A39-26 Use of Rituximab in Interstitial Lung Diseases Beyond Traditional Indications: Real-world Experience From a Tertiary ILD Center

Abstract Background Rituximab, a monoclonal antibody targeting CD20-positive B cells, is FDA-approved for treating moderately to severely active rheumatoid arthritis in adults with inadequate response to one or more TNF antagonists.1 Beyond rheumatoid arthritis, it is used for systemic autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren’s syndrome, and idiopathic inflammatory myopathies (IIM), such as antisynthetase syndrome (ASS).2-4 In pulmonary medicine, rituximab is increasingly used for connective-tissue-disease-associated ILD (CTD-ILD) and pulmonary vasculitides when conventional immunosuppressants are ineffective or poorly tolerated. Evidence for non-traditional ILD indications, including ILD without a defined autoimmune substrate, is limited. We aimed to characterize clinical outcomes, safety, and one-year survival among rituximab-treated patients with non-traditional ILD compared with CTD-ILD or vasculitis. Methods Patients with any ILD subtype receiving rituximab at the Cleveland-Clinic Respiratory Institute between 2013-2024 were included. Data were abstracted from electronic medical records, with each chart reviewed for up to five ILD diagnoses. Patients with CTD-ILD or pulmonary vasculitis—including antisynthetase syndrome, systemic sclerosis, polymyositis/dermatomyositis, rheumatoid-arthritis-associated ILD, Sjögren’s, SLE, GPA, MPA, or EGPA—were classified as traditional indications. Others—including fibrotic hypersensitivity pneumonitis, unclassifiable fibrosis, GLILD, organizing pneumonia, sarcoidosis, or post-infectious fibrosis—were non-traditional. Clinical status (improved, unchanged, worsened) and adverse events (AEs: infections, infusion reactions, malignancy, hospitalizations) were assessed at the first two post-infusion visits. Vital status, lung transplantation, and one-year outcomes were recorded. Results Among 270 patients, 180 (67%) had traditional indications and 90 (33%) non-traditional. Common non-traditional diagnoses included nonspecific interstitial pneumonia (28%), fibrotic hypersensitivity pneumonitis (19%), interstitial pneumonia with autoimmune features (12%), and post-infectious fibrosis (11%). At first follow-up (median 2.3 months), improvement was observed in 59% of traditional and 46% of non-traditional patients; at six months, 56% and 37%, respectively. AEs occurred in 12% and 6% initially, 8% and 1% at the second visit, mainly mild infusion reactions or infections. Hospitalizations (22% vs 15%) and deaths (12% vs 4%) were higher among non-traditional ILD. At one year, 173 (64%) improved, 54 (20%) worsened, 34 (13%) experienced an AE, and 71 (26%) were hospitalized. Thirty-seven (13.7%) died, and 12 (4.4%) underwent lung transplantation. Conclusions In this real-world ILD cohort, most rituximab-treated patients improved or remained stable within six months. Adverse events were infrequent, and two-thirds demonstrated clinical improvement within the first year. Hospitalizations and deaths were concentrated among non-traditional ILD patients. These findings support rituximab as a safe, well-tolerated immunomodulatory option for progressive or refractory ILD and provide benchmark safety and efficacy data for future studies. This abstract is funded by: None