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Online supplement to Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute Gout: A Systematic Review of Randomized Controlled Trials, The Journal of Rheumatology (doi:10.3899/jrheum.170137)

ONLINE SUPPLEMENTARY MATERIAL

Appendix A. Search terms.

Medline

exp Gout/ 1 2 gout*.tw. 3 (uric adj10 arthritis).tw. 4 toph*.tw. 5 or/1-4 6 exp Steroids/ 7 exp Adrenal Cortex Hormones/ 8 steroid*.tw. 9 glucocorticoid*.tw. 10 corticosteroid*.tw. (betamethasone or desoximetasone or dexamethasone or methylprednisolone or 11 paramethasone or prednisolone or prednisone or triamcinolone or cortisone or cortisol or hydrocortisone).tw. 12 or/6-11 13 exp Anti-Inflammatory Agents, Non-Steroidal/ 14 ((nonsteroid* or non-steroid*) adj (antiinflammator* or anti-inflammator*).tw. 15 nsaid*.tw. 16 ((cyclooxygenase or cox) adj10 inhibitor*).tw. (aspirin or celecoxib or diclofenac or etanercept or etodolac or etoricoxib or flubiprofen or ibuprofen or indomethacin or ketoprofen or ketorolac or meclofenamic or mefenamic 17 or meloxicam or naproxen or niflumic or oxyphenbutazone or phenylbutazone or piroxicam or rofecoxib or salicylates or sulindac or suprofen or tolmetin).tw. 18 or/13-17 19 randomized controlled trial.pt. 20 controlled clinical trial.pt. 21 pragmatic clinical trial.pt. 22 randomized.ab. 23 placebo.ab. 24 drug therapy.fs. 25 randomly.ab. 26 trial.ab. 27 groups.ab. 28 or/19-27 29 animals/ not (humans/ and animals/) 30 28 not 29 31 and/5,12,18,30

EMBASE

Gout/ 1 2 gout*.tw. 3 (uric adj10 arthritis).tw. 4 toph*.tw. 5 or/1-4 6 exp Steroid/ 7 Corticotropin/ 8 steroid*.tw. 9 glucocorticoid*.tw. 10 corticosteroid*.tw. 11 corticotropin*.tw. (betamethasone or desoximetasone or dexamethasone or methylprednisolone or 12 paramethasone or prednisolone or prednisone or triamcinolone or cortisone or cortisol or hydrocortisone).tw. 13 or/6-12 14 exp nonsteroid antiinflammatory agent/ 15 ((nonsteroid* or non-steroid*) adj (antiinflammator* or anti-inflammator*)).tw. 16 nsaid*.tw. 17 exp cyclooxygenase 2 inhibitor/ 18 ((cyclooxygenase or cox) adj10 inhibitor*).tw. (aspirin or celecoxib or diclofenac or etanercept or etodolac or etoricoxib or flubiprofen or ibuprofen or indomethacin or ketoprofen or ketorolac or meclofenamic or mefenamic or 19 meloxicam or naproxen or niflumic or oxyphenbutazone or phenylbutazone or piroxicam or rofecoxib or salicylates or sulindac or suprofen or tolmetin).tw. 20 or/14-19 21 randomized controlled trial/ 22 crossover procedure/ 23 double-blind procedure/ 24 single-blind procedure/ 25 random$.tw. 26 factorial$.tw. 27 (crossover$ or cross-over$).tw. 28 placebo$.tw. 29 (double$ adj blind$).tw. 30 (singl$ adj blind$).tw. 31 assign$.tw. 32 allocat$.tw. 33 or/21-32 34 and/5,13,20,33 2

CENTRAL

#1 gout*:ti,ab,kw #2 (uric near/10 arthritis):ti,ab,kw #3 toph*:ti,ab,kw #4 {or #1-#3}c #5 MeSH descriptor: [Steroids] explode all trees #6 MeSH descriptor: [Adrenal Cortex Hormones] explode all trees #7 MeSH descriptor: [Adrenocorticotropic Hormone] explode all trees #8 corticotropin*:ti,ab,kw #9 steroid*:ti,ab,kw #10 glucocorticoid*:ti,ab,kw #11 corticosteroid*:ti,ab,kw #12 (betamethasone or desoximetasone or dexamethasone or methylprednisolone or paramethasone or prednisolone or prednisone or triamcinolone or cortisone or cortisol or hydrocortisone):ti,ab,kw #13 {or #5-#12}s #14 MeSH descriptor: [Anti-Inflammatory Agents, Non-Steroidal] explode all trees #15 ((nonsteroid* or non-steroid*) next (antiinflammator* or anti-inflammator*)):ti,ab,kw #16 nsaid*:ti,ab,kw #17 ((cyclooxygenase or cox) near/10 inhibitor*):ti,ab,kw #18 (aspirin or celecoxib or diclofenac or etanercept or etodolac or etoricoxib or flubiprofen or ibuprofen or indomethacin or ketoprofen or ketorolac or meclofenamic or mefenamic or meloxicam or naproxen or niflumic or oxyphenbutazone or phenylbutazone or piroxicam or rofecoxib or salicylates or sulindac or suprofen or tolmetin):ti,ab,kw #19 {or #14-#18}

