #150 or #154 or #156 or #160 or #162 or #164 or #166 or #170 or #174 or #178 or #180 or #184 or #186 or #190 or #192 or #196 or #198 or #200 or #202 or #206 or #210 or #214 or #216 or #218 or #222 or #226 or #228 #231 Final query #15 and #230 1512 495 496

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 497 eTable 2 - Hierarchy of tools for patient-reported outcomes assessment Pain outcome 1) WOMAC - Pain subscale (Likert/VAS100 mm) 2) Pain during activity (VAS) 3) Pain during walking (VAS) 4) Global knee pain (VAS) 5) Pain at rest (VAS) 6) SF-36 (bodily pain (BP) subscale) 7) HAQ (pain subscale), Lequesne algofunctional index (pain subscale), AIMS (pain subscale), Knee- specific Pain Scale (KSPS), McGill Pain Questionnaire (pain intensity), ASES (pain subscale), SES (Schmerzempfindungsskala) 8) Pain at night (VAS), pain during activity (NRS), pain on walking (NRS), number of painful days (days) Function outcome 1) WOMAC subscale function (Likert/VAS 100 mm) 2) SF-36 (subscale physical function (PF)) 3) Physical Composite Score (PCS) based on SF-36, SF-12 or SF-8 4) HAQ (disability subscale), PDI (pain disability index), ASES (disability subscale) 498 AIMS Arthritis Impact Measurement Scale; ASES Arthritis Self-Efficacy Scale; BP bodily pain; HAQ Health Assessment Questionnaire; 499 NRS Numerical Rating Scale; PCS Physical Composite Scale; PDI Pain Disability Index; PF physical function; SES 500 Schmerzempfindungsskala; SF-8 Short Form 8; SF-12 Short Form 12; SF-36 Short Form 36; VAS Visual Analogue Scale; WOMAC 501 Western Ontario and McMaster Universities Osteoarthritis Index. 502 503

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 628 eTable 3 - Pain (primary outcome): league table – when trials at high risk of bias were excluded 629 Treatments in diagonal cells are reported in order of relative ranking for efficacy. Direct comparisons are reported in light grey cells, while significant estimates are presented in bold. 630 Comparisons between treatments read from left to right: a network estimate less than 0 indicates that treatment reported in column is more effective than corresponding treatment reported in 631 row. Point estimates refer to the posterior mean. ACT Acetaminophen; CS Chondroitin Sulfate; BMS Betamethasone; HA Hyaluronic Acid; MTP Methylprednisolone; TRM Triamcinolone. 632

633 HA+TRM

-0.18 Glucosamine (-0.83, 0.52) Sulfate

-0.31 -0.13 Celecoxib (-0.95, 0.39) (-0.39, 0.13)

-0.34 -0.17 -0.04 Vitamin D (-1.00, 0.33) (-0.43, 0.09) (-0.27, 0.20)

-0.36 -0.19 -0.06 -0.02 (-1.02, 0.32) (-0.42, 0.05) (-0.26, 0.15) (-0.22, 0.19) Calcitonin

-0.36 -0.18 -0.05 -0.01 0.00 Glucosamines + (-1.01, 0.32) (-0.43, 0.07) (-0.24, 0.14) (-0.24, 0.21) (-0.19, 0.20) CS

-0.39 -0.21 -0.08 -0.04 -0.02 -0.03 Etoricoxib (-1.07, 0.33) (-0.53, 0.12) (-0.29, 0.13) (-0.35, 0.27) (-0.31, 0.26) (-0.3, 0.25)

-0.38 -0.20 -0.07 -0.03 -0.01 -0.02 0.01 Strontium (-1.01, 0.30) (-0.42, 0.02) (-0.27, 0.13) (-0.23, 0.16) (-0.17, 0.14) (-0.21, 0.17) (-0.27, 0.28) Ranelate

-0.4 -0.22 -0.09 -0.05 -0.03 -0.04 -0.01 -0.02 Glucosamines (-1.05, 0.29) (-0.47, 0.04) (-0.28, 0.10) (-0.28, 0.18) (-0.23, 0.17) (-0.21, 0.14) (-0.28, 0.26) (-0.2, 0.17)

-0.41 -0.23 -0.10 -0.06 -0.04 -0.05 -0.02 -0.03 -0.01 Naproxen (-1.11, 0.33) (-0.59, 0.14) (-0.37, 0.17) (-0.41, 0.29) (-0.37, 0.29) (-0.37, 0.28) (-0.19, 0.15) (-0.35, 0.30) (-0.33, 0.31)

-0.42 -0.24 -0.11 -0.07 -0.06 -0.06 -0.03 -0.04 -0.02 -0.01 Chondroitin (-1.06, 0.25) (-0.47, -0.01) (-0.27, 0.05) (-0.27, 0.13) (-0.22, 0.11) (-0.22, 0.10) (-0.29, 0.22) (-0.19, 0.11) (-0.18, 0.13) (-0.32, 0.29) Sulfate (CS)

-0.41 -0.24 -0.11 -0.07 -0.05 -0.06 -0.03 -0.04 -0.02 -0.01 0.00 Hyaluronic Acid (-1.04, 0.23) (-0.47, -0.00) (-0.32, 0.10) (-0.27, 0.14) (-0.23, 0.12) (-0.26, 0.15) (-0.32, 0.26) (-0.2, 0.12) (-0.22, 0.18) (-0.34, 0.33) (-0.16, 0.17) (HA)

-0.42 -0.24 -0.11 -0.07 -0.06 -0.06 -0.03 -0.04 -0.02 -0.01 -0.00 -0.01 Nimesulide (-1.15, 0.34) (-0.66, 0.18) (-0.45, 0.23) (-0.48, 0.33) (-0.45, 0.34) (-0.44, 0.33) (-0.31, 0.24) (-0.42, 0.35) (-0.41, 0.36) (-0.23, 0.20) (-0.37, 0.37) (-0.40, 0.39)

-0.43 -0.25 -0.12 -0.08 -0.06 -0.06 -0.04 -0.05 -0.03 -0.02 -0.01 -0.01 0.00 Cindunistat (-1.07, 0.25) (-0.47, -0.02) (-0.31, 0.08) (-0.27, 0.12) (-0.22, 0.10) (-0.25, 0.12) (-0.31, 0.24) (-0.19, 0.1) (-0.22, 0.16) (-0.34, 0.31) (-0.16, 0.14) (-0.17, 0.15) (-0.39, 0.38)

-0.43 -0.25 -0.13 -0.09 -0.07 -0.07 -0.05 -0.05 -0.04 -0.03 -0.01 -0.02 -0.01 -0.01 Risedronate (-1.07, 0.24) (-0.46, -0.05) (-0.31, 0.06) (-0.26, 0.09) (-0.21, 0.07) (-0.24, 0.10) (-0.31, 0.22) (-0.18, 0.07) (-0.21, 0.13) (-0.34, 0.29) (-0.14, 0.12) (-0.16, 0.12) (-0.39, 0.36) (-0.13, 0.11)

-0.43 -0.25 -0.13 -0.09 -0.07 -0.08 -0.05 -0.06 -0.04 -0.03 -0.02 -0.02 -0.01 -0.01 0.00 Diacerein (-1.10, 0.25) (-0.60, 0.07) (-0.44, 0.18) (-0.40, 0.23) (-0.36, 0.22) (-0.38, 0.23) (-0.42, 0.32) (-0.34, 0.23) (-0.35, 0.27) (-0.44, 0.38) (-0.30, 0.27) (-0.28, 0.24) (-0.49, 0.44) (-0.29, 0.27) (-0.27, 0.27)

-0.45 -0.27 -0.14 -0.1 -0.09 -0.09 -0.07 -0.07 -0.06 -0.04 -0.03 -0.04 -0.03 -0.03 -0.02 -0.02 Licofelone (-1.19, 0.33) (-0.71, 0.16) (-0.50, 0.21) (-0.53, 0.32) (-0.50, 0.32) (-0.49, 0.31) (-0.36, 0.22) (-0.47, 0.33) (-0.46, 0.34) (-0.28, 0.19) (-0.42, 0.35) (-0.45, 0.38) (-0.35, 0.29) (-0.43, 0.37) (-0.41, 0.38) (-0.48, 0.46)

-0.46 -0.29 -0.16 -0.12 -0.11 -0.11 -0.09 -0.09 -0.07 -0.06 -0.05 -0.05 -0.05 -0.04 -0.04 -0.03 -0.02 Placebo (-1.12, 0.20) (-0.49, -0.10) (-0.33, 0.01) (-0.29, 0.04) (-0.23, 0.01) (-0.27, 0.05) (-0.34, 0.18) (-0.19, 0.01) (-0.23, 0.08) (-0.37, 0.25) (-0.16, 0.06) (-0.18, 0.07) (-0.43, 0.33) (-0.14, 0.06) (-0.10, 0.03) (-0.31, 0.24) (-0.41, 0.38)

-0.48 -0.30 -0.17 -0.13 -0.12 -0.12 -0.09 -0.10 -0.08 -0.07 -0.06 -0.06 -0.06 -0.05 -0.05 -0.05 -0.03 -0.01 Diclofenac (-1.14, 0.22) (-0.59, -0.02) (-0.31, -0.03) (-0.40, 0.13) (-0.36, 0.13) (-0.36, 0.11) (-0.25, 0.06) (-0.34, 0.13) (-0.32, 0.15) (-0.30, 0.16) (-0.27, 0.15) (-0.31, 0.18) (-0.37, 0.25) (-0.29, 0.18) (-0.27, 0.18) (-0.38, 0.29) (-0.35, 0.30) (-0.21, 0.20)

-0.59 -0.41 -0.28 -0.24 -0.23 -0.23 -0.21 -0.21 -0.20 -0.18 -0.17 -0.18 -0.17 -0.17 -0.16 -0.16 -0.14 -0.12 -0.11 Rofecoxib (-1.26, 0.13) (-0.73, -0.10) (-0.48, -0.09) (-0.55, 0.05) (-0.50, 0.04) (-0.50, 0.03) (-0.40, -0.01) (-0.48, 0.05) (-0.46, 0.07) (-0.45, 0.08) (-0.42, 0.07) (-0.46, 0.10) (-0.51, 0.16) (-0.43, 0.10) (-0.41, 0.09) (-0.52, 0.20) (-0.49, 0.21) (-0.37, 0.13) (-0.24, 0.02)

-0.69 -0.51 -0.38 -0.34 -0.32 -0.32 -0.30 -0.31 -0.29 -0.28 -0.26 -0.27 -0.27 -0.26 -0.25 -0.25 -0.23 -0.22 -0.21 -0.10 Vitamin E (-1.42, 0.07) (-0.93, -0.09) (-0.78, 0.01) (-0.75, 0.06) (-0.71, 0.06) (-0.73, 0.07) (-0.74, 0.14) (-0.69, 0.07) (-0.69, 0.11) (-0.75, 0.20) (-0.65, 0.11) (-0.66, 0.11) (-0.78, 0.25) (-0.64, 0.11) (-0.62, 0.12) (-0.70, 0.20) (-0.77, 0.30) (-0.59, 0.15) (-0.62, 0.21) (-0.53, 0.34)

