Objective: To investigate the influence of comorbidities on treatment response, disease activity and persistence with first-line IL-17 inhibitor (IL-17i) treatment in patients with PsA. Methods: Patients were divided into three groups depending on the presence and/or severity of comorbidities using the Charlson Comorbidity Index (CCI). Groups were CCI 0: no comorbidities, CCI 1: one comorbidity and CCI ≥2: two or more comorbidities or one or more severe comorbidities. Outcomes in the groups were compared for treatment persistence, treatment response and disease activity. Results: A higher CCI score was associated to an elevation in baseline CRP, swollen joint count and frequency of depression and/or anxiety. The median drug persistence in the groups were CCI 0: 1.8 years, CCI 1: 1.9 years and CCI ≥2: 1.5 years, but was not statistically significant to the CCI score. There were no significant differences in clinical response rates between the groups. Conclusion: The presence of comorbidities was associated with increased baseline disease activity and frequency of depression and/or anxiety, but was not associated with shorter treatment persistence or lower clinical response rates in a cohort of 155 Danish patients with PsA treated with first-line IL-17i.