Rituximab rescue therapy in severe, progressive interstitial lung disease

Aims: In a subgroup of interstitial lung diseases (ILDs), immune-mediated pulmonary inflammation is a key pathobiologic process in disease initiation and progression. If untreated, pulmonary inflammation may progress to irreversible fibrosis, and eventually respiratory failure and death. In many ILDs other than idiopathic pulmonary fibrosis, immunosuppressive therapy (including IV cyclophosphamide) may be required to prevent progression of the inflammatory/fibrotic process. Rituximab, a chimeric monoclonal antibody, results in rapid B cell depletion from the peripheral circulation, and has proven to be an effective therapy in a number of immune-mediated conditions.

Aims: To retrospectively assess the effect of rituximab in patients attending the Royal Brompton Hospital ILD Unit, with severe, progressive ILD (non-IPF), refractory to conventional immunosuppression.

Methods: Review of our pharmacy-prescribing database identified 50 patients with severe, progressive ILD (35 with connective tissue-disease-associated ILD; five with fibrotic hypersensitivity pneumonitis, two with desquamative interstitial pneumonitis and five with miscellaneous/undefined entities) who received treatment with rituximab between 2007–2012. All patients had failed to respond to conventional immunosuppression (IV cyclophosphamide n=41; IV methylprednisolone n=4; azathioprine or mycophenolate n=5) prior to rituximab administration. Pre-treatment and follow-up pulmonary function tests, serum immunoglobulin levels, lymphocyte subsets, and survival data were collected. Lung function and/or survival status were available for all patients for at least six months following Rituximab treatment; lung function data at one year post-Rituximab was available for 38 patients.

Results: 50 patients (31 women) received treatment with rituximab. At the time of treatment, mean DLCO was 25.8% (±10.2) and mean FVC was 51.5% (±16.9). In the 12 months prior to rituximab, there had been a significant average decline in DLco by –24% (±17) (p=<0.01) and in FVC by –19% (±13) (p=0.03). In the 38 patients with full lung function data available at one year following Rituximab, a mean improvement in DLco by 12%(±7) (p=0.04) was observed, while FVC remained stable. Four patients developed infectious complications requiring iv antibiotics. There were six deaths in the year following Rituximab treatment, associated with disease progression.

Conclusions: Rituximab may be an effective rescue therapy in patients with severe, progressive ILD associated with pulmonary inflammation. Future prospective, controlled trials are warranted to validate these findings.