-0.73 -0.54 -0.42 -0.38 -0.36 -0.36 -0.34 -0.34 -0.33 -0.32 -0.31 -0.31 -0.30 -0.30 -0.29 -0.29 -0.28 -0.26 -0.24 -0.13 -0.03 Triamcinolone (-1.44, 0.03) (-0.94, -0.16) (-0.80, -0.04) (-0.75, -0.00) (-0.73, -0.00) (-0.74, 0.01) (-0.77, 0.09) (-0.70, 0.01) (-0.70, 0.05) (-0.78, 0.15) (-0.67, 0.06) (-0.67, 0.05) (-0.81, 0.20) (-0.65, 0.06) (-0.64, 0.06) (-0.72, 0.15) (-0.78, 0.25) (-0.60, 0.09) (-0.65, 0.16) (-0.56, 0.29) (-0.54, 0.47)

-0.99 -0.81 -0.68 -0.64 -0.62 -0.63 -0.60 -0.61 -0.59 -0.58 -0.57 -0.57 -0.57 -0.56 -0.55 -0.55 -0.54 -0.52 -0.51 -0.39 -0.30 -0.26 Sprifermin (-1.66, -0.28) (-1.14, -0.48) (-1.00, -0.37) (-0.95, -0.33) (-0.91, -0.34) (-0.93, -0.32) (-0.97, -0.24) (-0.89, -0.33) (-0.89, -0.28) (-0.99, -0.18) (-0.85, -0.28) (-0.87, -0.28) (-1.02, -0.11) (-0.85, -0.28) (-0.83, -0.28) (-0.93, -0.18) (-1.01, -0.07) (-0.77, -0.26) (-0.84, -0.17) (-0.76, -0.04) (-0.74, 0.15) (-0.68, 0.17)

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 634 635 eTable 4 - Pain (primary outcome): league table – All trials 636 Treatments in diagonal cells are reported in order of relative ranking for efficacy. Direct comparisons are reported in light grey cells, while significant estimates are presented in bold. 637 Comparisons between treatments read from left to right: a network estimate less than 0 indicates that treatment reported in column is more effective than corresponding treatment reported in 638 row. Point estimates refer to the posterior mean. ACT Acetaminophen; CS Chondroitin Sulfate; BMS Betamethasone; HA Hyaluronic Acid; MTP Methylprednisolone; TRM Triamcinolone.

HA + TRM

-0.09 HA + BMS (-0.89,0.73)

-0.20 -0.11 Glucosamine (-0.88,0.48) (-0.65,0.41) Sulfate

-0.31 -0.23 -0.11 Celecoxib (-0.99,0.37) (-0.74,0.28) (-0.37,0.15)

-0.37 -0.28 -0.17 -0.06 Glucosamines (-1.04,0.30) (-0.79,0.22) (-0.42,0.09) (-0.25,0.14) + CS

-0.37 -0.29 -0.17 -0.06 -0.01 Vitamin D (-1.04,0.31) (-0.80,0.23) (-0.43,0.09) (-0.30,0.18) (-0.24,0.22)

-0.39 -0.30 -0.19 -0.07 -0.02 -0.01 Calcitonin (-1.05,0.28) (-0.81,0.20) (-0.42,0.05) (-0.28,0.14) (-0.21,0.18) (-0.22,0.19)

-0.39 -0.30 -0.18 -0.07 -0.02 -0.01 0.00 Glucosamines (-1.05,0.28) (-0.81,0.20) (-0.43,0.07) (-0.26,0.12) (-0.18,0.15) (-0.23,0.21) (-0.19,0.19)

-0.39 -0.31 -0.19 -0.08 -0.02 -0.02 -0.01 -0.01 Etoricoxib (-1.11,0.31) (-0.86,0.24) (-0.51,0.13) (-0.28,0.12) (-0.30,0.25) (-0.32,0.28) (-0.29,0.27) (-0.28,0.26)

-0.40 -0.32 -0.20 -0.09 -0.03 -0.03 -0.02 -0.02 -0.01 Strontium (-1.06,0.26) (-0.81,0.17) (-0.42,0.02) (-0.29,0.11) (-0.22,0.15) (-0.22,0.17) (-0.17,0.14) (-0.2,0.16) (-0.28,0.26) Ranelate

-0.41 -0.33 -0.21 -0.10 -0.04 -0.04 -0.03 -0.03 -0.02 -0.01 Naproxen (-1.14,0.31) (-0.90,0.25) (-0.58,0.15) (-0.37,0.16) (-0.37,0.28) (-0.39,0.31) (-0.35,0.30) (-0.35,0.29) (-0.19,0.15) (-0.33,0.31)

-0.43 -0.34 -0.23 -0.12 -0.06 -0.06 -0.04 -0.04 -0.04 -0.03 -0.02 MTP (-1.16,0.30) (-0.92,0.24) (-0.65,0.19) (-0.53,0.30) (-0.46,0.35) (-0.46,0.36) (-0.44,0.35) (-0.45,0.36) (-0.48,0.41) (-0.41,0.36) (-0.49,0.46)

-0.42 -0.34 -0.22 -0.11 -0.05 -0.05 -0.04 -0.04 -0.03 -0.02 -0.01 0.01 Nimesulide (-1.18,0.32) (-0.94,0.27) (-0.64,0.19) (-0.45,0.23) (-0.44,0.33) (-0.46,0.36) (-0.43,0.35) (-0.42,0.34) (-0.30,0.24) (-0.4,0.36) (-0.22,0.20) (-0.52,0.52)

-0.43 -0.34 -0.23 -0.12 -0.06 -0.06 -0.04 -0.05 -0.04 -0.03 -0.02 0.00 -0.01 Chondroitin (-1.09,0.23) (-0.85,0.15) (-0.46,0.00) (-0.28,0.04) (-0.22,0.10) (-0.26,0.14) (-0.21,0.12) (-0.20,0.11) (-0.29,0.21) (-0.18,0.12) (-0.33,0.29) (-0.39,0.38) (-0.38,0.36) Sulfate

-0.43 -0.34 -0.23 -0.12 -0.06 -0.06 -0.04 -0.05 -0.04 -0.03 -0.02 0.00 -0.01 0.00 HA (-1.06,0.21) (-0.81,0.12) (-0.46,0.01) (-0.33,0.09) (-0.26,0.14) (-0.26,0.15) (-0.21,0.12) (-0.23,0.14) (-0.32,0.24) (-0.19,0.13) (-0.34,0.31) (-0.35,0.35) (-0.39,0.38) (-0.16,0.16)

-0.45 -0.36 -0.25 -0.14 -0.08 -0.08 -0.06 -0.06 -0.06 -0.05 -0.04 -0.02 -0.03 -0.02 -0.02 Tiaprofenic (-1.11,0.23) (-0.88,0.15) (-0.51,0.02) (-0.38,0.10) (-0.31,0.15) (-0.32,0.17) (-0.27,0.15) (-0.29,0.16) (-0.36,0.25) (-0.24,0.15) (-0.38,0.31) (-0.44,0.38) (-0.43,0.38) (-0.22,0.18) (-0.23,0.19) Acid

-0.45 -0.36 -0.25 -0.14 -0.08 -0.08 -0.06 -0.07 -0.06 -0.05 -0.04 -0.02 -0.03 -0.02 -0.02 0.00 Cindunistat (-1.1,0.21) (-0.86,0.13) (-0.47,-0.03) (-0.33,0.06) (-0.27,0.11) (-0.27,0.12) (-0.22,0.09) (-0.25,0.11) (-0.33,0.22) (-0.19,0.10) (-0.36,0.29) (-0.41,0.37) (-0.41,0.36) (-0.17,0.13) (-0.17,0.14) (-0.20,0.20)

-0.46 -0.37 -0.26 -0.15 -0.09 -0.09 -0.07 -0.07 -0.07 -0.06 -0.05 -0.03 -0.04 -0.03 -0.03 -0.01 -0.01 Diacerein (-1.15,0.23) (-0.91,0.17) (-0.58,0.07) (-0.46,0.17) (-0.39,0.22) (-0.40,0.23) (-0.36,0.22) (-0.37,0.23) (-0.44,0.30) (-0.33,0.23) (-0.45,0.36) (-0.46,0.41) (-0.49,0.42) (-0.31,0.26) (-0.29,0.23) (-0.32,0.30) (-0.29,0.28)

-0.46 -0.37 -0.26 -0.15 -0.09 -0.09 -0.07 -0.08 -0.07 -0.06 -0.05 -0.03 -0.04 -0.03 -0.03 -0.01 -0.01 0.00 Licofelone (-1.22,0.29) (-1.00,0.25) (-0.70,0.18) (-0.50,0.22) (-0.49,0.32) (-0.51,0.34) (-0.48,0.34) (-0.47,0.33) (-0.36,0.23) (-0.46,0.35) (-0.29,0.19) (-0.57,0.51) (-0.36,0.28) (-0.42,0.37) (-0.44,0.38) (-0.43,0.42) (-0.41,0.40) (-0.47,0.47)

-0.46 -0.38 -0.26 -0.15 -0.09 -0.09 -0.08 -0.08 -0.07 -0.06 -0.05 -0.03 -0.04 -0.03 -0.03 -0.01 -0.01 0.00 0.00 Risedronate (-1.12,0.20) (-0.87,0.11) (-0.47,-0.05) (-0.33,0.03) (-0.26,0.08) (-0.27,0.09) (-0.21,0.06) (-0.24,0.08) (-0.33,0.19) (-0.18,0.06) (-0.36,0.26) (-0.41,0.34) (-0.41,0.33) (-0.16,0.10) (-0.17,0.10) (-0.20,0.17) (-0.13,0.11) (-0.28,0.26) (-0.40,0.39)

-0.48 -0.39 -0.28 -0.16 -0.11 -0.10 -0.09 -0.09 -0.08 -0.07 -0.06 -0.05 -0.05 -0.04 -0.04 -0.03 -0.03 -0.02 -0.02 -0.01 Zoledronic (-1.33,0.40) (-1.12,0.32) (-0.87,0.33) (-0.73,0.43) (-0.67,0.47) (-0.66,0.48) (-0.65,0.48) (-0.66,0.49) (-0.68,0.52) (-0.63,0.49) (-0.67,0.57) (-0.71,0.63) (-0.70,0.61) (-0.61,0.52) (-0.61,0.52) (-0.61,0.55) (-0.58,0.54) (-0.63,0.61) (-0.68,0.65) (-0.56,0.55) Acid

