Background: Primary failure of advanced therapy (biologic and targeted synthetic disease-modifying anti-rheumatic drugs [DMARDs]) is not infrequent in rheumatologic practice. 

Objective: In this study, we aimed to define the incidence of primary failure of advanced therapy in patients with psoriatic arthritis (PsA) and identify the factors associated with its development.

Methods: We retrieved data from patients enrolled in our prospective observational PsA cohort between 2000 and 2023. We included only patients commencing treatment with advanced therapy (not necessarily the first-ever) after clinic enrollment. We defined primary failure as the physician’s judgment of inefficacy during the first year of therapy, or failure to achieve ≥40% reduction in the baseline swollen joint count (baseline refers to the visit just before the commencement of therapy) and ≥50% reduction in the baseline Psoriasis Area and Severity Index. We identified patients with primary failure and compared them to responders and to patients who stopped treatment for non-efficacy-related reasons (side effects, pregnancy, expense, or personal preference). We used univariate and multivariate multinomial logistic regression to model the effects of each variable on the outcome.

Results: 591 patients on advanced therapy were included in the study, with a mean (standard deviation) age of 48.2 (13.0) years; 329 (55.7%) were males. Tumor necrosis factor inhibitors (TNFi) were the most used advanced therapy (486 [82.2%] patients); 232 (39.3%) were on etanercept. Interleukin-17 inhibitors (IL-17i), IL-23i (and IL-12/IL-23i), and targeted synthetic DMARDs were prescribed to 49 (8.3%), 26 (4.4%), and 30 (5.1%) patients, respectively. Most of the medications were used as the first-ever advanced therapy (81.2%).  

209 (35.4%) patients experienced primary failure, with an incidence rate of 0.35 per person-year. In the multivariate regression model (Table 1), the following variables were associated with primary failure: daily alcohol consumption (odds ratio [OR] 3.52, 95% confidence interval [CI] [1.33, 9.31]), higher body mass index (OR 1.04, 95% CI [1.01, 1.08]), and fibromyalgia (OR 2.07, 95 % CI [1.03, 4.16]). Higher educational level (OR 0.51, 95% CI [0.38, 0.87]), a higher damaged joint count (OR 0.95, 95% CI [0.93, 0.99]), and HLA-B*27 positivity (OR 0.40, 95% CI [0.17, 0.97]) were associated with a reduced risk of primary failure. 

Conclusion: Primary failure of advanced therapy is common in PsA and may be influenced by several factors, including socioeconomic characteristics, comorbidities, and disease-related features.