Risk management plan adherence and clinical outcomes in patients receiving targeted therapies.

backgroundThe expanding use of biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) has substantially improved outcomes in autoimmune diseases but is accompanied by complex safety concerns. Risk management plans (RMPs) have been introduced to mitigate treatment-related risks; however, real-world adherence to these strategies and their broader clinical impact remain incompletely characterized.

methodsWe conducted a retrospective observational cohort study of adult patients with autoimmune diseases who received bDMARDs, tsDMARDs, or biosimilars at a tertiary medical center in southern Taiwan between October 2014 and December 2023. Patients were classified into RMP and non-RMP groups based on completion of predefined pre-treatment safety assessments within 6 months prior to therapy initiation, including pulmonary and tuberculosis evaluation, viral hepatitis screening, and documentation of cardiovascular and malignancy risk factors. Clinical outcomes included Pneumocystis jirovecii pneumonia (PJP), major adverse cardiovascular events (MACE), treatment-related respiratory adverse events, and all-cause mortality. Multivariable logistic regression and time-to-event analyses were performed to evaluate associations between RMP implementation and clinical outcomes.

resultsAmong 1,078 patients included, only 348 (32.3%) fulfilled the predefined RMP criteria prior to treatment initiation. Compared with the RMP group, patients without RMP exhibited significantly higher incidences of PJP (11.9% vs. 2.3%), MACE (8.5% vs. 2.6%), treatment-related respiratory adverse events (50.4% vs. 42.8%), and all-cause mortality (7.3% vs. 1.7%) (all p < 0.05). After multivariable adjustment, RMP implementation remained independently associated with lower risks of PJP (adjusted odds ratio [aOR] 0.18, 95% CI 0.15-0.84), MACE (aOR 0.30, 95% CI 0.13-0.71), and all-cause mortality (aOR 0.21, 95% CI 0.07-0.61). Subgroup and time-to-event analyses demonstrated that anti-CD20 therapy was associated with the highest risk of early-onset PJP, MACE, and mortality, with most events occurring within the first three to six months following treatment. DISCUSSION: In real-world clinical practice, adherence to predefined RMPs prior to targeted therapy initiation is suboptimal and is strongly associated with clinically meaningful differences in infectious, cardiovascular, and survival outcomes. These findings suggest that RMP implementation is associated with benefits extending beyond infection prevention and underscore the importance of standardized, consistently applied risk management strategies, particularly for high-risk targeted therapies such as anti-CD20 agents. Key Points • Adherence to predefined risk management plans (RMPs) before initiating biologic or targeted synthetic DMARDs remains suboptimal in real-world practice. • Implementation of RMPs is associated with lower risks of Pneumocystis jirovecii pneumonia, major adverse cardiovascular events, and all-cause mortality. • Lack of structured pre-treatment safety assessment may contribute to early severe complications after therapy initiation. • Anti-CD20 therapy is associated with a higher risk of early adverse outcomes, underscoring the need for careful risk stratification and monitoring.