-0.49 -0.40 -0.29 -0.17 -0.12 -0.11 -0.10 -0.10 -0.09 -0.08 -0.07 -0.06 -0.06 -0.05 -0.06 -0.04 -0.04 -0.03 -0.03 -0.02 -0.01 Diclofenac (-1.18,0.20) (-0.93,0.12) (-0.57,0.00) (-0.31,-0.04) (-0.35,0.11) (-0.38,0.15) (-0.34,0.14) (-0.33,0.12) (-0.24,0.05) (-0.31,0.15) (-0.30,0.15) (-0.49,0.37) (-0.37,0.25) (-0.27,0.15) (-0.3,0.18) (-0.30,0.23) (-0.27,0.19) (-0.37,0.31) (-0.36,0.30) (-0.24,0.20) (-0.60,0.57)

-0.50 -0.41 -0.29 -0.18 -0.13 -0.12 -0.11 -0.11 -0.10 -0.09 -0.08 -0.07 -0.07 -0.06 -0.06 -0.05 -0.04 -0.04 -0.03 -0.03 -0.02 -0.01 Placebo (-1.14,0.16) (-0.90,0.07) (-0.49,-0.09) (-0.35,-0.01) (-0.29,0.03) (-0.29,0.05) (-0.23,0.01) (-0.26,0.04) (-0.35,0.15) (-0.19,0.01) (-0.39,0.23) (-0.44,0.31) (-0.44,0.30) (-0.17,0.05) (-0.18,0.06) (-0.21,0.12) (-0.15,0.06) (-0.3,0.22) (-0.43,0.36) (-0.10,0.03) (-0.58,0.53) (-0.22,0.20)

-0.53 -0.44 -0.33 (-0.6,- -0.22 -0.16 -0.16 -0.14 -0.15 -0.14 -0.13 -0.12 -0.10 -0.11 -0.10 -0.10 -0.08 -0.08 -0.07 -0.07 -0.07 -0.05 -0.04 -0.04 Indomethacin (-1.20,0.15) (-0.97,0.08) 0.05) (-0.47,0.04) (-0.40,0.08) (-0.41,0.10) (-0.37,0.08) (-0.38,0.10) (-0.45,0.18) (-0.34,0.09) (-0.47,0.24) (-0.53,0.31) (-0.51,0.31) (-0.31,0.12) (-0.32,0.12) (-0.27,0.11) (-0.29,0.13) (-0.39,0.25) (-0.50,0.36) (-0.26,0.13) (-0.64,0.53) (-0.32,0.24) (-0.22,0.15)

-0.61 -0.52 -0.41 -0.30 -0.24 -0.23 -0.22 -0.22 -0.22 -0.20 -0.19 -0.18 -0.18 -0.18 -0.18 -0.16 -0.16 -0.15 -0.15 -0.14 -0.13 -0.12 -0.11 -0.08 Rofecoxib (-1.30,0.09) (-1.06,0.00) (-0.71,-0.10) (-0.46,-0.13) (-0.49,0.01) (-0.52,0.05) (-0.48,0.04) (-0.47,0.03) (-0.39,-0.04) (-0.46,0.05) (-0.44,0.05) (-0.62,0.25) (-0.51,0.14) (-0.41,0.05) (-0.44,0.08) (-0.44,0.13) (-0.41,0.09) (-0.50,0.20) (-0.50,0.19) (-0.38,0.10) (-0.73,0.46) (-0.22,-0.03) (-0.34,0.12) (-0.38,0.22)

-0.61 -0.52 -0.41 -0.30 -0.24 -0.24 -0.22 -0.23 -0.22 -0.21 -0.20 -0.18 -0.19 -0.18 -0.18 -0.16 -0.16 -0.15 -0.15 -0.15 -0.13 -0.12 -0.12 -0.08 0.00 HA + MTP (-1.29,0.06) (-1.05,0.00) (-0.74,-0.08) (-0.61,0.01) (-0.55,0.06) (-0.54,0.07) (-0.51,0.06) (-0.52,0.07) (-0.59,0.14) (-0.48,0.07) (-0.60,0.20) (-0.61,0.23) (-0.63,0.27) (-0.46,0.10) (-0.41,0.05) (-0.47,0.15) (-0.44,0.12) (-0.50,0.21) (-0.62,0.32) (-0.42,0.12) (-0.75,0.47) (-0.46,0.21) (-0.38,0.14) (-0.40,0.24) (-0.35,0.34)

-0.67 -0.58 -0.46 -0.35 -0.30 -0.29 -0.28 -0.28 -0.27 -0.26 -0.25 -0.24 -0.24 -0.23 -0.23 -0.22 -0.21 -0.21 -0.20 -0.20 -0.19 -0.18 -0.17 -0.13 -0.06 -0.05 Etofenamate (-1.47,0.15) (-1.29,0.11) (-1.03,0.10) (-0.91,0.19) (-0.85,0.25) (-0.83,0.26) (-0.81,0.25) (-0.82,0.26) (-0.86,0.30) (-0.80,0.27) (-0.85,0.34) (-0.86,0.39) (-0.88,0.40) (-0.77,0.30) (-0.74,0.27) (-0.77,0.33) (-0.75,0.31) (-0.78,0.36) (-0.86,0.44) (-0.73,0.32) (-0.93,0.55) (-0.75,0.38) (-0.69,0.35) (-0.69,0.43) (-0.63,0.51) (-0.61,0.51)

-0.71 -0.62 -0.51 -0.39 -0.34 -0.33 -0.32 -0.32 -0.32 -0.30 -0.29 -0.28 -0.28 -0.28 -0.28 -0.26 -0.26 -0.25 -0.25 -0.24 -0.23 -0.22 -0.21 -0.18 -0.10 -0.10 -0.04 TRM (-1.42,0.01) (-1.18,-0.06) (-0.85,-0.16) (-0.72,-0.06) (-0.66,-0.01) (-0.65,-0.01) (-0.63,-0.02) (-0.64,0.00) (-0.69,0.08) (-0.60,-0.01) (-0.70,0.12) (-0.74,0.18) (-0.74,0.18) (-0.57,0.03) (-0.57,0.03) (-0.59,0.07) (-0.55,0.04) (-0.63,0.14) (-0.73,0.23) (-0.53,0.05) (-0.86,0.37) (-0.57,0.14) (-0.49,0.07) (-0.51,0.16) (-0.46,0.28) (-0.47,0.29) (-0.63,0.54)

-0.71 -0.62 -0.51 -0.40 -0.34 -0.34 -0.32 -0.33 -0.32 -0.31 -0.30 -0.28 -0.29 -0.28 -0.28 -0.26 -0.26 -0.25 -0.25 -0.25 -0.24 -0.23 -0.22 -0.18 -0.10 -0.10 -0.05 0.00 (-0.93,-0.08) Vitamin E (-1.46,0.03) (-1.26,0.00) (-0.81,0.00) (-0.74,0.07) (-0.75,0.08) (-0.71,0.07) (-0.72,0.08) (-0.78,0.13) (-0.69,0.08) (-0.78,0.18) (-0.81,0.25) (-0.81,0.24) (-0.67,0.11) (-0.68,0.12) (-0.67,0.15) (-0.64,0.13) (-0.71,0.20) (-0.79,0.28) (-0.63,0.13) (-0.90,0.42) (-0.66,0.19) (-0.59,0.16) (-0.60,0.24) (-0.55,0.33) (-0.56,0.36) (-0.70,0.61) (-0.47,0.46)

-0.74 -0.65 -0.54 -0.42 -0.37 -0.36 -0.35 -0.35 -0.34 -0.33 -0.32 -0.31 -0.31 -0.31 -0.31 -0.29 -0.29 -0.28 -0.28 -0.27 -0.26 -0.25 -0.24 -0.21 -0.13 -0.13 -0.07 -0.03 -0.03 ACT (-1.64,0.12) (-1.41,0.12) (-1.18,0.09) (-1.02,0.16) (-0.99,0.25) (-1.00,0.27) (-0.97,0.27) (-0.97,0.26) (-0.89,0.21) (-0.96,0.28) (-0.85,0.20) (-1.03,0.40) (-0.88,0.25) (-0.92,0.30) (-0.93,0.30) (-0.92,0.33) (-0.90,0.33) (-0.94,0.39) (-0.85,0.28) (-0.89,0.33) (-1.07,0.53) (-0.83,0.32) (-0.85,0.36) (-0.85,0.43) (-0.72,0.45) (-0.80,0.52) (-0.88,0.70) (-0.70,0.64) (-0.73,0.67)

-1.02 -0.93 -0.81 -0.70 -0.65 -0.64 -0.63 -0.63 -0.62 -0.61 -0.60 -0.59 -0.59 -0.58 -0.58 -0.57 -0.56 -0.56 -0.55 -0.55 -0.54 -0.53 -0.52 -0.48 -0.41 -0.40 -0.35 -0.31 -0.30 -0.28 (-1.13,-0.49) Sprifermin (-1.71,-0.31) (-1.48,-0.36) (-1.01,-0.39) (-0.94,-0.34) (-0.94,-0.34) (-0.91,-0.34) (-0.93,-0.34) (-0.98,-0.26) (-0.88,-0.34) (-1.00,-0.20) (-1.04,-0.13) (-1.04,-0.14) (-0.87,-0.30) (-0.87,-0.30) (-0.87,-0.26) (-0.84,-0.29) (-0.92,-0.20) (-1.02,-0.09) (-0.82,-0.28) (-1.16,0.08) (-0.85,-0.20) (-0.78,-0.26) (-0.80,-0.17) (-0.74,-0.07) (-0.77,-0.04) (-0.94,0.24) (-0.69,0.07) (-0.78,0.15) (-0.92,0.38)

-2.06 -1.97 -1.86 -1.75 -1.69 -1.69 -1.67 -1.68 -1.67 -1.66 -1.65 -1.63 -1.64 -1.63 -1.63 -1.61 -1.61 -1.60 -1.60 -1.60 -1.59 -1.57 -1.57 -1.53 -1.45 -1.45 -1.40 -1.35 -1.35 -1.32 -1.05 (-2.23,-1.48) (-1.88,-1.25) BMS (-2.76,-1.36) (-2.53,-1.42) (-2.10,-1.38) (-2.05,-1.34) (-2.04,-1.34) (-2.01,-1.34) (-2.03,-1.32) (-2.07,-1.26) (-1.99,-1.33) (-2.08,-1.20) (-2.09,-1.17) (-2.11,-1.15) (-1.96,-1.30) (-1.92,-1.34) (-1.96,-1.26) (-1.94,-1.28) (-1.99,-1.20) (-2.1,-1.09) (-1.92,-1.28) (-2.22,-0.95) (-1.95,-1.20) (-1.89,-1.17) (-1.85,-1.06) (-1.82,-1.08) (-1.99,-0.81) (-1.77,-0.94) (-1.85,-0.87) (-2.00,-0.63) (-1.45,-0.64)

