Rituximab in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis

Abstract

Background: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with rituximab. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through June 2022 for studies using rituximab to treat patients with SSc-ILD. Data Extraction: Disease progression, quality of life, mortality, and adverse event data were extracted. The intervention was rituximab. The standard-of-care comparator group was decided a priori by consensus of the panel as either placebo or mycophenolate. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Three relevant studies were selected. Rituximab significantly improved the forced vital capacity % predicted (mean difference, 3.13; 95% confidence interval [CI], 0.37 to 5.90) and the modified Rodnan Skin Score (mean difference, -7.01; 95% CI, 11.46 to -2.56) at 24-48 weeks. Conclusions: Rituximab use in patients with SSc-ILD is associated with stabilization of lung function. The quality of evidence for study outcomes was considered to be very low, as defined by the GRADE approach. Additional research on treatment with rituximab is imperative.

Keywords: ILD; SSc-ILD; rituximab; systematic review; systemic sclerosis.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.

Figure 2.

Rituximab versus placebo: mean change in FVC % predicted. CI = confidence interval; FVC = forced vital capacity; MD = mean difference; NA = not applicable.*p < 0.05.

Figure 3.

Rituximab versus placebo: mean change in Dl_CO % predicted. CI = confidence interval; Dl_CO = diffusing capacity of the lung for carbon monoxide; MD = mean difference; NA = not applicable.

Figure 4.

Rituximab versus placebo: mean change in mRSS. CI = confidence interval; MD = mean difference; mRSS = modified Rodnan Skin Score; NA = not applicable. *p < 0.05.

Figure 5.

Rituximab versus placebo: mean change in HAQ-DI. CI = confidence interval; HAQ-DI = Health Assessment Questionnaire–Disability Index; MD = mean difference; NA = not applicable. *p < 0.05.