Rituximab combined with intravenous immunoglobulin in autoimmune diseases: a systematic review

Abstract

Background: Although using Rituximab (RTX) and intravenous immunoglobulin (IVIg) alone or sequentially is a well-established treatment for several autoimmune diseases, the combination of these two forms of therapy is still rare, and its use is poorly studied. Aim: To perform a systematic review on the use of RTX associated with IVIG in autoimmune conditions. Methods: PubMed/MEDLINE, EMBASE, and Scielo databases were screened for articles on RTX plus IVIg in autoimmune diseases until May 2024. Results: The review encompassed 21 studies evaluating RTX and IVIg for autoimmune diseases. Ten studies focused on pemphigus, involving 85 patients with diverse subtypes (47 pemphigus vulgaris, 27 pemphigoids, and 11 other variants). Most were case reports or series, with one retrospective study including controls. Positive outcomes were reported across all but one case of paraneoplastic pemphigus. Infections, such as P. jirovecii pneumonia, were noted in three studies, highlighting a potential risk. The other 11 studies involved 24 patients with conditions like polyneuropathies, lupus with CNS involvement, and neuromyelitis optica. While most reported favorable outcomes, one trial on IVIg-dependent polyneuropathies found RTX ineffective in reducing IVIg needs. Adverse events included pneumonia, venous thrombosis with pulmonary embolism, and infusion reactions, demonstrating the need for careful monitoring. Conclusion: RTX plus IVIg seems to be an alternative option for the treatment of refractory autoimmune diseases. However, more studies with a larger number of participants and in different autoimmune diseases are desired.