Background/Purpose: The management of patients with psoriasis and psoriatic artrhitis (PsA) has been recently enriched and has thus become more challenging by the wide armamentarium of treatments, especially biologics (bDMARD) without reliable predictors of response. We herein investigated the features of patients with PsA which may be associated with the failure of one or more bDMARDs in the real-world practice.

Methods: We retrospectively collected data of patients ≥ 18 years with PsA attending the Rheumatology outpatients Clinic at Humanitas Research Hospital between February 1^st 2020 and March 1^st 2022. For each patient we collected demographic, laboratory and clinical information considering all domains involved in the course of the disease and concomitant comorbidities. T-test, Mann- Whitney, and chi-square test were used to compare data among soubgroups. Logistic regression models analyzed the impact of patients characteristics on therapeutic failures, adjusted for confounders.

Results: Our analysis was performed on 319 patients (45% men) with PsA fulfilling the CASPAR criteria, including 161 patients (52%) who failed a first-line bDMARD, 74 patients (24%) who failed a second-line bDMARD and 69 who failed more than 2 bDMARDs (18%).

Failure of at least one bDMARD correlated with female gender (p=0.002), age between 60 and 80 years old (p=0.02), concomitant glucocorticoids use (p=0.001), coexisting neurological disease (p=0.042) and history of cancer (p=0.017) or recurrent infections (p=0.03). The multivariate analysis confirmed male sex as protective towards bDMARDs failure (OR 0.5, 95% CI 0.32 – 0.78; p=0.002) regardless of age, but the highest risk was found in patients aged 60 to 80 years (OR 2.17, 95% CI 0.98-4.77; p=0.05). When the analysis included only patients failing a TNF inhibitor, besides male gender and age, fibromyalgia (p=0.012) and NSAIDs use (p=0.03) were associated with treatment failure while at multivariate analysis male gender (OR 0.57, 95% CI 0.33-0.99; p=0.047) and the use of NSAIDs (OR 2.01, 95% CI 1.79-11.55; p=0.001) were associated with a lower risk of treatment failures. When the analysis was performed only in patients failing an IL-17 inhibitor, no significant correlation was found, but most patients (62%) were at least on their second bDMARD. In patients failing ≥3 biologics, we observed a correlation of the multifailure status with depression (OR 2.54, 95% CI 0.93-6.95; p=0.069), but without significant differences at the multivariate except for the use of glucocorticoids (OR 5.05, 95% CI 2.08-12.23; p< 0.001). Since gender consistently influenced treatment outcomes, we analysed baseline differences and observed that men have more frequently psoriasis (p=0.038), interstial lung disease (p=0.014), hypertension (p=0.01) and diabetes (p=0.027) and less frequently enthesitis (p< 0.0001), neurological diseases (p=0.007), recurrent infections (p=0.003), thyroiditis (p=0.016), fibromyalgia (p< 0.0001) and use of glucocorticoids (p=0.004).

Conclusion: Depression and other neurological disorders, along with female gender, older age and other comorbidities, are associated with higher risk of failing one or more bDMARDs, particularly TNF inhibitors, in real-world practice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depression-and-other-neurological-disorders-are-associated-with-biologic-dmard-failure-in-psoriatic-arthritis/