Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: McInnes IB, Behrens F, Mease PJ, et al. Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial. Lancet 2020; 395: 1496–505.

APPENDIX

Secukinumab versus Adalimumab Comparison for the Treatment of Active Psoriatic Arthritis (EXCEED): A Randomised, Double-blind, Active-controlled Phase 3b Trial Iain B McInnes1*, Frank Behrens2, Philip J Mease3, Arthur Kavanaugh4, Christopher Ritchlin5, Peter Nash6, Jordi Gratacós Masmitja7, Philippe Goupille8, Tatiana Korotaeva9, Alice B Gottlieb10, Ruvie Martin11, Kevin Ding12, Pascale Pellet13, Shephard Mpofu14, and Luminita Pricop15 on behalf of EXCEED Study 1University of Glasgow, Glasgow, 2Rheumatology University Hospital and Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP and Fraunhofer Cluster of Excellence for Immune- Mediated Diseases CIMD, Goethe University, Frankfurt, Germany 3Swedish Medical Centre/Providence St. Joseph Health and University of Washington, Seattle, United States 4Rheumatology, Allergy, Immunology Division, University of California, San Diego, School of Medicine, La Jolla, United States, La Jolla, United States 5Allergy/Immunology and Rheumatology Division, University of Rochester, Rochester, United States 6Department of Medicine, Griffith University, Brisbane, Australia 7Rheumatology Department, University Hospital Parc Taulí, Sabadell, UAB, 8Department of Rheumatology and INSERM-CIC1415, University hospital of Tours, EA 7501 GICC, University of Tours, Tours, France 9Research Institute of Rheumatology n.a. V.A. Nasonova, , 10Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, United States 11Novartis Pharmaceuticals Corporation, East , United States 12Novartis Pharmaceuticals Corporation, East Hanover, United States 13Novartis Pharma AG, , Switzerland 14Novartis Pharma AG, Basel, Switzerland 15Novartis Pharmaceuticals Corporation, East Hanover, United States

Corresponding author: Dr. (Prof.) Iain B McInnes Director Institute of Infection, Immunity and Inflammation College of Medical, Veterinary and Life Sciences University of Glasgow Scotland, United Kingdom Tel: + +44 141 330 8412 E-mail: [email protected]

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1. List of Investigators

Investigator and Position / Role Facility Name Country No. of other important Address Patients participants Country Enrolled Dr. Jane Zochling Principal Southern Clinical Research Pty Ltd Australia 12 Investigator Hobart, TAS, Australia, 7000 Dr. Peter Nash Principal Rheumatology Research Unit Sunshine Australia 8 Investigator Coast Maroochydore, QLD, Australia, 4558 Dr. Paul Bird Principal Optimus Clinical Research Australia 3 Investigator Kogarah, NSW, Australia, 2217 Prof Andrew Ostor Principal Emeritus Research Australia 10 Investigator Camberwell, VIC, Australia, 3145 Dr. Elke Boettcher Principal Ordination Dr Omid Zamani Austria 0 Investigator Austria Assoc. Prof Principal UMHAT Dr George Stranski Bulgaria 5 Nikolay Georgiev Investigator Pleven, Nikolov Bulgaria, 5800 Dr. Boycho Principal Military Medical Academy Bulgaria 4 Oparanov Investigator Sofia, Bulgaria, Bulgaria, 1606 Prof. Rumen Principal UMHAT Sveti Ivan Rilski EAD Bulgaria 3 Stoilov Investigator Sofia, Bulgaria, 1612 Dr. Ivan Goranov Principal MHAT Plovdiv AD Bulgaria 8 Investigator Plovdiv, Bulgaria, 4002 Prof. Anastas Principal UMHAT Kaspela Bulgaria 7 Batalov Investigator Plovdiv, Bulgaria, 4002 Prof. Rasho Principal UMHAT Sveti Ivan Rilski EAD Bulgaria 1 Rashkov Investigator Sofia, Bulgaria, 1612 Dr. Timothy Principal Manitoba Clinic Canada 4 McCarthy Investigator Winnipeg, MB, Canada, R3A 1M1 Dr Frederic Morin Principal Centre de Recherche Musculo- Canada 8 Investigator Squelettique Trois-Rivieres, QC, Canada, G8Z 1Y2 Dr Milton Baker Principal PerCuro Clinical Research Ltd Canada 3 Investigator Victoria, BC, Canada, V8V 3M9 Dr. Eva Principal Medical Plus s.r. o. Czech Republic 26 Dokoupilova Investigator Uherske Hradiste, Czech Republic, 686 01 Dr. Dagmar Principal Revmatologie Bruntal s.r. o. Czech Republic 11 Galatikova Investigator Bruntal, Czech Republic, 792 01

