Multicentre, randomised, open-label, assessor-blinded, parallel-group head-to-head comparison of the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naive to biologic disease-modifying anti-rheumatic drugs: 24-week results

Background: There have been few head-to-head clinical trials comparing different biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients (pts) with psoriatic arthritis (PsA). Objectives: To report 24-week (wk) results of a study directly comparing efficacy and safety of ixekizumab (IXE), an IL-17A inhibitor, and adalimumab (ADA), a TNF inhibitor, in bDMARD-naive pts with PsA. Methods: The study (NCT03151551; SPIRIT-H2H) included pts with active PsA (≥3 TJC + ≥3SJC) and plaque psoriasis (BSA≥3%) who were bDMARD naive and inadequate responders to csDMARD therapy. Patients were randomised (1:1) to IXE or ADA for 52 wks (on-label dosing based on presence/absence of moderate to severe psoriasis). The primary objective was superiority of IXE vs ADA measured by the proportion of pts achieving both ACR50 and PASI100 responses at wk24. Key secondary objectives versus ADA at wk 24 were (1) non-inferiority of IXE for ACR50 (noninferiority margin -12%) and (2) superiority of IXE for PASI100. Additional PsA, skin, composite treat-to-target (T2T: MDA, DAPSA 4), PASDAS remission and patient-reported outcomes, and safety were assessed. Nine pts had PASI=0 and BSA≥3% (a medical inconsistency) at baseline; these pts were considered PASI100 responders if PASI=0 and BSA=0 at wk 24. Categorical variables were evaluated using logistic regression analyses with NRI in the ITT population. Continuous variables were analysed using mixed models for repeated measure analysis. Results: 566 pts were randomised (283 to IXE and 283 to ADA). Baseline demographics and disease characteristics were generally well balanced between groups (Table 1). All primary and key secondary efficacy endpoints at wk 24 were met (Figure). The proportion of pts achieving both ACR50 and PASI100 was significantly greater for IXE than ADA (36% vs 28%; p<0.05). IXE was non-inferior to ADA for ACR50 response and superior for PASI100 response (Figure). While improvements from baseline were achieved with both treatments, significantly better results were seen with IXE vs ADA for skin and composite T2T outcomes, enthesitis resolution (Figure 1), and skin-related quality of life (Table 2). No unexpected safety signals were observed. (Table Presented) Conclusion: In bDMARD naive pts with active PsA and skin disease, IXE showed superior efficacy to ADA based on simultaneous achievement of ACR50 and PASI100 responses at wk 24. Greater improvements with IXE vs ADA were also attained in individual PsA domains and composite T2T outcomes.