ISRCTN Registry

Website: http://www.isrctn.com Use advanced search and enter “gout” in the condition column

WHO ICTRP Registry

Website: http://apps.who.int/trialsearch/ Used search terms “gout” and “gouty”

ClinicalTrials.gov Website: https://clinicaltrials.gov/

Used search terms “gout” and “gouty”

Supplementary Table 1. Definitions of the clinical efficacy and safety outcomes.

Measurement Outcomes Outcomes Definition Scale Definition Study Tools / Units

Pain The degree of pain of the affected joints during activity, measured as mean VAS 0 to 10 cm 0=absence of pain; 10=the most severe pain ever Man 2007(27)

changes on any scale experienced

VAS 0 to 100 mm 0=absence of pain; 100=the most severe pain ever Rainer 2016(19)

The degree of pain of the affected joints, measured as mean changes on any experienced Janssens 2008(26)

scale 5-point Likert scale 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme Xu 2016(18)

Zhang 2014(17)

Swelling Swelling of affected joints, measured as mean changes on any scale 4-point Likert scale 0=no swelling, 1=palpable, 2=visible, 3=bulging Xu 2016(18)

beyond the joint margins Zhang 2014(17)

Erythema Redness of affected joints, measured as mean changes on any scale 3-point Likert scale 0=absent, 1=not assessable, 2=present Xu 2016(18)

Rainer 2016(19)

Tenderness Tenderness on palpation or passive movement of affected joints, measured as 3-point Likert scale 0=no pain, =patient states 'there is pain, 2=patient Xu 2016(18)

mean changes on any scale states 'there is pain' and withdraws his affected limbs

4-point Likert scale 0=no pain, 1=patient states 'there is pain, 2=patient Zhang 2014(17)

states 'there is pain' and winces, 3=patient states

'there is pain' and winces and withdraws his affected

limbs

5-point Likert scale N/A Rainer 2016(19)

Activity General disability or restriction to joint activity, measured as mean changes on VAS 0 to 100 mm 0=means absence of disability to 100=completely Janssens 2008(26)

limitation any scale unable to do something

4-point Likert scale 0=no restriction, 1=moderately restricted, Xu 2016(18)

2=significantly restricted, 3=cannot take care of

themselves

Response to Any clinical improvement from baseline, evaluated by physicians, measured as 5-point Likert scale 0=very good, 1=good, 2=fair, 3=poor, 4=very poor Xu 2016(18)

therapy mean changes or proportions between considerable improvement (i.e. good Zhang 2014(17)

response or improvement > 50%) and slight or no improvement on any scale 5-point scale 0=total resolution, 2=improvement > 50%, Alloway 1993(25)

2=improvement < 50%, 3=no change, 4=worsening

of symptoms or involvement of previously uninvolved

joints

Quality of life Quality of life, measured as changes in mean score of any standard validated SF-36 Rainer 2016(19)

quality of life scale

Time to Time to resolution, measured in days / months / other units Days Alloway 1993(25)

resolution

Number of Number or doses of additional analgesics administered, besides assigned Number of tablets Rainer 2016(19)

supplementary intervention, to reduce pain Man 2007(27)

analgesics

Adverse events Any bleeding (minor and major bleeding, including gastrointestinal and Number of events Xu 2016(18)

intracranial bleeding), gastric or abdominal pain indigestion, diarrhea, Zhang 2014(17)

flatulence, nausea, vomiting, headache, dizziness, itchiness, fatigue or Rainer 2016(19)

drowsiness, insomnia or sleep disorder, dry mouth, skin rash, edema, Janssens 2008(26)

hyperglycemia, cardiovascular adverse events (shortness of breath, chest Man 2007(27)

pain, and palpitations), serious adverse events requiring hospitalization, total Alloway 1993(25)

adverse events, discontinuation or withdrawal to treatment due to adverse

events, and recurrent gout attack within follow up period

VAS, Visual Analogue Scale; SF-36, 36-item Short Form Survey

Supplementary Figure 1. Risks of bias in the included trials.