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Dr. Rudolf Horvath Principal FN Motol Czech Republic 15 Investigator Praha 5, Czech Republic, 150 06 MD Herman F Principal Revmatologicky ustav Czech Republic 22 Mann Investigator Praha 2, Czech Republic, 128 50 Dr Petr Vitek Principal PV MEDICAL s r o Czech Republic 6 Investigator Zlin, Czech Republic, 760 01 Dr. Lars Erik Principal HS Frederiksberg Hospital, Parker Denmark 17 Kristensen Investigator institute Frederiksberg, Denmark, DK-2000 Dr. Triin Savi Principal East Central Hospital Estonia 6 Investigator Magdalena Policlinic Tallinn, Estonia, 11312 Dr. Mart Kull Principal Meditrials OU Estonia 21 Investigator Tartu, Estonia, 50406 Dr. Ene Ojassalu Principal North Estonia Medical Centre Estonia 13 Investigator Foundation Tallinn, Estonia, 13419 Dr. Pentti Jarvinen Principal Kiljavan laaketutkimus Finland 0 Investigator Hyvinkaa, Finland, 05800 MD. Aulikki Principal Pihlajalinna Ite Kuopio Finland 0 Kononoff Investigator Kuopio, Finland, 70100 Pr Philippe Principal CHRU - Hospital Trousseau France 0 Goupille Investigator Chambray les Tours, France, 37170 Dr. Gregoire Principal Centre Hospitalier Dubois France 0 Lambert De Cursay Investigator Brive-la-Gaillarde, France, 19100 Dr. Emmanuelle Principal Centre Hospitalier du Mans France 0 Dernis Investigator Le Mans, France, 72037 Dr. Slim Lassoued Principal Centre Hospitalier Jean Rougie France 0 Investigator Cahors, France, 46000 Dr. Martin Principal CHU Gabriel Montpied France 0 Soubrier Investigator Clermont Ferrand, France, 63000 Dr. Elisabeth Solau Principal CHU Hospital Jean Bernard France 0 Gervais Investigator Poitiers, France, 86000 Dr Eric Principal CHR ORLEANS France 0 Lespessailles Investigator Orleans, France, 45067 Dr. Pascal Richette Principal Centre hospitalier Lariboisiere France 0 Investigator , France, 75010

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Prof. Dr. med. Principal Rheumazentrum Ruhrgebiet St Josefs Germany 1 Juergen Braun Investigator Krankenhaus Herne, Germany, 44649 Dr. med. Jan Principal Rheumatologische Schwerpunktpraxis Germany 10 Brandt Juergens Investigator Dr Jan Brandt-Juergens , Germany, 12161 Prof. Dr. med. Principal Universitaetsmedizin Charite Germany 2 Gerd Ruediger Investigator Berlin, Burmester Germany, 10117 Dr. med. Georg P. Principal Praxis fur Klinische Studien Dr. med. Germany 9 Dahmen Investigator Georg Dahmen , Germany, 22415 Mr. Andrei Principal Klinische Forschung Berlin Mitte Germany 2 Khariouzov Investigator GmbH Berlin, Germany, 10117 Prof. Dr. med. Principal Institut fuer Praeventive Medizin & Germany 3 Ruediger Moericke Investigator Klinische Forschung GbR , Germany, 39110 Prof. Dr. med. Principal Rheumazentrum Bad Doberan Germany 3 Gunther Neeck Investigator Bad Doberan, Germany, 18209 Prof. Dr. med. Principal Universitaetsmedizin Charite, Campus Germany 1 Denis Poddubnyy Investigator Mitte, Med. Klinik I Berlin, Germany, 12200 Dr. med. Florian Principal Rheumatologische Schwerpunktpraxis Germany 9 Schuch Investigator Erlangen Erlangen, Germany, 91056 Ms. Charlotte von Principal Klinische Forschung gGmbH Germany 6 Engelhardt Investigator Schwerin, Germany, 19055 Prof. Dr. med. Principal St. Josef Hospital,Hauttumorzentrum, Germany 7 Thilo Gambichler Investigator Ruhr- Universität Bochum Bochum, Germany, 44791 Dr. med. Georg Principal Rheumapraxis an der Hase Germany 1 Gauler Investigator Osnabruck, Germany, 49074 Dr. med. Rieke Principal Schlosspark Klinik, Innere Medizin II, Germany 2 Alten Investigator Rheumatologie Berlin, Germany, 14059 Prof. Dr. med. Ulf Principal Universitaetsklinikum Leipzig AoR, Germany 9 Wagner Investigator Klinik für Gastroenterologie Leipzig, Germany, 04103 Prof. Dimitrios Principal University General Hospital ATTIKON Greece 0 Boumpas Investigator Chaidari , Greece, Greece, 12462

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Prof Dr Dimitrios Principal General Hospital of Athens Ippokrateio Greece 0 Vassilopoulos Investigator Athens, Greece, Greece, 11527 Prof. Petros Principal General Hospital of Athens Laiko Greece 0 Sfikakis Investigator Athens, Greece, Greece, 115 27 Prof. Athanasios G Principal General Hospital of Athens Laiko Greece 0 Tzioufas Investigator Athens, Greece, Greece, 115 27 Dr. Alexandros Principal General Hospital of Thessaloniki Greece 0 Garyfallos Investigator IPPOKRATEIO Thessaloniki, Greece, Greece, 54642 Dr. Regina Cseuz Principal Revita Reumatologiai Rendelő Hungary 1 Investigator , Hungary, 1027 Dr. Edit Drescher Principal Vital Medical Center Hungary 3 Investigator Veszprem, Hungary, 8200 Dr. Marta Kiraly Principal Petz Aladár Megyei Oktató Kórház Hungary 3 Investigator Reumatológiai Osztály Győr, Hungary, Hungary, 9025 Dr. Sandor Szanto Principal Debreceni Egyetem Klinikai Központ Hungary 5 Investigator Belgyógyászati Klinika, Re Debrecen, Hungary, 4032 Dr Edit Toth Principal Pest Megyei Flór Ferenc Kórház, Hungary 4 Investigator Reumatológiai és Fizioterá Kistarcsa, Hungary, 2143 Dr. Ilona Ujfalussy Principal Magyar Honvédség Egészségügyi Hungary 4 Investigator Központ, Reumatológiai Oszt Budapest, -, Hungary, 1062 Dr. Peter Balint Principal Orszagos Reumatologiai es Hungary 2 Investigator Fizioterapias Intezet Budapest, Hungary, 1023 Dr. Gerdur Principal Landspitali Haskolasjukrahus Iceland 0 Grondal Investigator Fossvogur Reykjavik, Iceland, 108 Dr. Jyotsna Oak Principal Kokilaben Dhirubhai Ambani Hospital India 0 Investigator nd Medical Research Inst Mumbai, Maharashtra, India, 400 053 Dr. Praveen Jadhav Principal Sujata Birla Hospital and Medical India 20 Investigator Research Center Nashik, Maharashtra, India, 422 101 Dr. Sarath Chandra Principal Krishna Institute of Medical Sciences India 4 Mouli Veeravali Investigator Ltd Secunderabad, Telangana, India, 500003