@2018 American Medical Association. All rights reserved. 33 s Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 678 eTable 5 – Physical function (secondary outcome): league table 679 Treatments in diagonal cells are reported in order of relative ranking for efficacy. Direct comparisons are reported in light grey cells, while significant estimates 680 are presented in bold. Comparisons between treatments read from left to right: a network estimate less than 0 indicates that treatment reported in column is more 681 effective than corresponding treatment reported in row. Point estimates refer to the posterior mean. CS Chondroitin Sulfate. Glucosamine Sulfate -0.16 Vitamin D (-0.43,0.11) -0.19 -0.03 Celecoxib (-0.47,0.09) (-0.29,0.23) -0.20 -0.04 -0.01 Calcitonin (-0.45,0.04) (-0.26,0.18) (-0.25,0.23) -0.24 -0.08 -0.04 -0.03 Strontium (-0.46,-0.01) (-0.28,0.13) (-0.27,0.18) (-0.21,0.14) Ranelate -0.28 -0.12 -0.09 -0.08 -0.05 Glucosamine (-0.54,-0.02) (-0.36,0.11) (-0.29,0.11) (-0.29,0.13) (-0.24,0.15) s -0.29 -0.13 -0.10 -0.08 -0.05 -0.01 Chondroitin (-0.55,-0.03) (-0.37,0.11) (-0.28,0.08) (-0.3,0.13) (-0.25,0.15) (-0.18,0.16) Sulfate (CS) -0.29 -0.13 -0.10 -0.09 -0.05 -0.01 0.00 Cindunistat (-0.52,-0.06) (-0.33,0.07) (-0.32,0.13) (-0.26,0.09) (-0.21,0.10) (-0.20,0.18) (-0.20,0.20) -0.30 -0.14 -0.11 -0.09 -0.06 -0.02 -0.01 -0.01 Glucosamine (-0.56,-0.03) (-0.38,0.10) (-0.31,0.10) (-0.31,0.12) (-0.27,0.14) (-0.19,0.16) (-0.18,0.16) (-0.21,0.19) s + CS -0.30 -0.14 -0.11 -0.10 -0.07 -0.02 -0.01 -0.01 0.00 Risedronate (-0.51,-0.09) (-0.33,0.05) (-0.32,0.10) (-0.25,0.05) (-0.20,0.06) (-0.19,0.15) (-0.19,0.16) (-0.14,0.12) (-0.19,0.18) -0.32 -0.16 -0.13 -0.11 -0.08 -0.04 -0.03 -0.03 -0.02 -0.02 Placebo (-0.52,-0.12) (-0.33,0.02) (-0.32,0.07) (-0.25,0.02) (-0.19,0.03) (-0.20,0.12) (-0.20,0.14) (-0.13,0.08) (-0.19,0.15) (-0.08,0.05) -0.39 -0.23 -0.20 -0.19 -0.16 -0.11 -0.10 -0.10 -0.09 -0.09 -0.07 Triamcinolon (-0.74,-0.04) (-0.56,0.10) (-0.54,0.15) (-0.50,0.13) (-0.45,0.15) (-0.43,0.22) (-0.42,0.22) (-0.40,0.20) (-0.42,0.24) (-0.38,0.20) (-0.35,0.21) e -0.56 -0.40 -0.37 -0.36 -0.33 -0.28 -0.27 -0.27 -0.26 -0.26 -0.24 -0.17 Vitamin E (-0.99,-0.14) (-0.81,0.01) (-0.79,0.06) (-0.76,0.04) (-0.71,0.07) (-0.69,0.13) (-0.68,0.14) (-0.66,0.12) (-0.68,0.15) (-0.64,0.12) (-0.62,0.13) (-0.65,0.29) -0.64 -0.48 -0.45 -0.44 -0.40 -0.36 -0.35 -0.35 -0.34 -0.34 -0.32 -0.25 -0.08 Sprifermin (-0.97,-0.31) (-0.79,-0.17) (-0.77,-0.12) (-0.72,-0.14) (-0.68,-0.12) (-0.66,-0.05) (-0.66,-0.04) (-0.63,-0.07) (-0.65,-0.03) (-0.60,-0.07) (-0.58,-0.06) (-0.62,0.14) (-0.53,0.38) 682

683

684

685

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 686 eTable 6 – Physical function (secondary outcome): summary table of results when 687 trials at high risk of bias were excluded and only high quality (HQ) were analysed. 688 689 Data are standardized mean differences (SMDs) and 95% credibility interval (Crl). 690 Outcome Treatment Main analysis HQ trials FUNCTION Calcitonin -0.11 (-0.25,0.02) -0.11 (-0.25,0.02) Celecoxib -0.13 (-0.32,0.07) -0.10 (-0.31,0.10) Chondroitin Sulfate -0.03 (-0.20,0.14) 0.00 (-0.18,0.17) Cindunistat -0.03 (-0.13,0.08) -0.03 (-0.13,0.08) Glucosamines -0.04 (-0.20,0.12) 0.01 (-0.17,0.18) Glucosamines + CS -0.02 (-0.19,0.15) 0.01 (-0.17,0.19) Glucosamine Sulfate -0.32 (-0.52,-0.12) -0.32 (-0.52,-0.11) Risedronate -0.02 (-0.08,0.05) -0.02 (-0.09,0.05) Sprifermin 0.32 (0.06,0.58) 0.32 (0.06,0.58) Strontium Ranelate -0.08 (-0.19,0.03) -0.08 (-0.19,0.03) Triamcinolone 0.07 (-0.21,0.35) 0.08 (-0.26,0.42) Vitamin E 0.24 (-0.13,0.62) 0.24 (-0.13,0.62) Vitamin D -0.16 (-0.33,0.02) -0.16 (-0.33,0.01) 691

692 693

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 714 eTable 7 - Joint space narrowing (secondary outcome): summary table of results 715 reported as Mean Difference (in mm) and as Standardized Mean Difference 716 717 For consistency with the primary outcome (pain) and the first secondary outcome (physical function), that are 718 reported on different scales in the different studies, also the secondary outcome JSN has been reported in 719 the manuscript as SMD. However, as JSN is reported on a single scale (mm) in the considered studies, the 720 meta-analysis procedure has been also repeated using the Mean Difference for the JSN secondary 721 endpoint, for an easier interpretability of the results. 722 Main analysis Additional analysis Standardized Mean Mean Difference Outcome Treatment Difference in mm (95% CrI) (95% Crl) JSN Calcitonin 0.04 (-0.16,0.24) 0.03 (-0.12,0.17) Celecoxib 0.11 (-0.19,0.41) 0.11 (-0.82,1.06) Chondroitin Sulfate 0.20 (0.07,0.31) 0.16 (0.07,0.25) Cindunistat 0.03 (-0.12,0.18) 0.02 (-0.09,0.14) Diclofenac -0.20 (-0.71,0.31) -0.15 (-0.56,0.26) Doxycycline 0.21 (-0.05,0.48) 0.15 (-0.03,0.33) Glucosamines 0.07 (-0.11,0.26) 0.10 (-0.06,0.26) Glucosamines + CS 0.18 (-0.03,0.39) 0.19 (0.00,0.36) Glucosamine Sulfate 0.42 (0.19,0.65) 0.27 (0.12,0.42) Hyaluronic Acid 0.26 (-0.42,0.93) 0.04 (-0.21,0.30) MMP Inhibitors -0.06 (-0.24,0.13) -0.03 (-0.14,0.08) Risedronate 0.05 (-0.15,0.26) 0.17 (-0.14,0.47) Sprifermin 0.03 (-0.25,0.30) 0.03 (-0.21,0.27) Strontium Ranelate 0.20 (0.05,0.36) 0.12 (0.01,0.23) Triamcinolone 0.01 (-0.50,0.52) 0.01 (-1.94,1.99) Vitamin D 0.11 (-0.11,0.31) 0.07 (-0.12,0.26) 723

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 745 eTable 8 - Joint space narrowing (secondary outcome): league table 746 Treatments in diagonal cells are reported in order of relative ranking for efficacy. Direct comparisons are reported in light grey cells, while significant estimates are presented 747 in bold. Comparisons between treatments read from left to right: a network estimate less than 0 indicates that treatment reported in column is mor e effective than 748 corresponding treatment reported in row. Point estimates refer to the posterior mean. CS Chondroitin Sulfate; MMP Inhibitors Matrix Metalloproteinase Inhibitors. Glucosamine Sulfate 0.16 Hyaluronic (-0.55,0.87) Acid 0.21 0.04 Doxycycline (-0.14,0.56) (-0.69,0.77)

