Objectives To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).
Methods Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24.
Results The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients.
Conclusions IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
- psoriatic arthritis
- clinical trial
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Handling editor David S Pisetsky
Collaborators The SPIRIT H2H study group are collaborators. The SPIRIT H2H study group includes: Leonardo Naftal, Rodolfo Ariel Pardo Hidalgo, Eduardo Mario Kerzberg, Veronica Gabriela Savio, Alicia Lazaro, Benito Jorge Velasco, Norma Beatriz Verzero, Cecilia Adma Asnal, Eduardo Fabian Mysler, Alberto Berman, Federico Javier Ariel, Maureen Rischmueller, Jane Margaret Zochling, Paul A Bird, Stephen Hall, Andrew Ostor, Evange Romas, Georg Stummvoll, Klaus Machold, Peter Spellitz, Ursula Hanusch, Marc Vanden Berghe, Marc Leon, Johan Louis Magda Vanhoof, Filip Eduard Jeanne Van den Bosch, Kurt Leo Francois De Vlam, Frederic Morin, Louis Bessette, Derek A Haaland, Annette Margrethe Schlemmer, Lars Erik Kristensen, Pentti Jarvinen, Ritva Liisa Peltomaa, Laura Pirila, Jorma Vuotila, Eric Lespessailles, Philippe Goupille, Bernard Combe, Arnaud Constantin, Gregoire Cormier, Celine Cozic, Cyrille B Confavreux, Hendrik Schulze-Koops, Andrea Everding, Micheala Kohm, Siegfried Wassenberg, Magdolna Nagy, Noemi Bakos, Eva Melegh, Edit Drescher, Lalit Duggal, Piyush Narayanbhai Joshi, Srabani Ghosh Zoha, A Ramakrishnam Naidu, Puja Pushkarkumar Srivastava, Vishnu Devkinandan Sharma, Ajit Bapurao Nalawadae, Jyotsna Laxmikant Oak, Sarath Chandra Mouli Veeravalli, Jugal Kishore Kadel, Manisha Ashwin Daware, Yogesh S Marfatia, Sumeet Agarwal, Yolanda Braun Moscovici, Ori Elkayam, Yair Molad, Tatiana Reitblat, Moshe Tishler, Yair Levy, Merav Lidar, Devy Zisman, Antonio Costanzo, Paolo Amerio, Riccardo Meliconi, Rosario Foti, Roberto Perricone, Maurizio Rossini, Elisa Gremese, Beatriz Elena Zazueta Montiel, Juan Manuel Miranda Limon, Marco Antonio Maradiaga Cecena, Sandra Araceli Sicsik Ayala, Miguel Angel Alvarez Guerrero, Jorge Rojas Serrano, Efren Antonio Canul Novelo, Francisco Fidencio Cons-Molina, Ed N Griep, Andrzej Kaszuba, Jolanta Bogna Węgłowska, Barbara Bazela, Maria Rell-Bakalarska, Malgorzata Miakisz, Catherine Elizabeth Spargo, Elsa Margaretha Van Duuren, Asokan Naidoo, Nomawethu Cleopatra Matsiliza, Johannes Breedt, Gareth Scott Tarr, Jenny Potts, Savithree Nayiager, Mahmood Moosa Tar Mahomed Ally, Francisco Javier Blanco Garcia, Antonio Mera Varela, Jose Rosas, Juan Miguel Sanchez Burson, Javier Garcia Miguel, Jon Lampa, Milad Rizk, Giovanni Cagnotto, Per Larsson, Guozhong Fei, Ruediger Mueller-Mar, Andrea Rubbert-Roth, Michael John Nissen, Oleh Iaremenko, Svitlana Anatoliivna Trypilka, Dmytro Rekalov, Mykola Stanislavchuk, Viktoriia Viktorivna Vasylets, Olena Garmish, Svitlana Smiyan, David Walker, Deepak Jadon, Stuart Ralston, Stephen Boyle, Pippa Anne Watson, James E Dale, Sara Carty, Karen Douglas, Christopher J Edwards, David Hutchinson, Nick Barkham.
Contributors All authors contributed to critical revision of the manuscript and gave final approval for submission for publication. PJM, JSS, FB, EK and HL-S contributed to interpretation of data. PN contributed to study conception, data acquisition and interpretation of data. SLL contributed to study conception, analysis of data and interpretation of data. LL and PE contributed to analysis of data and interpretation of data. HT, MG, SP and PSH contributed to acquisition of data and interpretation of data.
Funding This study was funded by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation and publication decisions.
Competing interests PJM reports research grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen and Lilly; and personal fees from Boehringer Ingelheim, Galapagos, Genentech and Gilead. JSS reports research grants from AbbVie, Astra-Zeneca, Janssen, Lilly, MSD, Novartis, Pfizer and Roche; and personal fees from AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB. FB reports research grants from Pfizer, Janssen, Chugai, Celgene and Roche; personal fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai; and investigator fees from Lilly. PN reports research grants and personal fees from AbbVie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Celgene, Gilead, Sanofi, UCB and Roche. HT reports research grants and non-financial support from Lilly. MG reports personal fees from AbbVie, Actelion Pharmaceuticals, Akros Pharma Inc, AMGEN Inc, Arcutis Pharmaceuticals Inc, Boehringer Engelheim International GmbH, Bristol-Myers Squibb Company, Celgene corporation, Dermira Inc, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Jannsen Inc, LEO Pharma, MedImmune, Merck and Co, Novartis Pharmaceuticals, Pfizer Inc, Regeneron Pharmaceuticals Inc, Roche Laboratories, Sanofi Genzyme, UCB and Valeant Pharmaceuticals Inc. PE has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly; has received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche and UCB; and has received research grants paid to his employer from AbbVie, BMS, Pfizer, MSD and Roche. PSH reports research grants, personal fees and non-financial support from AbbVie; research grants from Amgen, Janssen, Pfizer and UCB; and personal fees from Lilly and Galapagos. SLL, LL, EK, HL-S and SP are employees of, and own stock in, Eli Lilly and Company.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.
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