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Prof Uma Kumar Principal All India Institute of Medical Science India 0 Investigator New Delhi, New Delhi, India, 110029 Prof. Merav Lidar Principal The Chaim Sheba Medical Center Israel 0 Investigator Ramat Gan, Israel, 5266202 Prof. Itzhak Rosner Principal Bnai Zion Medical Center Israel 0 Investigator Haifa, Israel, 3339419 Prof Yair Molad Principal Rabin Medical Center Israel 0 Investigator Petach Tikva, Israel, 49100 Prof. Ori Elkayam Principal Tel Aviv Sourasky Medical Center Israel 0 Investigator Ichilov Tel Aviv, Israel, 64239 Prof Yair Levy Principal Meir Sapir Medical Center Israel 0 Investigator Kfar Saba, Israel, 4428164 Prof. Alexandra Principal Rambam Medical Center Israel 0 Balbir Gurman Investigator Haifa, Israel, 3525408 Dr Devy Zisman Principal Carmel Medical Center Israel 0 Investigator Haifa, Israel, 34362 Dr. Carlo Selmi Principal IRCCS Istituto Clinico Humanitas 3 Investigator ROZZANO, ITALY, Italy Dr. Luca Idolazzi Principal Ospedale Borgo Italy 13 Investigator Verona, VR, Italy, 37126 Elisa Rossi Principal Azienda Osp.-Univ. Bologna - Italy 11 Investigator Policlinico S.Orsola-Malpighi Bologna, Italy, Italy, 40138 Dr. Marta Mosca Principal Azienda Ospedaliero-Universitaria Italy 3 Investigator Pisana "Santa Chiara" Pisa, Italy, 56126 Dr. Elena Marina Principal Ospedale San Raffaele IRCCS S R L Italy 2 Baldissera Investigator Milano, MI, Italy, 20132 Dr. Enrico Fusaro Principal AOU Citta della Salute e della Scienza Italy 2 Investigator di Torino Torino, Italy, 10126 Dr. Gerolamo Principal Stab Osp La Colletta Presidio Ospedal Italy 2 Bianchi Investigator Unico ASL 3 Genovese Arenzano, GE, Italy, 16011 Dr. Ju Ha Lee Principal Seoul St Marys Hospital Korea, Republic of 2 Investigator Seoul, Seocho gu, Korea, Republic of, 06591

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Prof. Sang heon Principal Konkuk University Medical Center Korea, Republic of 0 Lee Investigator Seoul, Seoul, Korea, Republic of, 05030 Dr. Sarmite Principal Dr Saleniece private practice in Latvia 0 Saleniece Investigator rheumatology Valmiera, Latvia, LV-4201 Dr. Anna Principal ORTO Clinic Latvia 0 Mihailova Investigator , Latvia, LV-1005 Dr Asta Principal HoLUoHS Kaunas Clinics Lithuania 12 Baranauskaite Investigator Kaunas, Lithuania, LT-50161 Ms Loreta Principal Klaipeda University Hospital Lithuania 15 Bukauskiene Investigator Klaipeda, Lithuania, Lithuania, LT-92288 Dr. Rasa Kausiene Principal Republican Siauliai Hospital Lithuania 12 Investigator Siauliai, Lithuania, LT-76231 Dr Harald E Principal Medische Spectrum Twente Netherlands 0 Vonkeman Investigator Enschede, Netherlands, 7512KZ Dr. EN Griep Principal Antonius Ziekenhuis Sneek Netherlands 0 Investigator Sneek, Netherlands, 8601 ZK Dr. Elzbieta Gigiel Principal NSZOZ Unica CR Poland 13 Investigator Dopiewo, Poland, 62 069 Dr Marzena Principal Narodowy Instytut Geriatrii Poland 6 Olesinska Investigator Reumatologii i Rehabilitacji Warszawa, Poland, Poland, 02-637 Dr. Brygida Principal Narodowy Instytut Geriatrii Poland 8 Kwiatkowska Investigator Reumatologii i Rehabilitacji Warszawa, Poland, Poland, 02-637 Prof Dr Marek Principal SP Szpital Kliniczny nr 1 im, prof Poland 3 Brzosko Investigator Tadeusza Soko¿owskiego PU Szczecin, Poland, 71-252 Prof. Witold Principal Wojskowy Instutyt Medyczny CSK Poland 5 Owczarek Investigator MON Warszawa, Poland, 04 141 Dra. Elsa Sousa Principal Centro Hospitalar Lisboa Norte Portugal 3 Investigator Lisboa, Portugal, 1649-035 Dra. Alexandra Principal Centro Hospitalar de Sao Joao Portugal 1 Bernardo Investigator Porto, Portugal, Portugal, 4200 319 Dr. Antonio Principal CHP Hospital Geral de Santo Antonio Portugal 2 Marinho Investigator Porto, Portugal, 4099 001 Dr Jose Costa Principal Unidade Local de Saude do Alto Douro Portugal 4 Investigator e Minho ULSAM

