Introduction: We aimed to investigate the clinical, immunological, and genetic factors affecting the response to anti-TNF alpha (tumor necrosis factor-alpha) and interleukin-12/23 therapies and drug survivals. Methods: A total of 180 patients were divided into two groups: 89 patients who used at least two biologic agents, with the initial biologic agent used less than 12 months (group A), and 91 biologic-naive patients who have been receiving a single biologic agent for more than 12 months (group B). ELISA (enzyme-linked immunosorbent assay) was used to analyze anti-drug antibodies (ADAs) in blood samples. Clinical data of the patients were retrospectively analyzed. HLA-SSO (sequence-specific oligonucleotide) Typing Kits were used for HLA-C typing. IBM SPSS v.21 was used for statistical analysis. Results: Infliximab had the longest drug survival as the first biologic agent in group A (p = .015). Etanercept had the lowest ADA count compared to the other anti-TNF agents (p = .001). HLA-Cw6 negativity, late-onset psoriasis, smoking and alcohol use were determined to be risk factors for treatment failure in group A. HLA-Cw6 was found to be associated with type I psoriasis (p = .000). Conclusions: Although our study is retrospective of a relatively low number of patients, this is a preliminary study focusing on two different patient populations based on therapy response.