Treating Autoimmune-Related Interstitial Lung Disease With B Cell Depletion

Abstract

Autoimmune rheumatic diseases may affect vital organs with lung involvement being severe and difficult to treat manifestation. Systemic sclerosis (SSc) commonly affects the lung in the form of interstitial lung disease (ILD). ILD may be also seen in patients with rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), inflammatory myositis (IM), antisynthetase syndrome (AS), and the ANCA-associated vasculitides (AAV). Rituximab (RTX) is an anti-CD20 B lymphocyte depleting mAb, often administered in the treatment of autoimmune rheumatic diseases. Although RTX is an off-label treatment for CTD–ILD, there are numerous reports providing data that is effective in improving both pulmonary function tests (PFTs) and chest computed tomography findings consistent with ILD. There are retrospective uncontrolled studies that assess RTX as a treatment of ILD in autoimmune diseases. These studies, apart from one, do not include patients with AAV-ILD. In SSc-ILD, in particular, there are both controlled and uncontrolled studies displaying encouraging results following B cell depletion. In addition, a number of retrospective uncontrolled studies and fewer prospective studies evaluate RTX in connective tissue diseases CTD–ILD. Although RTX is an approved treatment for AAV there are scarce only data focusing on patients with AAV-ILD specifically. The results of a handful of studies comparing treatment of CTD-ILD with RTX to treatment with other agents are in favor of RTX. Results from large, still ongoing controlled trials are awaited to ascertain RTX effects in ILD encountered in autoimmune rheumatic diseases. We review herein the results of the different RTX trials in patients with autoimmune disease–associated with ILD. Despite the heterogeneity of these studies, RTX may be considered an alternative and safe but still off-label treatment for patients with refractory CTD–ILD.

Interstitial lung disease in patients with anti-neutrophil cytoplasm antibody-associated vasculitis: an update on pathogenesis and treatment

“…Immunosuppression with prednisone and azathioprine has been avoided in UIP-ILD based on the results of the landmark PANTHER-IPF trial conducted in patients with IPF [52]. However, there has been a growing body of evidence supporting the role of immunosuppression, including B-cell-depleting agents such as rituximab, in CTD-ILD [53 ▪ ]. The efficacy of rituximab in CTD-ILD was suggested by a recent meta-analysis [54 ▪ ] and supported by the RECITAL trial [55 ▪▪ ].…”

Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome

“…Rituximab (RTX) seems to be a promising candidate. Throughout the last decade, several studies have assessed the effects of RTX on the treatment of connective tissue disease-related interstitial lung disease (CTDs-ILD) with mostly promising results [6][7][8][9], including two randomized, controlled phase II clinical trials for systemic sclerosis [10,11]. In four recent observational studies, RTX appeared capable of stabilizing or improving ILD in patients with ASS [12][13][14][15].…”

Potential targeted therapy based on deep insight into the relationship between the pulmonary microbiota and immune regulation in lung fibrosis

“…Lastly, During the T H -B interaction, activated T H cells produce cytokines for the B lymphocyte’ s clonal expansion and differentiate into Ab-secreting cells. Therefore, the appropriate T H -B exchange would take a protective effect ( 76 ). However, excessive T H -B exchange may take pathological effects, especially the lung fibrosis possesses persistent severe inflammatory response storm (SIRS) ( 77 ).…”