0.22 0.06 0.02 Chondroitin Sulfate (-0.03,0.48) (-0.63,0.75) (-0.27,0.31) (CS) 0.22 0.05 0.01 -0.01 Strontium (-0.06,0.49) (-0.64,0.75) (-0.30,0.31) (-0.21,0.18) Ranelate 0.24 0.07 0.03 0.02 0.02 Glucosamines (-0.07,0.55) (-0.63,0.79) (-0.31,0.38) (-0.20,0.23) (-0.23,0.29) + CS 0.31 0.14 0.10 0.09 0.09 0.07 Celecoxib (-0.07,0.69) (-0.59,0.88) (-0.30,0.50) (-0.21,0.39) (-0.24,0.43) (-0.25,0.40) 0.31 0.15 0.11 0.09 0.10 0.08 0.01 Vitamin D (0.01,0.63) (-0.56,0.86) (-0.22,0.46) (-0.15,0.34) (-0.15,0.37) (-0.22,0.38) (-0.36,0.37) 0.35 0.18 0.14 0.13 0.13 0.11 0.04 0.03 Glucosamines (0.05,0.64) (-0.52,0.89) (-0.18,0.47) (-0.07,0.32) (-0.11,0.37) (-0.12,0.34) (-0.27,0.34) (-0.25,0.31) 0.37 0.21 0.16 0.15 0.15 0.13 0.06 0.05 0.02 Risedronate (0.06,0.67) (-0.50,0.91) (-0.18,0.50) (-0.09,0.38) (-0.11,0.41) (-0.16,0.42) (-0.30,0.42) (-0.25,0.34) (-0.24,0.28) 0.38 0.21 0.17 0.15 0.16 0.14 0.07 0.06 0.03 0.01 Calcitonin (0.08,0.68) (-0.49,0.92) (-0.16,0.50) (-0.09,0.38) (-0.09,0.41) (-0.16,0.43) (-0.29,0.43) (-0.24,0.34) (-0.25,0.30) (-0.27,0.29) 0.39 0.23 0.18 0.17 0.17 0.15 0.08 0.08 0.04 0.02 0.01 Cindunistat (0.12,0.66) (-0.46,0.92) (-0.12,0.49) (-0.03,0.35) (-0.04,0.39) (-0.11,0.41) (-0.25,0.41) (-0.19,0.33) (-0.20,0.28) (-0.23,0.28) (-0.24,0.27) 0.39 0.23 0.19 0.17 0.18 0.15 0.08 0.08 0.05 0.02 0.02 0.00 Sprifermin (0.03,0.75) (-0.50,0.97) (-0.20,0.57) (-0.13,0.47) (-0.14,0.49) (-0.20,0.50) (-0.33,0.50) (-0.27,0.42) (-0.29,0.38) (-0.32,0.37) (-0.32,0.36) (-0.31,0.32) 0.41 0.25 0.21 0.19 0.20 0.17 0.10 0.10 0.06 0.04 0.04 0.02 0.02 Triamcinolone (-0.15,0.97) (-0.59,1.10) (-0.37,0.78) (-0.34,0.71) (-0.34,0.72) (-0.38,0.73) (-0.49,0.70) (-0.46,0.65) (-0.48,0.61) (-0.51,0.59) (-0.51,0.58) (-0.51,0.55) (-0.57,0.60) 0.42 0.26 0.21 0.20 0.20 0.18 0.11 0.11 0.07 0.05 0.04 0.03 0.03 0.01 Placebo (0.19,0.65) (-0.42,0.93) (-0.05,0.48) (0.07,0.31) (0.05,0.36) (-0.03,0.39) (-0.19,0.41) (-0.11,0.31) (-0.11,0.26) (-0.15,0.26) (-0.16,0.24) (-0.12,0.18) (-0.25,0.30) (-0.50,0.52) 0.47 0.31 0.27 0.25 0.26 0.24 0.17 0.16 0.13 0.11 0.10 0.08 0.08 0.06 0.06 MMP (0.18,0.77) (-0.39,1.02) (-0.06,0.60) (0.03,0.47) (0.02,0.5) (-0.05,0.52) (-0.19,0.52) (-0.13,0.44) (-0.14,0.39) (-0.17,0.39) (-0.18,0.37) (-0.15,0.32) (-0.25,0.42) (-0.47,0.60) (-0.13,0.24) Inhibitors 0.62 0.46 0.42 0.40 0.41 0.39 0.32 0.31 0.28 0.26 0.25 0.23 0.23 0.21 0.20 0.15 Diclofenac (0.06,1.18) (-0.39,1.32) (-0.16,1.00) (-0.13,0.93) (-0.13,0.94) (-0.18,0.94) (-0.28,0.92) (-0.25,0.85) (-0.28,0.82) (-0.30,0.80) (-0.31,0.80) (-0.31,0.77) (-0.36,0.82) (-0.51,0.93) (-0.31,0.71) (-0.40,0.69)

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 749 750 eTable 9 - Joint space narrowing (secondary outcome): summary table of 751 results when trials at high risk of bias were excluded and only high quality 752 (HQ) were analysed. 753 754 Outcome Treatment Main analysis Additional Additional Additional Standardized analysis analysis analysis Mean Difference Standardized Mean Difference Mean Difference (95% CrI) Mean Difference in mm in mm All trials (95% Crl) (95% CrI) (95% Crl) HQ trials All trials HQ trials JSN Calcitonin 0.04 (-0.16,0.24) 0.04 (-0.16,0.24) 0.03 (-0.12,0.17) 0.03 (-0.12,0.18) Celecoxib 0.11 (-0.19,0.41) 0.12 (-0.18,0.42) 0.11 (-0.82,1.06) 0.12 (-0.84,1.13) Chondroitin Sulfate 0.20 (0.07,0.31) 0.23 (0.09,0.36) 0.16 (0.07,0.25) 0.16 (0.06,0.25) Cindunistat 0.03 (-0.12,0.18) 0.03 (-0.12,0.18) 0.02 (-0.09,0.14) 0.02 (-0.09,0.14) Diclofenac -0.20 (-0.71,0.31) -0.21 (-0.72,0.30) -0.15 (-0.56,0.26) -0.15 (-0.55,0.25) Doxycycline 0.21 (-0.05,0.48) 0.21 (-0.05,0.48) 0.15 (-0.03,0.33) 0.15 (-0.04,0.33) Glucosamines 0.07 (-0.11,0.26) 0.07 (-0.14,0.28) 0.10 (-0.06,0.26) 0.02 (-0.17,0.21) Glucosamines+CS 0.18 (-0.03,0.39) 0.20 (-0.02,0.41) 0.19 (0.00,0.36) 0.17 (-0.02,0.35) Glucosamine Sulfate 0.42 (0.19,0.65) 0.42 (0.20,0.65) 0.27 (0.12,0.42) 0.26 (0.11,0.42) Hyaluronic Acid 0.26 (-0.42,0.93) 0.00 (-0.29,0.29) 0.04 (-0.21,0.30) 0.00 (-0.27,0.27) MMP Inhibitors -0.06 (-0.24,0.13) -0.06 (-0.24,0.13) -0.03 (-0.14,0.08) -0.03 (-0.14,0.08) Risedronate 0.05 (-0.15,0.26) 0.01 (-0.22,0.24) 0.17 (-0.14,0.47) 0.05 (-0.69,0.79) Sprifermin 0.03 (-0.25,0.30) 0.03 (-0.25,0.31) 0.03 (-0.21,0.27) 0.03 (-0.21,0.27) Strontium Ranelate 0.20 (0.05,0.36) 0.20 (0.05,0.35) 0.12 (0.01,0.23) 0.12 (0.01,0.23) Triamcinolone 0.01 (-0.50,0.52) - 0.01 (-1.94,1.99) - Vitamin D 0.11 (-0.11,0.31) 0.10 (-0.11,0.30) 0.07 (-0.12,0.26) 0.08 (-0.11,0.26) 755

