Rituximab in severe, treatment-refractory interstitial lung disease

Background and objectiveIn patients with severe interstitial lung disease (ILD) progressing despite conventional immunosuppression, rituximab, a B-lymphocyte depleting monoclonal antibody, may offer an effective rescue therapy. MethodsRetrospective assessment of 50 patients with severe, progressive ILD (of varying aetiologies, excluding idiopathic pulmonary fibrosis (IPF)) treated with rituximab between 2010 and 2012. Change in pulmonary function tests compared with pre-rituximab levels was assessed at 6-12 months post-treatment. ResultsILD was associated with connective tissue disease in 33 patients, hypersensitivity pneumonitis in 6 patients and miscellaneous conditions in 11 patients. At the time of rituximab administration, patients had severe physiologic impairment with a median forced vital capacity (FVC) of 44.0% (24.0-99.0%) and diffusing capacity of carbon monoxide (DLCO) of 24.5% (11.4-67.0%). In contrast with a median decline in FVC of 14.3% and DLCO of 18.8% in the 6-12 months prior to rituximab, analysis of paired pulmonary function data revealed a median improvement in FVC of 6.7% (P<0.01) and stability of DLCO (0% change; P<0.01) in the 6-12 months following rituximab treatment. Two patients developed serious infections (pneumonia) requiring hospitalization following rituximab, and 10 patients died from progression of underlying ILD, a median of 5.1 (1.2-24.5) months after treatment. ConclusionsIn patients with severe, progressive non-IPF ILD unresponsive to conventional immunosuppression, rituximab may offer an effective therapeutic intervention. Future prospective, controlled trials are warranted to validate these findings, and to assess safety outcomes. Interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) progressing despite conventional immunosuppression is often associated with a poor outcome. We report successful rescue therapy with rituximab, a B-cell depleting monoclonal antibody, in a subgroup of patients with progressive ILD despite conventional immunosuppression.