Burden and determinants of multi-b/tsDMARD failure in psoriatic arthritis

Despite significant therapeutic advances in psoriatic arthritis (PsA), many patients do not achieve remission and cycle through multiple biologic (b)- or targeted synthetic (ts)- DMARDs. Identifying the underlying reasons for repetitive therapeutic failure remains a knowledge gap. Here we describe prescribing patterns and characteristics of PsA patients with multi-b/tsDMARD failure at the NYU Psoriatic Arthritis Center. Nine hundred sixty PsA patients were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype were collected. Multi-b/tsDMARD failure was defined as requiring ≥ 4 b/tsDMARDs. Seven hundred twenty-five patients (75%) used ≥ 1 b/tsDMARD during their disease course. The initial b/tsDMARDs prescribed were predominately anti-TNF agents. 166 (17%) patients had multi-b/tsDMARD failure. Compared to those requiring 1 b/tsDMARD, female sex (OR 2.3; 95%CI 1.4–3.8), axial disease (OR 2.1; 95% CI 1.2–3.6), depression (OR 2.0; 95%CI 1.1–3.7), and obesity (OR 1.7; 95%CI 1.0–2.8) were risk factors for multi-b/tsDMARD failure disease after adjustment for age, disease duration, sex, depression, smoking, obesity, and skin severity. Patients with multi-b/tsDMARD failure PsA also had increased disease activity at their clinical visit (i.e., swollen joint count, p = 0.005). In this cohort, 17% patients with PsA experienced multi-b/tsDMARD failure. These patients were more likely to be female, obese, and have higher rates of axial involvement and depression, along with higher active disease activity. This highlights the inflammatory and non-inflammatory drivers of multiple therapeutic failures, underscoring the need for precision medicine strategies and potential non-pharmacologic adjuvant therapies for patients with PsA to improve outcomes and quality of life.