Incidence and Predictors of Secondary Failure to Biologic Therapy in Patients with Psoriatic Arthritis

Secondary failure to biologic DMARDs (bDMARDs) is challenging and contributes to the complexity of managing psoriatic arthritis (PsA). We aimed to define the frequency and incidence of this phenomenon in PsA and identify the risk factors for its occurrence. We retrieved data on PsA patients from our single-centre, specialized-care, prospective observational cohort who initiated and remained on bDMARDs for ≥1 year after clinic enrollment between 2000 and 2023. We defined response to therapy at the one-year visit (baseline) as achievement of ≥40% reduction in the swollen joint count (SJC) and either ≥50% reduction in PASI or PASI ≤2. We defined secondary failure as the inability to maintain response criteria or as the clinician's judgment of loss of effectiveness. To examine factors associated with secondary failure, we fitted Cox regression models. Of 482 patients included in the study, 264 (54.8%) were responders at one year. Of these, 94 (35.6%) developed secondary failure at a median of 1.6 [IQR: 0.7, 3.8] years from response. In the multivariable model, higher SJC (HR 1.39, 95% CI 1.05-1.84) and PASI (HR 1.14, 95% CI 1.01-1.29) at baseline were associated with secondary failure. TNFi vs. other bDMARD use (HR 0.39, 95% CI 0.18-0.88), initiation as first-line bDMARD (HR 0.48, 95% CI 0.25-0.91), and treatment initiation during more recent calendar years (HR 0.34, 95% CI 0.12-0.98) were associated with less secondary failure. Secondary failure to bDMARDs is common in PsA and may be influenced by both disease- and therapy-related factors.