Abstract Background CTD-ILD remains a leading cause of morbidity and mortality among patients with systemic autoimmune disorders. Mycophenolate mofetil (MMF) is traditionally a first-line immunosuppressant in this patient population because of its efficacy, safety, and good tolerability. However, some patients still develop progressive fibrosis or recurrent exacerbations despite MMF therapy. Rituximab, an anti-CD20 monoclonal antibody, has emerged as an alternative therapy in CTD-ILD, particularly in those with overlapping inflammatory arthritis features. Real-world comparative data are limited, and the optimal choice or sequence between the two regimens remains unclear. This study compares long-term outcomes between rituximab and MMF in CTD-ILD using a large federated EHR network. Methods We conducted a TriNetX analysis of adults (≥18 y) with interstitial lung disease plus rheumatoid arthritis or systemic sclerosis. Cohort A received rituximab; Cohort B received MMF. Patients with prior lung transplant or prior use of azathioprine, cyclophosphamide, or the alternate study drug were excluded. The index date was the first qualifying drug exposure; outcomes were assessed over 3 years. One-to-one propensity-score matching yielded 1,241 patients per cohort with balanced demographics and key comorbidities. Time-to-event endpoints used Kaplan-Meier methods with log-rank tests and hazard ratios (HRs) with 95% CIs. Results Rituximab was associated with significantly lower all-cause mortality compared with MMF ( HR 0.816, 95% CI 0.676-0.984; log-rank p = 0.033), The risk of respiratory failure was also reduced in the rituximab group (HR 0.718, 95% CI 0.567-0.910; p = 0.006). Although the incidence of new oxygen dependence was lower with rituximab, the difference did not reach statistical significance (HR 0.805, 95% CI 0.610-1.061; p = 0.123). Rates of ICU admission and intubation were comparable between groups (ICU HR 0.800, 95% CI 0.601-1.066; p = 0.127 and intubation HR 0.989, 95% CI 0.641-1.525; p = 0.959). Corticosteroid use did not differ significantly between groups (HR 1.399, 95% CI 0.920-2.127; p = 0.115), suggesting comparable steroid-sparing profiles. Infectious complications occurred at similar rates (HR 0.974, 95% CI 0.762-1.246; p = 0.835). No significant differences were observed in hospitalization (HR 1.134, 95% CI 0.870-1.479; p = 0.352), emergency department visits (HR 1.034, 95% CI 0.784-1.364; p = 0.812), or outpatient visits (HR 1.005, 95% CI 0.539-1.875; p = 0.987). Conclusion In a large propensity-matched CTD-ILD cohort, rituximab showed lower 3-year mortality and respiratory failure risk than MMF, without increased serious infections or critical care needs, supporting its potential as a superior disease-modifying option pending prospective confirmation. This abstract is funded by: none
Khan et al. (Fri,) studied this question.