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Ponte de Lima, Portugal, 4990 041 Prof. Natalia Principal Baranovs Republican Hospital Russia 7 Nikolaevna Investigator Petrozavodsk, Vezikova Russia, 185019 Dr. Irina Andreeva Principal Smolensk State Medical Academy of Russia 12 Investigator Roszdrav Smolensk, Russia, 214019 Dr. Galina Principal Nizhny Novgorod City hospital no 13 of Russia 15 Vasilievna Investigator Avtozavodsky region Shestakova Nizhny Novgorod, Russia, 603018 Prof. Tatiana Principal Kemerovo State Medical Academy Russia 12 Alekseevna Investigator Kemerovo, Raskina Russia, 650000 Prof. Nadezda Principal Ural State Medical University Russia 10 Vladimirovna Investigator Ekaterinburg, Izmozherova Russia, 620149 Dr. Svetlana Principal Medical Center Maximum zdorovia Russia 6 Polyakova Investigator Kemerovo, Russia, 650066 Dr. Olga Borisovna Principal Clinical Hospital for Emergency Russia 9 Ershova Investigator Medical Care na N V Solovy Yaroslavl, Russia, 150003 Dr. Evgenia Principal City clinical hospital 1 n a N I Pirogov Russia 5 Isaakovna Shmidt Investigator Moscow, Russia, 119049 Dr Tatiana Principal Institute of Rheumatology of Russian Russia 11 Korotaeva Investigator Academy Moscow, Russia, 115522 Prof. Alexander Principal Rostov on Don State Med University Russia 12 Alexianosovich Investigator Rostov on Don, Kastanayan Russia, 344022 Dr. Maria Principal ARTROMAC no Slovakia (Slovak 9 Oetterova Investigator Kosice, Slovakia, Republic) Slovakia (Slovak Republic), 04011 Dr. Livia Bruskova Principal Reumacentrum s r o Slovakia (Slovak 6 Investigator Partizanske, Slovakia, Republic) Slovakia (Slovak Republic), 95801 Dr. Eva Ladicka Principal LERAM s.r.o., Reumatologicka Slovakia (Slovak 7 Investigator ambulancia Republic) Topolcany, Slovakia, Slovakia (Slovak Republic), 95501 Dr. Emoke Stenova Principal I.interná klinika Slovakia (Slovak 4 Investigator , Slovakia, Republic) Slovakia (Slovak Republic), 81369 Dr. Alberto Alonso Principal Hospital de Cruces Spain 7 Investigator Baracaldo, Bizkaia, Spain, 48903 Dr. Jordi Gratacos Principal Corporacio Sanitaria Parc Tauli Spain 0 Investigator Sabadell

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Sabadell, , Spain, 08208 Dr. Juan de Dios Principal Hospital Clinic l Provincial De Spain 1 Canete Crespillo Investigator Barcelona Barcelona, Cataluna, Spain, 08036 Dr. Lourdes Mateo Principal Hospital Germans Trias i Pujol Spain 4 Soria Investigator Badalona, Barcelona, Spain, 08916 Dr. Jesus Principal Hospital De Bellvitge Spain 2 Rodriguez Moreno Investigator L Hospitalet de Llobregat, Barcelona, Spain, 08907 Dra. Sagrario Principal Hospital Universitario General de Spain 4 Bustabad Investigator Canarias La Laguna, , Spain, 38320 Dr. Eugenio Principal Hospital de Merida Spain 3 Chamizo Carmona Investigator Merida, Badajoz, Spain, 06800 Dr. Francisco Principal Hospital Miguel Servet Spain 0 Javier Manero Ruiz Investigator , Spain, 50009 Dr. Jose Luis Principal Hospital 12 de Octubre Spain 4 Pablos Investigator , Spain, 28041 Dr. Carlos Principal Hospital Gregorio Maranon Spain 0 Gonzalez Investigator Madrid, Fernandez Spain, 28007 Dr. Francisco Principal Hospital Universitario A Coruna Spain 4 Javier Blanco Investigator La Coruna, Galicia, Spain, 15006 Dr. Ricardo Blanco Principal Hospital Universitario Marques de Spain 6 Investigator Valdecilla e IDIVAL Santander, Cantabria, Spain, 39008 Dr. Mari Luz Principal Hospital Universitario de Basurto Spain 9 Garcia Vivar Investigator Bilbao Bizkaia, Pais Vasco, Spain, 48013 Dr. Antonio Mera Principal Hospital Clinico Universitario de Spain 7 Investigator Santiago , Galicia, Spain, 15706 Dra Maria Dolores Principal Hospital Reina Sofia Spain 10 Lopez Montilla Investigator Cordoba, Andalucia, Spain, 14004 Dr. Jose Andres Principal Hospital Universitario i Politecnico La Spain 5 Roman Investigator Fe , Comunidad Valenciana, Spain, 46026 Dr. Ana Laiz Principal Hospital de la Santa Creu i Sant Pau Spain 0 Alonso Investigator Barcelona, Espana, Spain, 08026 Dr. Jose Luis Principal Hospital Univ Nuestra Sra de Valme Spain 4 Marenco Investigator Sevilla, Spain, 41014

