Abstract 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 IXE-treated 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. Disclosures H. Tahir: Consultancies; Novartis, Eli-Lilly, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. J.S. Smolen: Consultancies; AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Medimmune, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. Grants/research support; AbbVie, Eli Lilly, Novartis, Pfizer, Roche. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. C.F. Dionello: Consultancies; Novartis, Lilly, Janssen, Abbvie. Honoraria; Novartis, Lilly, Janssen, Abbvie, Roche, Pfizer. G. Meszaros: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly.