Rituximab therapy in severe connective tissue disease associated interstitial lung disease: A retrospective single-centre observational study.

Background: Connective tissue disease-associated interstitial lung disease (CTD-ILD) that progresses despite first-line immunosuppressive therapy is a clinical challenge. Rituximab (RTX) is a chimeric monoclonal antibody targeted to CD20+ B cells, resulting in B-cell depletion, and has been used as a salvage therapeutic modality in severe disease.

Objectives: To investigate the therapeutic effects and safety of RTX in patients with severe CTD-ILD.

Methods: A retrospective observational analysis of patients with severe CTD-ILD treated with salvage RTX therapy and various combinations of immunomodulatory therapy at Wits Donald Gordon Medical Centre, Johannesburg, South Africa, between January 2010 and December 2020 was performed. A total of 19 patients with progressive CTD-ILD, sufficient data, and 24-month follow-up were analysed. The effects of adding salvage RTX to standard drug therapy were investigated with serial pulmonary function testing, high-resolution computed tomography (HRCT) of the chest, and World Health Organization functional class (FC) assessment.

Results: At 24-month follow-up from baseline, there was no significant deterioration in forced vital capacity (0.01 L; 95% CI -0.13 - 0.14) (p=0.91) after commencing RTX salvage therapy. Serial HRCT of the chest showed radiological disease stability or improvement in 13 of the 19 patients (68%). FC assessment showed no significant deterioration compared with baseline (p=0.083). No serious adverse drug reactions or deaths were recorded.

Conclusion: Salvage RTX therapy, in combination with various immunomodulatory treatments, resulted in disease stability in the majority of patients with severe CTD-ILD over a 24-month period.

Study Synopsis: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a challenging clinical entity. Rituximab (RTX), a chimeric monoclonal antibody targeted to CD20+ B cells, resulting in B-cell depletion, has been suggested as a potential therapeutic modality in refractory or severe disease. A single-centre experience of RTX salvage therapy in progressive CTD-ILD is presented. This small study suggests a possible role for RTX therapy in severe or refractory CTD-ILD.