Comparative effects of ixekizumab (IXE) vs adalimumab (ADA) across psa patients defined by baseline characteristics: Week 24 outcomes from spirit-H2H

Background: Comparisons of PsA treatment options to guide physicians are limited. When conventional treatment is insufficient, the recommendations is a biological agent, most frequently tumour necrosis factor (TNF)-inhibitors. IXE, an IL-17A antagonist biologic, showed superiority over TNF-inhibitor ADA for the simultaneous achievement of ACR50 and PASI100, and PASI100 alone in the SPIRIT-H2H trial at week 24. We analysed differences in efficacy outcomes between IXE and ADA by subgroups based on baseline clinical characteristics. Methods: We conducted post-hoc analysis of data from SPIRIT-H2H (NCT03151551), a 52-week, multicentre, open-label, blinded assessor study patients with active PsA (defined as swollen joint count ≥3 and tender joint count ≥3), with a body surface area (BSA) ≥3% and insufficient response to≥1 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and naïve to biologic (b)-DMARDs. Patients were randomised 1:1 to IXE or ADA, while presence/absence of moderate-to-severe psoriasis (defined as PASI ≥12, static Physician Global Assessment ≥3 and BSA ≥10%) determined on-label dosing. Subgroups were defined by baseline enthesitis, dactylitis, fingernail psoriasis (presence/absence), BSA (<10%, ≥10%) and CRP (≥ 6 mg/ L,>6 mg/L). A Fisher's exact test was used for between group comparisons of efficacy outcome measures at 24 weeks (PASI90, ACR50/70, and minimal disease activity [MDA]). Missing data were overcome by non-responder imputation. Results: At week 24, IXE and ADA demonstrated comparable efficacy in ACR50 response rates across all subgroups. ACR70 response in patients with fingernail psoriasis was significantly greater with IXEtreated vs ADA (p=0.02) (table). PASI90 response with baseline enthesitis (p<0.001), without dactylitis (p<0.001), with fingernail psoriasis (p<0.001), CRP (≥6 mg/L, p=0.003; >6 mg/L, p=0.036) and BSA (<10%, p=0.010; ≥10%, p=0.003) was significantly greater in IXE vs ADA (table). Significantly more IXE-treated patients vs ADA achieved MDA with baseline enthesitis (p=0.002), without dactylitis (p=0.015), with fingernail psoriasis (p<0.001), CRP ≥6 mg/L (p=0.046) and BSA ≥10% (p=0.01) (table). A limitation is that this analysis was completed post-hoc, not controlled for multiplicity, and patients were not stratified by baseline disease characteristics. Conclusion: IXE and ADA are associated with comparable efficacy and associated with a greater effect in certain subgroups. Results will aid clinicians when making treatment choices.