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Dr. Juan Povedano Principal Hospital Universitario Virgen del Rocio Spain 1 Investigator Sevilla, Spain, 41013 Dr. Azucena Principal Complejo Hospitalario de Toledo Spain 0 Hernandez Investigator Toledo, Spain, 45004 Dr. Juan Jose Principal Hospital Doctor Peset Spain 3 Alegre Sancho Investigator Valencia, Comunidad Valenciana, Spain, 46017 Dr. Antonio Principal Hospital Civil de Malaga Carlos Haya Spain 3 Fernandez Nebro Investigator Malaga, Andalucia, Spain, 29009 Dr. Raul Veiga Principal Hospital Universitario de Fuenlabrada Spain 4 Cabello Investigator Madrid, Spain, 28942 Dr. Hector Chinoy Principal Salford Royal NHS Foundation Trust United Kingdom 0 Investigator Salford, Manchester, United Kingdom, M6 8HD Dr. Sophia Khan Principal Solihull Hospital United Kingdom 2 Investigator Solihull, United Kingdom, B91 2JL Dr. Hasan Inmam Principal Whipps Cross Hospital United Kingdom 0 Sayed Tahir Investigator Leytonstone, , United Kingdom, E11 1NR Dr Ben Thompson Principal Freeman Hospital United Kingdom 2 Investigator Newcastle Upon Tyne, United Kingdom, NE7 7DN Dr. Bruce Kirkham Principal Guys Hospital and St Thomas NHS United Kingdom 0 Investigator Trust London, United Kingdom, SE1 9RT Dr Nick Viner Principal Derriford Hospital United Kingdom 0 Investigator Plymouth, United Kingdom, PL6 8DH Dr. Kirsten Principal Torbay and South Devon NHS United Kingdom 0 Mackay Investigator Foundation Trust Torquay, Devon, United Kingdom, TQ2 7AA Dr. Nick Barkham Principal New Cross Hospital United Kingdom 3 Investigator Wolverhampton, United Kingdom, WV10 0QP Dr. Jonathan Principal Haywood Hospital United Kingdom 0 Packham Investigator Stoke on Trent, Staffordshire, United Kingdom, ST6 7AG Dr Thomas P G Principal Cannock Chase Hospital United Kingdom 0 Sheeran Investigator Cannock, Staffordshire, United Kingdom, WS11 5XY Dr. Neil McKay Principal Western General Hospital PPDS United Kingdom 11 Investigator , United Kingdom, EH4 2XU Dr. Yusuf Patel Principal Hull Royal Infirmary United Kingdom 3 Investigator Hull, United Kingdom, HU3 2JZ Dr. Easwaradhas Principal Wigan and Leigh NHS Foundation United Kingdom 0 Gladston Chelliah Investigator Trust

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Wigan, United Kingdom, WN6 9EP Dr. Animesh Singh Principal Royal Free Hospital United Kingdom 0 Investigator London, United Kingdom, NW3 3QG Dr. Stefan Siebert Principal Glasgow Clinical Research Facility United Kingdom 4 Investigator Glasgow, United Kingdom, G31 2ER Dr Alan J Kivitz Principal Altoona Center for Clinical Research United States 0 Investigator Duncansville, PA, United States, 16635 Dr. Tina Bunch Principal Austin Regional Clinic Rheumatology United States 4 Investigator Austin, TX, United States, 78731 Dr. Bonita Libman Principal The University of Vermont Medical United States 1 Investigator Center Burlington, VT, United States, 05401 Dr. Angela Moore Principal Arlington Research Center Inc United States 4 Investigator Arlington, TX, United States, 76011 Dr. Atul K K. Principal Southwest Rheumatology Research United States 2 Singhal Investigator LLC Mesquite, TX, United States, 75150 Dr. Shirley Pang Principal St Joseph Heritage Healthcare United States 1 Investigator Fullerton, CA, United States, 92835 Dr. Kathryn Dao Principal Arthritis Care & Research Center United States 2 Investigator Dallas, TX, United States, 75231 Dr. John H Tu Principal Skinsearch of Rochester Inc United States 0 Investigator Rochester, NY, United States, 14623 Dr. Jeffrey B Principal Arthritis Northwest PLLC United States 2 Butler Investigator Spokane, WA, United States, 99204 Dr. Asad Fraser Principal Graves Gilbert Clinic United States 1 Investigator Bowling Green, KY, United States, 42101 Dr. Philip J Mease Principal Seattle Rheumatology Associates United States 0 Investigator Seattle, WA, United States, 98122 Dr. Melvin Principal Physician Research Collaboration United States 6 Churchill Investigator Lincoln, NE, United States, 68516 Dr. Kurt Oelke Principal Rheumatic Disease Center United States 0 Investigator Glendale, WI, United States, 53217 Dr. William R. Principal Westroads Clinical Research, Inc United States 3 Palmer Investigator Omaha, NE, United States, 68114 Dr. Vivian Laquer Principal Tien Q Nguyen MD Inc United States 0 Investigator Fountain Valley, CA, United States, 92708

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Dr. Chad Ronholm Principal Clayton Medical Associates United States 2 Investigator St. Louis, MO, United States, 63117 Dr. Eric Lee Principal Inland Rheumatology Clinical Trials Inc United States 2 Investigator Upland, CA, United States, 91786

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2. Changes to the Study Protocol

Important changes to the study protocol after commencement of the trial (no patients were randomised at this stage) included: inclusion of additional follow-up visit, update in wording of exclusion criteria per guidelines for contraception use after the last dose of study treatment for women of childbearing potential, extension of the interruption requirement if the patient received a live vaccine underwent an update (to extend the recommended time before starting a new biologic as elimination of adalimumab may take up to 4 months).

Amendment 2 happened to clarify the estimand to align with the study objectives, which were comparing efficacy of secukinumab monotherapy with adalimumab monotherapy. Non-parametric regression1 model was not essential to the final analysis but could be performed and sensitivity analyses was to be conducted to examine the effect of taking concomitant treatment of methotrexate (MTX) and/or other conventional synthetic disease modifying antirheumatic drugs (csDMARDs) along with study drug.