756

757

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 758 759 eTable10 A - Summary of results for the sensitivity analyses, including 760 clinical and statistical sensitivities. 761 Data are standardized mean differences (SMDs) and 95% credibility interval (Crl) No maximum SD Intra-articular No maximum SD Outcome Treatment Main analysis Oral placebo Blinded studies and correlation placebo imputation imputation PAIN Acetaminophen 0.24 (-0.36,0.85) 0.26 (-0.34,0.86) - 0.27 (-0.33,0.86) - - Betamethasone 1.57 (1.25,1.88) 1.30 (0.57,2.02) 1.69 (1.30,2.08) - 1.50 (1.17,1.83) Calcitonin -0.11 (-0.23,0.01) -0.11 (-0.23,0.01) - -0.11 (-0.23,0.01) -0.11 (-0.23,0.02) -0.11 (-0.24,0.03) Celecoxib -0.18 (-0.35,-0.01) -0.18 (-0.35,0.00) - -0.16 (-0.33,0.01) -0.21 (-0.48,0.07) -0.28 (-0.64,0.07) Chondroitin Sulfate (CS) -0.06 (-0.17,0.05) -0.06 (-0.17,0.05) - -0.05 (-0.16,0.06) -0.09 (-0.22,0.03) -0.07 (-0.26,0.10) Cindunistat -0.04 (-0.15,0.06) -0.04 (-0.15,0.06) - -0.04 (-0.14,0.06) -0.04 (-0.15,0.06) -0.04 (-0.15,0.06) Diacerein -0.04 (-0.30,0.22) - -0.03 (-0.36,0.30) -0.03 (-0.29,0.23) -0.07 (-0.34,0.20) -0.05 (-0.35,0.25) Diclofenac -0.01 (-0.22,0.20) 0.00 (-0.22,0.21) - 0.01(-0.19,0.22) -0.03 (-0.32,0.26) - Etofenamate 0.17 (-0.35,0.69) -0.08 (-0.88,0.75) 0.18 (-0.40,0.77) - 0.12 (-0.42,0.66) Etoricoxib -0.10 (-0.35,0.15) -0.10 (-0.36,0.16) - -0.08 (-0.33,0.18) - - Glucosamines -0.11 (-0.26,0.04) -0.11 (-0.26,0.04) - -0.07 (-0.23,0.08) -0.13 (-0.32,0.06) -0.34 (-0.73,0.06) Glucosamines + CS -0.13 (-0.29,0.03) -0.12 (-0.28,0.03) - -0.11 (-0.27,0.04) -0.19 (-0.41,0.01) - Glucosamine Sulfate -0.29 (-0.49,-0.09) -0.29 (-0.49,-0.09) - -0.30 (-0.50,-0.10) -0.29 (-0.49,-0.10) -0.29 (-0.49,-0.09) Hyaluronic Acid (HA) -0.06 (-0.18,0.06) -0.32 (-0.98,0.35) -0.06 (-0.21,0.10) -0.04 (-0.17,0.08) -0.12 (-0.27,0.03) -0.08 (-0.30,0.15) HA + Betamethasone -0.41 (-0.90,0.07) -0.65 (-1.46,0.15) -0.42 (-0.96,0.12) - -0.45 (-0.95,0.04) HA + Methylprednisolone 0.12 (-0.14,0.38) -0.14 (-0.83,0.55) 0.13 (-0.22,0.48) - - - HA + Triamcinolone -0.50 (-1.14,0.16) -0.76 (-1.68,0.17) -0.55 (-1.23,0.14) -0.47 (-1.12,0.18) - - Indomethacin 0.04 (-0.15,0.22) 0.03 (-0.16,0.23) - 0.03 (-0.16,0.22) - - Licofelone -0.03 (-0.43,0.36) -0.03 (-0.42,0.36) - -0.01 (-0.40,0.38) - - Methylprednisolone -0.07 (-0.44,0.31) -0.32 (-1.07,0.42) -0.06 (-0.50,0.39) - -0.12 (-0.51,0.27) Naproxen -0.08 (-0.39,0.23) -0.07 (-0.39,0.24) - -0.06 (-0.36,0.25) - - Nimesulide -0.07 (-0.44,0.30) -0.06 (-0.44,0.32) - -0.05 (-0.42,0.33) - - Risedronate -0.03 (-0.10,0.03) -0.03 (-0.10,0.03) - -0.04 (-0.10,0.03) -0.03 (-0.10,0.04) -0.03 (-0.10,0.04) Rofecoxib 0.11 (-0.12,0.34) 0.12 (-0.11,0.35) - 0.13 (-0.09,0.37) 0.08 (-0.23,0.40) - Sprifermin 0.52 (0.26,0.78) - 0.52 (0.23,0.81) 0.52 (0.26,0.77) 0.52 (0.26,0.78) 0.52 (0.26,0.78) Strontium Ranelate -0.09 (-0.19,0.01) -0.09 (-0.20,0.01) - -0.09 (-0.19,0.01) -0.09 (-0.20,0.01) -0.09 (-0.20,0.02) Tiaprofenic Acid -0.05 (-0.21,0.12) -0.05 (-0.22,0.13) - -0.05 (-0.22,0.12) - - Triamcinolone 0.21 (-0.07,0.49) - 0.20 (-0.11,0.52) 0.21 (-0.06,0.49) 0.21 (-0.08,0.49) 0.21 (-0.08,0.49) Vitamin E 0.22 (-0.16,0.59) 0.22 (-0.15,0.59) - 0.22 (-0.15,0.58) 0.22 (-0.16,0.59) 0.22 (-0.15,0.59) Vitamin D -0.12 (-0.29,0.05) -0.12 (-0.29,0.04) - -0.13 (-0.29,0.04) -0.12 (-0.29,0.05) -0.23 (-0.56,0.11) Zoledronic Acid -0.02 (-0.58,0.53) -0.02 (-0.57,0.53) - -0.02 (-0.55,0.52) -0.02 (-0.57,0.55) - FUNCTION Calcitonin -0.11 (-0.25,0.02) -0.11 (-0.25,0.02) - -0.11 (-0.25,0.02) -0.11 (-0.26,0.03) -0.11 (-0.25,0.03) Celecoxib -0.13 (-0.32,0.07) -0.13 (-0.33,0.07) - -0.10 (-0.31,0.10) -0.30 (-0.69,0.08) - Chondroitin Sulfate -0.03 (-0.20,0.14) -0.03 (-0.20,0.14) - -0.01 (-0.18,0.16) -0.12 (-0.36,0.11) - Cindunistat -0.03 (-0.13,0.08) -0.03 (-0.14,0.08) - -0.03 (-0.13,0.08) -0.03 (-0.14,0.09) -0.03 (-0.14,0.08) Glucosamines -0.04 (-0.20,0.12) -0.03 (-0.20,0.12) 0.01 (-0.17,0.18) -0.07 (-0.28,0.14) -0.26 (-0.66,0.13) Glucosamines + CS -0.02 (-0.19,0.15) -0.02 (-0.19,0.16) - -0.00 (-0.17,0.18) -0.11 (-0.35,0.12) - Glucosamine Sulfate -0.32 (-0.52,-0.12) -0.31 (-0.52,-0.11) - -0.32 (-0.52,-0.12) -0.32 (-0.52,-0.11) -0.32 (-0.52,-0.11) Risedronate -0.02 (-0.08,0.05) -0.02 (-0.09,0.05) - -0.02 (-0.09,0.05) -0.02 (-0.09,0.05) -0.02 (-0.09,0.05) Sprifermin 0.32 (0.06,0.58) - 0.31 (-0.18,0.77) 0.32 (0.06,0.59) 0.32 (0.06,0.58) 0.32 (0.06,0.58) Strontium Ranelate -0.08 (-0.19,0.03) -0.08 (-0.19,0.03) - -0.08 (-0.19,0.03) -0.08 (-0.20,0.03) -0.08 (-0.19,0.03) Triamcinolone 0.07 (-0.21,0.35) - 0.07 (-0.50,0.64) 0.07 (-0.21,0.35) 0.07 (-0.21,0.36) 0.08 (-0.21,0.36) Vitamin E 0.24 (-0.13,0.62) 0.24 (-0.14,0.61) - 0.24 (-0.13,0.61) 0.24 (-0.13,0.62) 0.24 (-0.14,0.61) Vitamin D -0.16 (-0.33,0.02) -0.16 (-0.33,0.01) - -0.16 (-0.33,0.01) -0.16 (-0.33,0.01) -0.37 (-0.71,-0.03) JSN Calcitonin 0.04 (-0.16,0.24) 0.04 (-0.16,0.25) - 0.04 (-0.17,0.26) 0.04 (-0.14,0.23) 0.04 (-0.12,0.20) Celecoxib 0.11 (-0.19,0.41) 0.12 (-0.18,0.41) - 0.10 (-0.20,0.41) - - Chondroitin Sulfate 0.20 (0.07,0.31) 0.21 (0.08,0.33) - 0.19 (0.06,0.31) 0.27 (0.13,0.40) 0.32 (0.18,0.46) Cindunistat 0.03 (-0.12,0.18) 0.03 (-0.12,0.18) - 0.03 (-0.13,0.19) 0.03 (-0.11,0.17) 0.03 (-0.09,0.15) Diclofenac -0.20 (-0.71,0.31) -0.21 (-0.71,0.31) - -0.21 (-0.72,0.30) -0.21 (-0.72,0.31) - Doxycycline 0.21 (-0.05,0.48) 0.21 (-0.05,0.48) - 0.21 (-0.06,0.49) 0.22 (-0.04,0.47) 0.21 (-0.03,0.45) Glucosamines 0.07 (-0.11,0.26) 0.08 (-0.11,0.27) - 0.05 (-0.17,0.26) 0.07 (-0.16,0.29) 0.17 (-0.25,0.59) Glucosamines + CS 0.18 (-0.03,0.39) 0.19 (-0.02,0.40) - 0.18 (-0.05,0.39) 0.27 (0.01,0.53) - Glucosamine Sulfate 0.42 (0.19,0.65) 0.42 (0.19,0.65) - 0.42 (0.19,0.65) 0.42 (0.20,0.64) 0.42 (0.21,0.63) Hyaluronic Acid 0.26 (-0.42,0.93) 0.25 (-0.43,0.93) 0.00 (-0.74,0.73) 0.00 (-0.30,0.30) 0.04 (-0.22,0.30) 0.25 (-0.43,0.93) MM Inhibitors -0.06 (-0.24,0.13) -0.06 (-0.24,0.13) - -0.05 (-0.25,0.14) -0.05 (-0.24,0.13) -0.05 (-0.23,0.13) Risedronate 0.05 (-0.15,0.26) 0.05 (-0.15,0.26) - 0.01 (-0.23,0.25) 0.05 (-0.15,0.25) 0.06 (-0.14,0.26) Sprifermin 0.03 (-0.25,0.30) - 0.03 (-0.47,0.54) 0.03 (-0.25,0.31) 0.03 (-0.25,0.31) 0.03 (-0.24,0.30) Strontium Ranelate 0.20 (0.05,0.36) 0.2 (0.05,0.36) - 0.20 (0.04,0.36) 0.20 (0.06,0.35) 0.20 (0.08,0.33) Triamcinolone 0.01 (-0.50,0.52) - 0.00 (-0.80,0.80) 0.01 (-0.51,0.53) 0.00 (-0.49,0.51) - Vitamin D 0.11 (-0.11,0.31) 0.10 (-0.12,0.29) - 0.10(-0.12,0.30) 0.10 (-0.11,0.29) -0.17 (-0.51,0.17) 762 For the Main analysis the posterior median values of the between-study standard deviations [95% CrI] are: 763 Pain 0.021 [0.001;0.070] 764 Function 0.029 [0.014 ; 0.097] 765 JSN 0.070 [0.005; 0.160].

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 766 eTable 10B1 Post-hoc sensitivity analysis using a Fixed effect model 767 instead of the Random effect model used as main analysis 768 769 The present network meta-analysis has been conducted according to a Bayesian multiple treatment 770 approach, with random effect and uninformative prior. Random effect (RE) approach to meta-analysis is in 771 general considered more conservative than fixed effects, and the choice on RE was a-priori, irrespectively 772 from the observed heterogeneity. Indeed, “FE models, but not RE models, yield confidence intervals for 773 mean effect sizes that are narrower than their nominal width, thereby overstating the degree of precision in 774 meta‐analysis findings. …. these biases in FE procedures are large enough to create serious distortions in 775 conclusions about cumulative knowledge in the research literature. We therefore recommend that RE 776 methods routinely be employed in meta‐analysis in preference to FE methods.”2. 777 A sensitivity analysis based on a Fixed effect model has been conducted for each outcome. 778 The overall relative estimates of the comparisons with placebo are similar to those coming from the Random 779 effect model: results are presented in the eTable below. 780

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 781 eTable 10B1 – Random vs Fixed effect model 782 For fixed effect model: Pain DIC 196.8 - Function DIC 94.19 - Joint Space DIC 114.53 783 Data are standardized mean differences (SMDs) and 95% credibility interval (Crl) Outcome Treatment Main analysis Sensitivity analysis (Random effect model) (Fixed effect model) PAIN Acetaminophen 0.24 (-0.36,0.85) 0.25 (-0.34,0.83) Betamethasone 1.57 (1.25,1.88) 1.56 (1.26,1.87) Calcitonin -0.11 (-0.23,0.01) -0.11 (-0.21,-0.01) Celecoxib -0.18 (-0.35,-0.01) -0.18 (-0.34,-0.01) Chondroitin Sulfate (CS) -0.06 (-0.17,0.05) -0.06 (-0.17,0.05) Cindunistat -0.04 (-0.15,0.06) -0.04 (-0.13,0.05) Diacerein -0.04 (-0.30,0.22) -0.04 (-0.30,0.22) Diclofenac -0.01 (-0.22,0.20) 0.00 (-0.20,0.19) Etofenamate 0.17 (-0.35,0.69) 0.17 (-0.35,0.69) Etoricoxib -0.10 (-0.35,0.15) -0.10 (-0.34,0.15) Glucosamines -0.11 (-0.26,0.04) -0.11 (-0.25,0.03) Glucosamines + CS -0.13 (-0.29,0.03) -0.12 (-0.28,0.03) Glucosamine Sulfate -0.29 (-0.49,-0.09) -0.29 (-0.48,-0.10) Hyaluronic Acid (HA) -0.06 (-0.18,0.06) -0.07 (-0.18,0.05) HA + Betamethasone -0.41 (-0.90,0.07) -0.40 (-0.89,0.08) HA + Methylprednisolone 0.12 (-0.14,0.38) 0.11 (-0.13,0.36) HA + Triamcinolone -0.50 (-1.14,0.16) -0.50 (-1.15,0.14) Indomethacin 0.04 (-0.15,0.22) 0.03 (-0.14,0.21) Licofelone -0.03 (-0.43,0.36) -0.03 (-0.40,0.34) Methylprednisolone -0.07 (-0.44,0.31) -0.06 (-0.43,0.30) Naproxen -0.08 (-0.39,0.23) -0.08 (-0.37,0.22) Nimesulide -0.07 (-0.44,0.30) -0.06 (-0.42,0.29) Risedronate -0.03 (-0.10,0.03) -0.03 (-0.09,0.03) Rofecoxib 0.11 (-0.12,0.34) 0.12 (-0.10,0.33) Sprifermin 0.52 (0.26,0.78) 0.52 (0.26,0.77) Strontium Ranelate -0.09 (-0.19,0.01) -0.09 (-0.18,0.00) Tiaprofenic Acid -0.05 (-0.21,0.12) -0.05 (-0.21,0.11) Triamcinolone 0.21 (-0.07,0.49) 0.21 (-0.06,0.48) Vitamin E 0.22 (-0.16,0.59) 0.22 (-0.14,0.58) Vitamin D -0.12 (-0.29,0.05) -0.12 (-0.28,0.04) Zoledronic Acid -0.02 (-0.58,0.53) -0.02 (-0.56,0.52) FUNCTION Calcitonin -0.11 (-0.25,0.02) -0.11 (-0.22,-0.01) Celecoxib -0.13 (-0.32,0.07) -0.12 (-0.31,0.07) Chondroitin Sulfate -0.03 (-0.20,0.14) -0.03 (-0.18,0.13) Cindunistat -0.03 (-0.13,0.08) -0.03 (-0.12,0.06) Glucosamines -0.04 (-0.20,0.12) -0.03 (-0.19,0.12) Glucosamines + CS -0.02 (-0.19,0.15) -0.02 (-0.18,0.14) Glucosamine Sulfate -0.32 (-0.52,-0.12) -0.32 (-0.51,-0.13) Risedronate -0.02 (-0.08,0.05) -0.02 (-0.08,0.04) Sprifermin 0.32 (0.06,0.58) 0.32 (0.07,0.58) Strontium Ranelate -0.08 (-0.19,0.03) -0.08 (-0.17,0.01) Triamcinolone 0.07 (-0.21,0.35) 0.07 (-0.20,0.35) Vitamin E 0.24 (-0.13,0.62) 0.24 (-0.12,0.61) Vitamin D -0.16 (-0.33,0.02) -0.15 (-0.31,0.01) JSN Calcitonin 0.04 (-0.16,0.24) 0.04 (-0.06,0.15) Celecoxib 0.11 (-0.19,0.41) 0.12 (-0.14,0.38) Chondroitin Sulfate 0.20 (0.07,0.31) 0.22 (0.12,0.31) Cindunistat 0.03 (-0.12,0.18) 0.03 (-0.06,0.12) Diclofenac -0.20 (-0.71,0.31) -0.21 (-0.68,0.28) Doxycycline 0.21 (-0.05,0.48) 0.21 (0.01,0.42) Glucosamines 0.07 (-0.11,0.26) 0.07 (-0.09,0.24) Glucosamines + CS 0.18 (-0.03,0.39) 0.20 (0.01,0.38) Glucosamine Sulfate 0.42 (0.19,0.65) 0.42 (0.23,0.61) Hyaluronic Acid 0.26 (-0.42,0.93) 0.03 (-0.19,0.25) MM Inhibitors -0.06 (-0.24,0.13) -0.05 (-0.23,0.12) Risedronate 0.05 (-0.15,0.26) 0.05 (-0.13,0.22) Sprifermin 0.03 (-0.25,0.30) 0.03 (-0.23,0.29) Strontium Ranelate 0.20 (0.05,0.36) 0.20 (0.11,0.29) Triamcinolone 0.01 (-0.50,0.52) 0.01 (-0.48,0.49) Vitamin D 0.11 (-0.11,0.31) 0.12 (-0.04,0.28) 784

