Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis

Abstract Background: Systemic sclerosis (SSc) Is a clinically complex and challenging disease, that leads to skin fibrosis. Its most frequent complication is interstitial lung disease (ILD), which leads to a worse prognosis. In this situation, cyclophosphamide is considered the gold standard for its treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. Objectives: This paper objective was to analyze the scientific evidence on the RTX effects on SSc. Methods: A systematic review (SR) was performed including clinical trials (CTs) on the use of RTX in SSc, published up to May 2020. The studies were identified through systematic searches in bibliographic databases using a predefined search strategy. The following databases were used: PUBMED, SCOPUS, SCIELO, LILACS, SCIENCE DIRECT, WEB OF SCIENCE, COCHRANE, WHOLIS, PAHO and EMBASE. Also, a manual search was performed. The methodological quality of the studies was determined using Jadad scale, Risk of Bias Tool (RoB 2.0) and Risk of Bias in Non-Randomized Studies - of Interventions tool (ROBINS-I). A meta-analysis of the randomized CTs was performed, using Review Manager. Results: Ten CTs were included in this SR. Of these, three were randomized and seven were non-randomized. Five showed a statistically significant improvement in forced vital capacity (FVC) at some time during follow-up. Regarding the skin, eight studies showed statistically significant improvements according toa the modified Rodnan skin score. The meta-analysis found positive effects of RTX in SSc, with a statistical significance for lung disease. Conclusion: Rituximab is a promising strategy for the SSc-associated ILD and cutaneous fibrosis treatment. PROSPERO registration number: CRD42019132018.(AU)

Rituximab in systemic sclerosis: A protocol for systematic review.

BACKGROUND: Systemic sclerosis (SSc) is a clinically complex and challenging disease, the most frequent complication of which is interstitial lung disease, which leads to a worse prognosis. In this situation, cyclophosphamide is considered the criterion standard for treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. The objective is to describe a protocol of a systematic review (SR) that analyzes the scientific evidence on the effects of RTX on SSc. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The databases to be searched are PubMed, Scopus, SciELO, LILACS, ScienceDirect, Web of Science, COCHRANE, WHOLIS, PAHO, and EMBASE. The studies that would be included in SR are clinical trials that evaluate the use of RTX in patients with SSc who meet the classification criteria for the disease according to American College of Rheumatology and European League Against Rheumatism (2013) and/or LeRoy criteria will be included in the SR. The data to be extracted are related to the characteristics of the studies: authors, year of publication, study location, type of study, sample size and age, patient characteristics, duration of intervention, therapeutic scheme, follow-up time, main variables, and main results. RESULTS: In our study, we hope to find articles presenting new evidence supporting treatment of SSc with RTX. CONCLUSIONS: The SR will present results of scientific evidence for the effects of RTX in SSc. We hope that the results could strengthen clinical decisions for the best treatment of SSc and guide future researches. PROSPERO REGISTRATION NUMBER: CRD42019132018.