None of the changes were made due to safety concerns, had an impact on the conduct of the trial, or altered the treatment of study patients. The changes occurred while the sponsor remained blinded to study data.

3. Patient Inclusion Exclusion Criteria Inclusion criteria

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

• Male or non-pregnant, non-lactating female patients at least 18 years of age. • Diagnosis of psoriatic arthritis (PsA) as classified by ClASsification of Psoriatic ARthritis (CASPAR) criteria2 and with symptoms for at least 6 months and with active PsA at baseline defined as ≥3 tender joints out of 78 and ≥3 swollen joints out of 76 (dactylitis of a digit, counts as one joint each). • Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies negative at screening. • Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥2 cm diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis. • Patients with PsA who took non-steroidal anti-inflammatory drugs (NSAIDs) for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs. • Patients who regularly received NSAIDs as part of their PsA therapy were required to be on a stable dose for at least 2 weeks before study randomization and remained on a stable dose up to Week 52. • Patients who received corticosteroids were required to be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and remained on a stable dose up to Week 52. • Patients who were previously treated with a csDMARD, including but not limited to MTX, with an inadequate response to therapy, or had stopped treatment due to safety/tolerability problems after at least one administration of the csDMARD.

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• Patients who received a csDMARD were allowed to enter the study only after csDMARD discontinuation and appropriate wash-out e.g. 4 weeks prior to randomization visit except for leflunomide, which had to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out was performed. Exclusion criteria

Patients fulfilling any of the following criteria were not eligible for inclusion in this study.

• Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. • Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using effective methods of contraception during dosing of study treatment and minimum 16 weeks or longer if local label required it after the last dose (e.g. 20 weeks for secukinumab, 5 months for adalimumab in Europe). Effective contraception methods included: o Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. o Female sterilization (had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment. o Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that subject. o Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). o Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that had comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception, women who had been stable on the same pill for a minimum of 3 months before taking investigational drug. Women were considered post-menopausal and not of child bearing potential if they had at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment was she considered not of childbearing potential. • Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process obtained within 3 months prior to screening and evaluated by a qualified physician. • Previous exposure to any biologic drugs for PsA and PSO, including but not limited to TNFα inhibitors, secukinumab or other biologic drugs targeting IL-17 or IL-17 receptor.

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• Patients who received high-potency opioid analgesics, including but not limited to, methadone, hydromorphone, and morphine. • Ongoing use of prohibited psoriasis treatments/medications (e.g., topical corticosteroids or ultraviolet (UV) therapy at randomisation). The following wash out periods need to be observed: o Oral or topical retinoids: 4 weeks. o Photochemotherapy (e.g., PUVA): 4 weeks. o Phototherapy (UVA or UVB): 2 weeks. o Topical skin treatments (except in face, eyes, scalp and genital area during screening; only corticosteroids with mild to moderate potency): 2 weeks. • Previous treatment with any cell-depleting therapies, including but not limited to anti-CD20 or investigational agents (e.g., alemtuzumab (Campath®), anti-CD4, anti-CD5, anti-CD3, and anti-CD19). • Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect had returned to baseline, whichever is longer. • History of hypersensitivity to any of the study drugs or excipients or to drugs of similar chemical classes. • Any intramuscular or intravenous corticosteroid treatment within 4 weeks before randomization. • Any therapy by intra-articular injections (e.g., corticosteroid) within 4 weeks before randomization. • Active ongoing inflammatory diseases other than PsA that had confound the evaluation of the benefit of secukinumab therapy. • Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromised the patient and/or placed the patient at unacceptable risk for participation in an immunomodulatory therapy. • Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥160/95 mmHg), congestive heart failure (New York Heart Association status of class III or IV) and uncontrolled diabetes. • History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFTs) such as aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/ serum glutamic pyruvictransaminase (ALT/SGPT), alkaline phosphatase or serum bilirubin. The investigator was guided by the following criteria: o Any single parameter not exceeding 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN was re-checked once more as soon as possible and in all cases, at least prior to enrollment/randomization, to rule out any possible lab error. o If the total bilirubin concentration was increased above 2 x ULN, total bilirubin was differentiated into the direct and indirect reacting bilirubin. • History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.5 mg/dL (132.6 μmol/L). • Screening total white blood cell (WBC) count <3,000/μL, or platelets <100,000/μL or neutrophils <1,500/μL or hemoglobin <8.5 g/dL (85 g/L).

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• Active systemic infections during the last two weeks (exception: common cold) prior to randomization. • History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive purified protein derivative (PPD) skin test (the size of induration was measured after 48- 72 hours, and a positive result was defined as an induration of ≥ 5mm or according to local practice/guidelines), or a positive QuantiFERON TB-Gold test. Patients with a positive test were to participate in the study if further work up (according to local practice/guidelines) established conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis was established then treatment according to local country guidelines were initiated prior to enrollment. • Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at screening or randomization. • History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratoses that had been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that had been removed). • Current severe progressive or uncontrolled disease, which in the judgment of the clinical investigator rendered the patient unsuitable for the trial. • Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins). • Any medical or psychiatric condition, which in the investigator’s opinion precluded the patient from adhering to the protocol or completing the study per protocol. • Donation or loss of 400 mL or more of blood within 8 weeks before randomisation. • History or evidence of ongoing alcohol or drug abuse, within the last six months before randomisation. • Plans for administration of live vaccines during the study period or within 6 weeks preceding randomisation. 4. Randomisation and blinding At baseline, all eligible patients were randomised via interactive response technology (IRT) to one of the two treatment groups: (secukinumab 300 mg s.c. or adalimumab 40 mg s.c.). A designated Site-staff member other than the investigator or study staff involved in safety and efficacy assessments or eCRF completion contacted IRT after confirming that the patient fulfilled all the inclusion/exclusion criteria. The IRT assigned a randomisation number to the patient, which was used to link the patient to a treatment arm and specified a unique medication number for the first package of investigational treatment to be dispensed to the patient. The randomisation number was not to be communicated to the investigator or study site staff involved in the conduct of efficacy assessments. This was a double-blind randomised treatment trial. Patients, investigators, site personnel, and persons performing the assessments (except for those described below) remained blinded to treatment assignment from the time of randomisation until the database lock and analyses were completed, using the following methods: Randomisation data are kept strictly confidential until the time of unblinding and were not be accessible by anyone else involved in the study with the exception of the bioanalyst. Investigational treatment was to be dispensed by an unblinded pharmacist (or other unblinded qualified site personnel) who was independent of those involved in the assessment of study

