Abstract Background/Aims Among adults with psoriatic arthritis (PsA) in the SPIRIT H2H study, 65% had nail psoriasis (PsO) at baseline and of these, 96.2% had simultaneous distal interphalangeal joint (DIP) disease in ≥ 1 digits at baseline. This analysis describes the impact of ixekizumab (IXE) and adalimumab (ADA) on quality of life (QoL), function and joint pain. Methods This post-hoc analysis included patients from SPIRIT-H2H (NCT03151551) treated with either IXE or ADA who had simultaneous nail and DIP involvement (swelling or tenderness) in ≥ 1 digits at baseline. Nail PsO was measured using Nail Psoriasis Severity Index (NAPSI). Joint involvement was measured by tender/swollen joint count scores. Joint pain was measured by patient’s assessment of pain using Visual Analogue Scale (100 mm). QoL measures included Dermatology Life Quality Index (DLQI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 Mental and Physical Component Summary Scores (SF-36 MCS/PCS). Patients were evaluated at baseline and Week 4, 8, 12, 16, 24, 32, 40, and 52. Joint pain and SF-36 MCS/PCS changes from baseline were analysed using a mixed effects model of repeated measures. Proportions of patients achieving DLQI ≤1 or HAQ-DI change ≥0.35 (minimal clinically important difference) were analysed using logistic regressions. Non-responder imputation and modified baseline observation carried forward methods were used for missing data. Results 354 SPIRIT-H2H patients had a NAPSI total score >0 and DIP involvement in ≥ 1 digits simultaneously at baseline (IXE, N = 186 and ADA, N = 168). Among them, IXE-treated patients had a significant improvement in joint pain at Week 4 and a larger improvement in joint pain over 52 weeks vs ADA-treated patients. In addition, a larger proportion of IXE-treated patients achieved a DLQI score of 0 or 1, and these statistically significant differences were observed as early as Week 4 and sustained at each visit over 52 weeks. IXE-treated patients also experienced statistically significant improvements in SF-36 MCS at Week 4, 12 and 32 compared to ADA-treated patients; numerically greater improvements in favor of IXE were sustained at all other visits. IXE-treated patients showed a larger improvement in SF-36 PCS over 52 weeks vs ADA-treated patients, and these differences reached statistical significance at Week 24 and 32. Similar proportions of patients treated with IXE or ADA showed a clinically important improvement in HAQ-DI. Conclusion In patients with simultaneous nail and DIP involvement in ≥ 1 digit at baseline, IXE treatment resulted in significant improvements across multiple QoL measures, and greater improvements in joint pain compared to ADA treatment. These data may help health care providers make clinical decisions concerning the care of PsA in patients with nail and DIP involvement. Disclosure C. Ritchlin: Consultancies; C. Ritchlin has received consulting fees and/or honoraria and/or grant support from: AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB Pharma. A. Kavanaugh: Consultancies; A. Kavanaugh has received consulting fees and/or honoraria from: AbbVie, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB Pharma. L. Kristensen: Consultancies; L.E. Kristensen has received consulting fees and/or honoraria and/or research support from: Pfizer, AbbVie, Amgen, UCB Pharma, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. J. Merola: Consultancies; J. F. Merola is a consultant and/or investigator for: Amgen, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB Pharma, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer. B. Strober: Corporate appointments; B. Strober has been serving as an Editor-in-Chief for the Journal of Psoriasis and Psoriatic Arthritis; and serving as scientific co-director and investigator for CorEvitas Psoriasis Registry. Consultancies; B. Strober has served as a speaker for and/or has received consulting fees and/or honoraria from: AbbVie, Alamar, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim. Shareholder/stock ownership; reports having stock options in Connect Biopharma, Mindera Health. Honoraria; He is also a consultant for Immunic Therapeutics, Kangpu Pharmaceuticals, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, Evelo Biosciences, Incyte, Janssen, Leo, Eli Lilly and Company, Maruho. Grants/research support; He is also a consultant for Meiji Seika Pharma, Mindera Health, Protagonist, Nimbus, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Sanofi-Genzyme, Union Therapeutics, Ventyxbio, vTv Therapeutic. J. Lisse: Consultancies; J. Lisse is employee and stockholder of Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; R. Bolce is employee and stockholder of Eli Lilly and Company. C. Sapin: Shareholder/stock ownership; C. Sapin is employee and stockholder of Eli Lilly and Company. J. Pustizzi: Shareholder/stock ownership; J. Pustizzi is employee and stockholder of Eli Lilly and Company. D. McGonagle: Consultancies; D. McGonagle has received consulting fees and/or honoraria and/or research grants from: AbbVie and Eli Lilly and Company. Grants/research support; His funding sources include or have included the Wellcome Trust-EPSRC, UK NIHR, ARUK, MRC UK and EU FP7 programme.