Rituximab in the treatment of systemic sclerosis–related interstitial lung disease: a systematic review and meta-analysis

Abstract

Objectives To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. Methods PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. Results A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). Conclusions Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

“…Our data support previous studies reporting that B-cell depletion positively impacts lung and skin outcomes in patients with SSc [30][31][32][33][34]. Interestingly, if compared to other available studies, our experience is supported by a longer-term follow-up.…”

Multiple Manifestations of Systemic Sclerosis Affect Walk Distance

“…Rituximab (RTX) is an immunomodulatory drug that can inhibit ILD progression in SSc. This effect is not limited to patients with moderate or severe disease but has also been reported in subjects with mild ILD ( 5 ). Further characterization of pulmonary function of the study participants, including FVC% predicted and its response to treatment, would have been informative in Table 1 as well as Tables E2–7.0 in the work by Zamanian and colleagues.…”

“…ILD affects 25–90% of patients with SSc and may precede or develop in parallel with PAH ( 5 ). In this study, although subjects with a TLC <70% predicted were excluded, patients with mild fibrosis on high-resolution computed tomography were eligible to participate.…”

“…The 6MWD is a composite outcome measure to which pulmonary vascular function is only one out of multiple contributing factors ( 3 , 4 ). Given the systemic nature of this disease ( 5 , 6 ) and our current knowledge on RTX in rheumatology, we ask the authors to elaborate on changes in measures of ILD, arthritis, and myopathy over the course of the study.…”

The target on B cells in Systemic Sclerosis: a “midsummer dream” to extinguish inflammation and prevent early disease progression to fibrosis

“…Currently available therapeutic strategies could target both inflammatory pathways (with anti-CD20 Rituximab and/or mycophenolate mofetil or anti-IL6 tocilizumab), and pro-fibrotic pathways (with nintedanib), to extinguish inflammation and to prevent early disease progression to fibrosis data obtained by the EUSTAR registry [28,29]. The same results have been also obtained with RTX biosimilars [30], and are supported by two meta-analyses [31,32].…”