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patients. In addition, the unblinded pharmacist (or other unblinded qualified site personnel) stored study medication and kept medication records containing unblinded information in a separate area to which blinded staff did not have access.

Study treatment was administered by “independent study drug administrator”- an unblinded suitably qualified individual (nurse, physician, or other unblinded qualified site personnel) who was not responsible for any aspect of patient assessment or follow-up. “Independent study drug administrator” could be the same person dispensing the drug if suitably qualified to perform both activities. Prior to the administration, the unblinded site personnel put in place suitable methods, e.g physical barriers such as curtains, blindfolds, or similar as agreed with the patient and available to prevent patient seeing the appearance of their study treatment. The individual administering study treatment and all study patients were advised to refrain from making any comments to study staff or to other patients regarding the appearance of study treatments.

5. Outcomes The efficacy outcome measures used in this study are standard measures used across all PsA trials:

• American College of Rheumatology (ACR) 20, 50 and 70 responses • Swollen Joint Count (SJC)/Tender Joint Count (TJC) • Patient’s global assessment of disease activity (VAS) • Physician’s global assessment of disease activity (VAS) • Patient’s assessment of PsA pain intensity (VAS) • Health Assessment Questionnaire – Disability Index (HAQ-DI©) • high sensitivity C-Reactive Protein (hsCRP) and Erythrocyte Sedimentation Rate (ESR) • Psoriatic arthritis response criteria (PsARC) response • Disease Activity Score (DAS28) and EULAR response criteria • Psoriatic Arthritis Disease Activity Score (PASDAS) • Patient’s global assessment of psoriasis and arthritis disease activity (VAS) • Leeds Dactylitis Index (LDI) • Leeds Enthesitis Index (LEI) • Spondyloarthritis Research Consortium of Canada (SPARCC) index • Psoriasis Area and Severity Index (PASI) • Modified Composite Psoriatic Disease Activity Index (mCPDAI) Safety Outcomes

Evaluation of adverse events/serious adverse events

• Physical examination • Vital signs • Height and weight • QuantiFERON TB-Gold test or PPD skin test

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• Electrocardiogram • Local tolerability (injection site reactions) • Laboratory evaluations (hematology, clinical chemistry, lipids) • Pregnancy and assessment of fertility • Tolerability of study treatment • Immunogenicity References.

1. Koch GG, Tangen CM, Jung JW, et al. Issues for covariance analysis of dichotomous and ordered categorical data from randomized clinical trials and non-parametric strategies for addressing them. Stat Med 1998; 17: 1863-92. 2. Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54(8): 2665-73.

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SUPPLEMENTARY FIGURES AND TABLES

Figure S1. Study Design and Hierarchical Testing

n, number of patients ACR, American college of rheumatology; BL, baseline; DMARD-IR, disease modifying anti-rheumatic drugs-inadequate responders; HAQ-DI, health assessment quality-disability index; PASI, psoriasis activity severity index; s.c., subcutaneous; PsA, psoriatic arthritis

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Figure S2. Patient Study Treatment Disposition up to Week 50

Wk, week N, number of randomised patients; n, number of available patients

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Figure S3. Kaplan Meier Time to Study Treatment Discontinuation Curve

p value versus adalimumab

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Table S1. Efficacy in Patients with Psoriasis (BSA>10% or PASI ≥10)

Endpoints, data is presented as % response SEC 300 mg ADA 40 mg Odds Ratio 95% CI p-value* (N = 110) (N = 101)

ACR20 76 68 1·53 0·83, 2·83 0·1752

PASI 90 69 42 3·21 1·80, 5·71 <0·0001

ACR50 55 49 1·28 0·73, 2·22 0·3866

HAQ-DI (>=0.35) 57 55 1·2 0·67, 2·14 0·5321

Resolution of enthesitis (based on LEI) 75 66 1·54 0·85, 2·82 0·1571

ACR50 + PASI 100 28 18 1·92 0·97, 3·79 0·0604

DAS-28 CRP low disease activity 82 64 2·58 1·34, 4·97 0·0046

DAS28-CRP based remission 58 51 1·34 0·76, 2·38 0·3095

ACR70 31 29 1·14 0·62, 2·08 0·6734

Resolution of dactylitis 91 81 2·39 1·05, 5·45 0·0379

PASI 75 87 60 5·02 2·48, 10·19 <0·0001

PASI 100 39 24 2·15 1·17, 3·96 0·0136

*Unadjusted p values versus adalimumab N, number of patients in with psoriasis with BSA>10% or PASI ≥10 ACR, American college of rheumatology; ADA, adalimumab; BSA, body surface area; CI, confidence interval; CRP, C-reactive protein; DAS28, disease activity score based on 28 joint count; DAPSA, disease activity in psoriatic arthritis; HAQ-DI, health assessment questionnaire-disability index; LEI, Leeds enthesitis index; MI, multiple imputation; PASI, psoriasis area severity index; SEC, secukinumab