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 785

786 eTable 10B2 Post-hoc sensitivity analysis using an empirical informative 787 prior instead of the uninformative prior used as main analysis 788

789 A sensitivity analysis has been conducted for each outcome based on an empirical informative prior on 790 heterogeneity distribution: specifically, a log-t distribution t(−3.00,2.502,5) as indicated in the literature3. 791 792 Results are similar to those based on the uninformative prior and are reported in the eTable below. 793

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 794 eTable 10B2 - Uninformative prior vs empirical informative prior 795 For uninformative prior: Pain DIC 200.36 - Function DIC 97.4 - Joint Space DIC 114.66 796 Data are standardized mean differences (SMDs) and 95% credibility interval (Crl) Main analysis Sensitivity analysis Outcome Treatment (Uninformative prior) (Empirical informative prior) PAIN Acetaminophen 0.24 (-0.36,0.85) 0.26 (-0.35,0.86) Betamethasone 1.57 (1.25,1.88) 1.56 (1.25,1.88) Calcitonin -0.11 (-0.23,0.01) -0.11 (-0.24,0.03) Celecoxib -0.18 (-0.35,-0.01) -0.18 (-0.35,0.00) Chondroitin Sulfate (CS) -0.06 (-0.17,0.05) -0.06 (-0.18,0.06) Cindunistat -0.04 (-0.15,0.06) -0.04 (-0.15,0.07) Diacerein -0.04 (-0.30,0.22) -0.04 (-0.31,0.23) Diclofenac -0.01 (-0.22,0.20) 0.00 (-0.22,0.22) Etofenamate 0.17 (-0.35,0.69) 0.17 (-0.37,0.70) Etoricoxib -0.10 (-0.35,0.15) -0.09 (-0.36,0.18) Glucosamines -0.11 (-0.26,0.04) -0.11 (-0.26,0.04) Glucosamines + CS -0.13 (-0.29,0.03) -0.12 (-0.29,0.04) Glucosamine Sulfate -0.29 (-0.49,-0.09) -0.29 (-0.50,-0.09) Hyaluronic Acid (HA) -0.06 (-0.18,0.06) -0.06 (-0.19,0.06) HA + Betamethasone -0.41 (-0.90,0.07) -0.40 (-0.90,0.09) HA + Methylprednisolone 0.12 (-0.14,0.38) 0.11 (-0.15,0.38) HA + Triamcinolone -0.50 (-1.14,0.16) -0.51 (-1.16,0.15) Indomethacin 0.04 (-0.15,0.22) 0.03 (-0.17,0.23) Licofelone -0.03 (-0.43,0.36) -0.03 (-0.43,0.38) Methylprednisolone -0.07 (-0.44,0.31) -0.07 (-0.45,0.31) Naproxen -0.08 (-0.39,0.23) -0.07 (-0.39,0.26) Nimesulide -0.07 (-0.44,0.30) -0.06 (-0.45,0.33) Risedronate -0.03 (-0.10,0.03) -0.03 (-0.10,0.04) Rofecoxib 0.11 (-0.12,0.34) 0.12 (-0.12,0.36) Sprifermin 0.52 (0.26,0.78) 0.52 (0.26,0.78) Strontium Ranelate -0.09 (-0.19,0.01) -0.09 (-0.20,0.02) Tiaprofenic Acid -0.05 (-0.21,0.12) -0.05 (-0.23,0.14) Triamcinolone 0.21 (-0.07,0.49) 0.21 (-0.07,0.49) Vitamin E 0.22 (-0.16,0.59) 0.22 (-0.16,0.60) Vitamin D -0.12 (-0.29,0.05) -0.12 (-0.30,0.05) Zoledronic Acid -0.02 (-0.58,0.53) -0.03 (-0.57,0.52) FUNCTION Calcitonin -0.11 (-0.25,0.02) -0.11 (-0.27,0.05) Celecoxib -0.13 (-0.32,0.07) -0.13 (-0.34,0.09) Chondroitin Sulfate -0.03 (-0.20,0.14) -0.03 (-0.21,0.15) Cindunistat -0.03 (-0.13,0.08) -0.03 (-0.15,0.10) Glucosamines -0.04 (-0.20,0.12) -0.04 (-0.21,0.13) Glucosamines + CS -0.02 (-0.19,0.15) -0.02 (-0.20,0.16) Glucosamine Sulfate -0.32 (-0.52,-0.12) -0.32 (-0.53,-0.11) Risedronate -0.02 (-0.08,0.05) -0.02 (-0.09,0.06) Sprifermin 0.32 (0.06,0.58) 0.32 (0.05,0.59) Strontium Ranelate -0.08 (-0.19,0.03) -0.08 (-0.21,0.04) Triamcinolone 0.07 (-0.21,0.35) 0.07 (-0.21,0.36) Vitamin E 0.24 (-0.13,0.62) 0.24 (-0.14,0.63) Vitamin D -0.16 (-0.33,0.02) -0.16 (-0.35,0.02) JSN Calcitonin 0.04 (-0.16,0.24) 0.04 (-0.20,0.29) Celecoxib 0.11 (-0.19,0.41) 0.11 (-0.21,0.43) Chondroitin Sulfate 0.20 (0.07,0.31) 0.19 (0.06,0.32) Cindunistat 0.03 (-0.12,0.18) 0.03 (-0.15,0.21) Diclofenac -0.20 (-0.71,0.31) -0.21 (-0.73,0.32) Doxycycline 0.21 (-0.05,0.48) 0.21 (-0.08,0.51) Glucosamines 0.07 (-0.11,0.26) 0.07 (-0.13,0.27) Glucosamines + CS 0.18 (-0.03,0.39) 0.18 (-0.05,0.40) Glucosamine Sulfate 0.42 (0.19,0.65) 0.42 (0.17,0.67) Hyaluronic Acid 0.26 (-0.42,0.93) 0.04 (-0.24,0.34) MM Inhibitors -0.06 (-0.24,0.13) -0.05 (-0.25,0.14) Risedronate 0.05 (-0.15,0.26) 0.05 (-0.16,0.27) Sprifermin 0.03 (-0.25,0.30) 0.03 (-0.26,0.32) Strontium Ranelate 0.20 (0.05,0.36) 0.20 (0.02,0.38) Triamcinolone 0.01 (-0.50,0.52) 0.01 (-0.52,0.53) Vitamin D 0.11 (-0.11,0.31) 0.09 (-0.15,0.31)

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 534 Primary outcome: 535 536 eFigure 1A - Pain (primary outcome): Network plot - All trials 537

538 539 540 The area of every circle is proportional to the number of randomly assigned patients and indicates the 541 sample size. 542 The width of the lines is proportional to the number of trials that directly compared the two medications (e.g. 543 in this plot the thinnest line corresponds to 1 trial; the thickest line corresponds to 6 trials). 544 545 546

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 547 548 eFigure 1B – Pain (primary outcome): Network plot when trials at high risk of bias 549 were excluded

550 551 The area of every circle is proportional to the number of randomly assigned patients and indicates the 552 sample size. 553 The width of the lines is proportional to the number of trials that directly compared the two medications. 554

555

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 556 eFigure 2 - Pain (primary outcome): Forest plot (estimates as standardized mean 557 difference) - All trials 558 Forest plot for the estimates of long-term treatment effects compared with placebo. Point estimates refer to 559 the posterior mean. The number of trials and the number of patients are reported after each intervention. 560 SMD = standardized mean difference. CrI = credibility interval. IA = Intra-articular. SYSADOA = symptomatic 561 slow acting drug in osteoarthritis.

562 563

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 564 eFigure 3 - Pain (primary outcome): Forest plot (estimates as standardized mean 565 difference) when trials at high risk of bias were excluded 566 Forest plot for the estimates of long-term treatment effects compared with placebo. Point estimates refer to 567 the posterior mean. The number of trials and the number of patients are reported after each intervention. 568 SMD = standardized mean difference. CrI = credibility interval. IA = Intra-articular. SYSADOA = symptomatic 569 slow acting drug in osteoarthritis.

