Efficacy of ixekizumab vs. adalimumab in patients with psoriatic arthritis with moderate-to-severe psoriasis: 52-week results from a multicentre, randomized, open-label study

Ixekizumab (IXE), a selective interleukin 17A antagonist, is approved for the treatment of adults with moderate‐to‐severe psoriasis (PsO), and active psoriatic arthritis (PsA). The efficacy of IXE was compared with adalimumab (ADA) in patients with PsA and concomitant PsO in the SPIRIT‐H2H (NCT03151551) study. SPIRIT‐H2H was a multicentre, randomized, open‐label, rater‐blinded, parallel‐group study. Biological disease‐modifying anti‐rheumatic drug (DMARD)‐naïve patients (n = 566) with PsA and active PsO [≥ 3% body surface area (BSA) involvement] were randomized to IXE or ADA, stratified by concomitant use of conventional synthetic DMARDs and severity of PsO. Patients with moderate‐to‐severe PsO [Psoriasis Area Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and BSA involvement ≥ 10%] received either IXE [160 mg at week 0, 80 mg every 2 weeks (Q2W) up to week 12 then every 4 weeks] or ADA (80 mg at week 0, 40 mg Q2W starting at week 1). The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement from baseline in PASI (PASI100) at week 24. Here we report efficacy outcomes between IXE and ADA, compared using Fisher's exact test, through week 52 in a subgroup of patients with moderate‐to‐severe PsO. Missing data were imputed using nonresponder imputation. At baseline, 49 of 283 IXEand 51 of 283 ADA‐treated patients had concomitant moderate‐to‐severe PsO. Of these, 40.8% of patients treated with IXE and 17.6% treated with ADA achieved the primary endpoint at week 24 (P = 0.015). At week 52, 38.8% of IXE‐ and 17.6% of ADA‐treated patients concomitantly achieved ACR50 and PASI100 (P = 0.026). Regarding efficacy endpoints for PsA, the proportion of patients achieving ACR20/ACR50/ACR70 was 73.5%, 55.1% and 42.9% for IXE vs. 80.4%, 62.7% and 39.2% for ADA, respectively (P = 0.480; P = 0.542; P = 0.839). Complete skin clearance, as measured by PASI100, was reached in 59.2% of IXE‐ and 25.5% of ADA‐treated patients (P = 0.001). PASI90 response rates were significantly higher with IXE compared with ADA (81.6% vs. 60.8%; P = 0.028), while no significant differences were seen in PASI75 response rates (85.7% vs. 80.4%; P = 0.597). Other secondary endpoints, including the proportions of patients achieving a Dermatology Life Quality Index of 0 or 1, and complete clearance of nail psoriasis, were numerically higher in the IXE than ADA group, but were not significantly different. In patients with PsA and moderate‐to‐severe PsO, the significantly greater combined response (ACR50 + PASI100) shown for IXE at week 24 was sustained through week 52 and was consistent with results observed in the overall SPIRIT study population.