Interstitial lung diseases (ILD) are a heterogeneous group of fibro-inflammatory disorders that can be progressive despite available therapies. The cornerstones of pharmacologic therapy include immunosuppression and antifibrotics.

Data on the use of rituximab, a B-lymphocyte-depleting monoclonal antibody, often utilized as rescue therapy in progressive and severe ILD, was limited until recently. The RECITAL trial reported the first randomized controlled trial investigating rituximab in severe or progressive autoimmune ILD. Though rituximab was not superior to cyclophosphamide, both agents improved forced vital capacity (FVC) at 24 weeks and respiratory-related quality of life. Rituximab was associated with less adverse events and lower corticosteroid exposure (Maher et al. Lancet Respir Med. 2023;11:45-54). In the DESIRES trial, patients with systemic sclerosis-associated ILD treated with rituximab had preservation of FVC at 24 and 48 weeks compared to placebo (Ebata et al. Lancet Rheumatol. 2021;3:e489-97; Lancet Rheumatol. 2022;4:e546-55). The EVER-ILD investigators compared mycophenolate mofetil (MMF) alone vs addition of rituximab in patients with autoimmune and idiopathic nonspecific interstitial pneumonia (NSIP). Combination therapy was superior to MMF alone in improving FVC and progression-free survival. Combination regimen was well tolerated though nonserious viral and bacterial infections were more frequent (Mankikian et al. Eur Respir J. 2023;61[6]:2202071).

These findings, primarily in autoimmune ILD, are promising and provide clinicians with evidence for utilizing rituximab in patients with severe and progressive ILD. Nonetheless, they highlight the need for additional research and standardized guidance regarding the target population who stands to most benefit from rituximab.