570 571

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 572 573 eFigure 4A - Pain (primary outcome): SUCRA plots when trials at high risk of bias 574 were excluded 575 The Area under the curve (AUC) of cumulative ranking gives the probability for a treatment to be the most 576 effective in reducing pain: the larger is the surface under the curve, the higher will be the probability to reach 577 an higher rank.

578

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 579 580 581 eFigure 4A - Pain (primary outcome): SUCRA plots when trials at high risk of bias 582 were excluded (continued)

583 584

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 585 eFigure 4B - Pain (primary outcome): rankogram plots when trials at high risk of 586 bias were excluded 587 Ranking of treatments for reducing pain symptoms. The vertical axis gives the probability for the specific 588 treatment to take each of the ranks of the horizontal axis, where 0 is the best and 32 is the worst.

589

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 590 eFigure 4B - Pain (primary outcome): rankogram plots when trials at high risk of 591 bias were excluded (continued)

592 593

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 594 eFigure 4C - Pain (primary outcome): ranking forest plot when trials at high risk of 595 bias were excluded 596 Forest plot of posterior rankings for intervention (mean rank, 2.5 and 97.5 percentiles) 597

598 599 600

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 601 602 603 eFigure 5 - Pain (primary outcome): SUCRA forest plot – All trials 604

605 606

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 607 eFigure 5A - Pain (primary outcome): SUCRA plots – All trials 608 The Area under the curve (AUC) of cumulative ranking gives the probability for a treatment to be the most 609 effective in reducing pain: the larger is the surface under the curve, the higher will be the probability to reach 610 an higher rank.

611 612

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 613 eFigure 5A - Pain (primary outcome): SUCRA plots – All trials (continued)

614 615

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 616 eFigure 5B - Pain (primary outcome): rankogram plots – All trials 617 Ranking of treatments for reducing pain symptoms. The vertical axis gives the probability for the specific 618 treatment to take each of the ranks of the horizontal axis, where 0 is the best and 32 is the worst.

619 620

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 621 eFigure 5B - Pain (primary outcome): rankogram plots – All trials (continued)

622 623

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 624 eFigure 5C - Pain (primary outcome): ranking forest plot – All trials 625 Forest plot of posterior rankings for intervention (mean rank, 2.5 and 97.5 percentiles)

Intervention Mean (2.5,97.5 perc.)

Glucosamine Sulfate 4,12 (1,13) HA + Betamethasone 4,33 (1,24) HA + Triamcinolone 4,33 (1,26) Celecoxib 7,13 (2,17) Glucosamines + CS 10,4 (3,22) Vitamin D 10,91 (3,24) Calcitonin 11,32 (4,22) Glucosamines 11,37 (4,23) Etoricoxib 12,15 (3,24) Strontium Ranelate 12,36 (5,22) Naproxen 13,67 (3,26) Nimesulide 14,4 (2,28) Hyaluronic Acid (HA) 14,51 (6,24) Chondroitin Sulfate (CS) 14,69 (7,24) Methylprednisolone 14,73 (2,29) Tiaprofenic Acid 15,83 (4,26) Cindunistat 16,09 (7,25) Licofelone 16,24 (2,29) Diacerein 16,32 (3,28) Zoledronic Acid 16,62 (1,31) Risedronate 17,19 (9,24) Diclofenac 18,33 (8,26) Placebo 20,04 (14,25) Indomethacin 20,86 (7,28) Etofenamate 22,99 (3,31) HA + Methylprednisolone 23,71 (9,30) Rofecoxib 24,44 (13,29) Acetaminophen 24,53 (3,31) Vitamin E 25,62 (8,31) Triamcinolone 26,36 (14,30) Sprifermin 30,43 (28,31) Betamethasone 32 (32,32)

0 5 10 15 20 25 30 35 40 626 Ranking 627

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 639 Secondary outcomes: 640

641 eFigure 6 - Network plot for comparisons on the secondary outcome physical 642 function 643

644 645 The area of every circle is proportional to the number of randomly assigned patients and indicates the 646 sample size. 647 The width of the lines is proportional to the number of trials that directly compared the two medications. 648 649

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 650 651 eFigure 7 - Physical Function (secondary outcome): Forest plot 652 Forest plot for the estimates of long-term treatment effects compared with placebo. Estimates are expressed 653 as standardized mean difference (SMD). Point estimates refer to the posterior mean. The number of trials 654 and the number of patients are reported after each intervention. CrI = credibility interval. IA = Intra-articular. 655 SYSADOA = symptomatic slow acting drug in osteoarthritis. 656

657

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 658 eFigure 8 - Physical function (secondary outcome): SUCRA forest plot 659

Intervention [trials] Mean (95% CrI)

Glucosamine Sulfate [2] 0.97 (0.77,1.00)

Vitamin D [2] 0.80 (0.31,1.00)

Celecoxib [2] 0.74 (0.23,1.00)

Calcitonin [1] 0.72 (0.23,0.92)

Strontium Ranelate [1] 0.65 (0.23,0.92)

Glucosamines [3] 0.50 (0.15,0.92)

Chondroitin Sulfate (CS) [3] 0.47 (0.15,0.85)

Cindunistat [1] 0.47 (0.15,0.85)

Glucosamines + CS [2] 0.45 (0.08,0.85)

Risedronate [3] 0.43 (0.15,0.77)

Placebo [16] 0.35 (0.15,0.62)

Triamcinolone [2] 0.29 (0.00,0.92)

Vitamin E [1] 0.12 (0.00,0.77)

Sprifermin [1] 0.04 (0.00,0.15)

0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 660 SUCRA - Surface Under the Cumulative RAnking Curve 661 662

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 663 eFigure 8A - Physical function (secondary outcome): SUCRA plots 664 The Area under the curve (AUC) of cumulative ranking gives the probability for a treatment to be the most 665 effective in reducing pain: the larger is the surface under the curve, the higher will be the probability to reach 666 an higher rank.

667

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 668 eFigure 8B - Physical function (secondary outcome): rankogram plots 669 Ranking of treatments for improving physical function. The vertical axis gives the probability for the specific 670 treatment to take each of the ranks of the horizontal axis, where 0 is the best and 14 is the worst.

671 672

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 673 eFigure 8C - Physical function (secondary outcome): ranking forest plot 674 Forest plot of posterior rankings for intervention (mean rank, 2.5 and 97.5 percentiles)

Intervention Mean (2.5,97.5 perc.)

Glucosamine Sulfate 1,36 (1,4)

Vitamin D 3,63 (1,10)

Celecoxib 4,42 (1,11)

Calcitonin 4,58 (2,10)

Strontium Ranelate 5,6 (2,11)

Glucosamines 7,52 (2,12)

Chondroitin Sulfate (CS) 7,85 (3,12)

Cindunistat 7,91 (3,12)

Glucosamines + CS 8,17 (3,13)

Risedronate 8,44 (4,12)

Placebo 9,42 (6,12) Triamcinolone 10,26 (2,14) Vitamin E 12,38 (4,14) Sprifermin 13,46 (12,14)

0 3 6 9 12 15 18 675 Ranking 676 677

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 694 eFigure 9 - Network plot for comparisons on the secondary outcome joint space 695 narrowing 696

697 698 The area of every circle is proportional to the number of randomly assigned patients and indicates the 699 sample size. 700 The width of the lines is proportional to the number of trials that directly compared the two medications. 701 702 703

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 704 705 eFigure 10 - Joint space narrowing (secondary outcome): Forest plot 706 Forest plot for the estimates of long-term treatment effects compared with placebo. Estimates are expressed 707 as standardized mean difference (SMD). Point estimates refer to the posterior mean. The number of trials 708 and the number of patients are reported after each intervention. CrI = credibility interval. IA = Intra-articular. 709 SYSADOA = symptomatic slow acting drug in osteoarthritis. 710 The “Favors active treatment/Favors placebo” orientation has been flipped compared with the original 711 analysis, to be consistent with the other Forest plots in the manuscript. 712

713

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 724 eFigure 11 - Joint space narrowing (secondary outcome): SUCRA forest plot 725

Intervention [trials] Mean (95% CrI)

Glucosamine Sulfate [2] 0.95 (0.75,1.00)

Chondroitin Sulfate (CS) [6] 0.73 (0.44,0.94)

Strontium Ranelate [1] 0.73 (0.38,0.94)

Doxycycline [1] 0.72 (0.19,1.00)

Glucosamines + CS [2] 0.68 (0.25,0.94)

Hyaluronic Acid [2] 0.66 (0.00,1.00)

Celecoxib [1] 0.53 (0.06,0.94)

Vitamin D [2] 0.53 (0.06,0.94)

Glucosamines [3] 0.45 (0.06,0.81)

Risedronate [2] 0.41 (0.06,0.88)

Calcitonin [1] 0.39 (0.06,0.81)

Triamcinolone [1] 0.38 (0.00,1.00)

Sprifermin [1] 0.37 (0.00,0.88)

Cindunistat [1] 0.35 (0.06,0.75)

Placebo [22] 0.27 (0.06,0.50)

MMP Inhibitors [1] 0.20 (0.00,0.62)

Diclofenac [1] 0.15 (0.00,0.88)

0 0,2 0,4 0,6 0,8 1 1,2 1,4 726 SUCRA - Surface Under the Cumulative RAnking Curve 727 728

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 729 eFigure 11A - Joint space narrowing (secondary outcome): SUCRA plots 730 The Area under the curve (Auc) of cumulative ranking gives the probability for a treatment to be the most 731 effective in reducing pain: the larger is the surface under the curve, the higher will be the probability to reach 732 an higher rank.

733

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 734 eFigure 11B - Joint space narrowing (secondary outcome): rankogram plots 735 Ranking of treatments for improving physical function. The vertical axis gives the probability for the specific 736 treatment to take each of the ranks of the horizontal axis, where 0 is the best and 17 is the worst.

737 738

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021 739 eFigure 11C - Joint space narrowing (secondary outcome): ranking forest plot 740 Forest plot of posterior rankings for intervention (mean rank, 2.5 and 97.5 percentiles) 741

Intervention Mean (2.5,97.5 perc.)

Glucosamine Sulfate 1,5 (1,5)

Strontium Ranelate 4,85 (2,10)

Chondroitin Sulfate (CS) 4,87 (2,9)

Doxycycline 5,12 (1,14)

Glucosamines + CS 5,7 (1,13)

Celecoxib 8,28 (1,16)

Vitamin D 8,53 (2,16)

Glucosamines 9,57 (3,16) Risedronate 10,24 (3,16) Calcitonin 10,51 (3,16) Hyaluronic Acid (HA) 10,52 (2,17) Triamcinolone 10,74 (1,17) Sprifermin 10,76 (2,17) Cindunistat 11,11 (5,16) Placebo 12,51 (9,15) Matrix Metalloproteinase Inhibit 13,66 (7,17) Diclofenac 14,52 (2,17)

0 5 10 15 20 25 742 Ranking 743 744

Downloaded From: https://edhub.ama-assn.org/ on 10/04/2021