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

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.

Figure 1

Participant flow diagram up to week 24.

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

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.