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Randomized Controlled Trial
. 2020 Jan;79(1):123-131.
doi: 10.1136/annrheumdis-2019-215386. Epub 2019 Sep 28.

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial

Philip J Mease  1 , Josef S Smolen  2 , Frank Behrens  3 , Peter Nash  4 , Soyi Liu Leage  5 , Lingnan Li  5 , Hasan Tahir  6 , Melinda Gooderham  7 , Eswar Krishnan  5 , Hong Liu-Seifert  5 , Paul Emery  8   9 , Sreekumar G Pillai  5 , Philip S Helliwell  8 ; SPIRIT H2H study group
Affiliations
Randomized Controlled Trial

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial

Philip J Mease et al. Ann Rheum Dis. 2020 Jan.

Abstract

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.

Keywords: adalimumab; clinical trial; head-to-head; ixekizumab; psoriatic arthritis.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Participant flow diagram up to week 24.
Figure 2
Figure 2
Clinical response rates for primary and major secondary outcomes through week 24 (non-responder imputation). (A) Percentage of patients simultaneously achieving ACR50 and PASI100 (primary endpoint). (B) Percentage of patients achieving ACR50 (major secondary endpoint). The treatment difference of IXE minus ADA was 3.9% (95% CI −4.3% to 12.1%). The lower bound of the 95% CI (−4.3%) was greater than −12%, thus meeting noninferiority criteria. (C) Percentage of patients achieving PASI100. IXE versus ADA: *P<0.05, †p<0.01, ‡p<0.001. ACR, American College of Rheumatology; ADA, adalimumab; IXE, ixekizumab; PASI, Psoriasis Area Severity Index.
Figure 3
Figure 3
Clinical response rates for treat-to-target outcomes through week 24. (A) Percentage of patients achieving minimal disease activity. (B) Percentage of patients achieving very low disease activity. (C) Percentage of patients achieving a DAPSA score of ≤14 (LDA or remission). (D) Percentage of patients achieving a DAPSA score ≤4 (remission). IXE versus ADA: *P<0.05, †p<0.01, ‡p<0.001. ADA, adalimumab; DAPSA, Disease Activity in Psoriatic Arthritis; IXE, ixekizumab; LDA, low disease activity.
See this image and copyright information in PMC

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