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Table S2. Details of Serious Infections

Secukinumab 300 mg (N = 426) Adalimumab (N = 427)

Infections and infestations, n 7 6

Appendicitis 1 0 Chronic sinusitis 1 0 Gastroenteritis salmonella 1 0 Influenza 1 0 Lower respiratory tract infection fungal 1 0 Pilonidal cyst 1 0 Tonsillitis 1 0 Bursitis infective 0 1 Diverticulitis 0 1 Labyrinthitis 0 1 Measles 0 1 Mycobacterial infection 0 1 Pneumonia 0 1 Preferred terms were sorted within primary system organ class in descending order of frequency in the Secukinumab 300 mg column A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment A patient with multiple adverse events within a primary system organ class is counted only once in the total row MedDRA version 22.0 was used for reporting

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Table S3 Details on Protocol Deviation

Secukinumab (N = 426) Adalimumab (N = 427) Patients with at least one protocol deviation, n (%) 172 (40) 165 (39) Protocol deviations, n (%) Selection criteria not met 37 (9) 37 (9) Patient not withdrawn as per protocol 0 0 Key procedures not performed as per protocol 0 0 Treatment deviation 3 (1) 4 (1) *Prohibited concomitant medication 84 (20) 95 (22) Other GCP deviation 92 (22) 79 (19) *Not related to csDMARD use except 3 patients who took csDMARDs before Week 36 whilst on study treatment

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Table S4 Absolute and relative frequencies for treatment emergent serious adverse events by primary system organ class and preferred term up to Week 52

Secukinumab 300 mg Adalimumab 40 mg N=426 N=427 Primary system organ class Preferred term n n Any primary system organ class -Total 32 28 Blood and lymphatic system disorders -Total 2 0 Anaemia 1 0 Lymphadenopathy 1 0 Cardiac disorders -Total 3 2 Acute myocardial infarction 1 0 Myocardial infarction 1 0 Pericarditis 1 0 Angina pectoris 0 1 Cardiac failure acute 0 1 Gastrointestinal disorders -Total 4 3 Abdominal pain 1 0 Abdominal pain upper 1 0 Colitis ulcerative 1 0 Diarrhoea 1 0 Abdominal wall haematoma 0 1 Splenic artery aneurysm 0 1 Umbilical hernia 0 1 General disorders and administration site conditions -Total 1 0 Chest pain 1 0 Hepatobiliary disorders -Total 1 0 Cholecystitis 1 0 Infections and infestations -Total 7 6 Appendicitis 1 0

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Secukinumab 300 mg Adalimumab 40 mg N=426 N=427 Primary system organ class Preferred term n n Chronic sinusitis 1 0 Gastroenteritis salmonella 1 0 Influenza 1 0 Lower respiratory tract infection fungal 1 0 Pilonidal cyst 1 0 Tonsillitis 1 0 Bursitis infective 0 1 Diverticulitis 0 1 Labyrinthitis 0 1 Measles 0 1 Mycobacterial infection 0 1 Pneumonia 0 1 Injury, poisoning and procedural complications -Total 6 4 Burns second degree 1 0 Concussion 1 0 Foot fracture 1 0 Joint dislocation 1 0 Post procedural haematoma 1 0 Post-traumatic neck syndrome 1 0 Skin laceration 1 0 Wound 1 0 Epicondylitis 0 1 Hand fracture 0 1 Tibia fracture 0 1 VIIIth nerve injury 0 1 Musculoskeletal and connective tissue disorders -Total 4 3 Osteoarthritis 1 1 Cervical spinal stenosis 1 0 Intervertebral disc protrusion 1 0 Synovitis 1 0 Foot deformity 0 1

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Secukinumab 300 mg Adalimumab 40 mg N=426 N=427 Primary system organ class Preferred term n n Psoriatic arthropathy 0 1 Neoplasms benign, malignant and unspecified (incl cysts and polyps) -Total 3 3 Colon cancer 1 0 Plasma cell myeloma 1 0 Uterine leiomyoma 1 0 Leiomyoma 0 1 Non-Hodgkin's lymphoma 0 1 Synovial sarcoma 0 1 Nervous system disorders -Total 1 3 Syncope 1 0 Paraesthesia 0 1 Radiculopathy 0 1 Transient ischaemic attack 0 1 Psychiatric disorders -Total 0 1 Alcohol abuse 0 1 Depression 0 1 Reproductive system and breast disorders -Total 2 3 Endometrial hypertrophy 1 0 Ovarian cyst 1 0 Prostatitis 0 2 Uterine polyp 0 1 Respiratory, thoracic and mediastinal disorders -Total 3 2 Pulmonary embolism 1 1 Dyspnoea 1 0 Epistaxis 1 0 Sleep apnoea syndrome 1 0 Alveolitis 0 1

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Secukinumab 300 mg Adalimumab 40 mg N=426 N=427 Primary system organ class Preferred term n n Haemoptysis 0 1 Skin and subcutaneous tissue disorders -Total 2 1 Drug reaction with eosinophilia and systemic symptoms 1 0

Skin ulcer 1 0 Perioral dermatitis 0 1 Vascular disorders -Total 1 1 Peripheral arterial occlusive disease 1 0 Aortic aneurysm 0 1

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