With recent advances in the understanding of psoriatic disease, it is increasingly considered a systemic inflammatory condition rather than limited to the skin and joints. A variety of biologics are available today for the treatment of psoriasis, but with them, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities differ. We designed an observational, non-interventional, retrospective study of patients with severe psoriasis receiving biologic treatment with IL-17 inhibitors and aimed to investigate the correlations between etiopathogenic factors and the efficacy and persistence of these therapies in a group of psoriasis patients from Romania. Study results show that patients treated with ixekizumab had better persistence and high adherence compared to those treated with secukinumab. In this study, ixekizumab demonstrated lower risks of non-persistence, discontinuation, and switching and a higher likelihood of high adherence compared with secukinumab. This study contributes to the understanding of the persistence of anti-IL17 biologic therapies in psoriasis and the factors that may influence it.