Association of Rituximab with Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients with Pemphigus

Importance: The association of different therapeutic approaches with long-term cardiovascular and metabolic outcomes in patients with pemphigus remains to be precisely evaluated. Objective: To assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab compared with those receiving treatment with first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]). Design, Setting, and Participants: A global population-based retrospective cohort study compared 961 patients with pemphigus that was managed with rituximab with those treated with azathioprine or MMF (n = 961) regarding the risk of several cardiovascular and metabolic outcomes. Propensity score matching was performed to optimize comparability. Patients were enrolled from the Global Collaborative Network of TriNetX platform. Main Outcomes and Measures: Risk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis. Results: Of 1602 participants, 855 (53.4%) were women and 747 (46.6%) were men; the mean (SD) age was 54.8 (16.6) years for those treated with rituximab and 54.4 (18.2) years for those treated with azathioprine or MMF. Compared with those treated by azathioprine/MMF, patients treated with rituximab experienced a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P =.01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P <.001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P =.003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P <.001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P <.001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P <.001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P <.001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P <.001). The all-cause mortality was comparable between patients in both groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P =.77). Conclusions and Relevance: The results of this cohort study suggest that rituximab was associated with protection against long-term cardiovascular and metabolic outcomes compared with conventional immunosuppressants. This agent might be particularly preferred in individuals with preexisting cardiovascular and metabolic risk factors.