Rituximab in the Management of Refractory Myasthenia Gravis and Variability of Its Efficacy in Anti-MuSK Positive and Anti-AChR Positive Myasthenia Gravis

Abstract

Myasthenia gravis affects the neuromuscular junction of the skeletal muscles. It results in muscle weakness involving skeletal muscles (diaphragm, extraocular muscles) and myasthenic crisis. Treatment options for myasthenia gravis management have expanded, including azathioprine, corticosteroids, plasma exchange, and tacrolimus. Unfortunately, a few cases of myasthenia gravis don't respond to conventional treatment modalities. Monoclonal antibodies, rituximab (RTX), are novel treatments that have garnered interest as of late due to their efficacy within the patient population presented with refractory form myasthenia gravis. This review aims to showcase how RTX is an effective treatment within different forms of myasthenia gravis. A limited review was performed using databases that include PubMed and Google Scholar. The following keywords were used: "myasthenia gravis," "rituximab," "monoclonal antibody," "anti-AChR antibody," and "refractory myasthenia." The review focused on case reports, human studies, or research surveys based on the inclusion criteria of human studies involving participants more than 18 years of age and published in English literature. Out of 69 articles, 14 were duplicates, and 29 were relevant and met the inclusion criteria. The findings from the study demonstrate that patients with refractory myasthenia gravis responded well to RTX treatment. Furthermore, RTX has been shown to decrease corticosteroid dependence, induce sustained remission, and have a favorable response to anti-MuSK antibody positive myasthenia gravis compared to anti-AChR antibody positive myasthenia gravis. This literature review suggests that patients with refractory myasthenia gravis can benefit from rituximab; however, it has a variable response in different forms of myasthenia gravis.

Knowledge mapping of targeted immunotherapy for myasthenia gravis from 1998 to 2022: A bibliometric analysis

“…Since then, case reports and small-sample studies on RTX treatment in refractory MG have been endlessly streaming ( 55 – 58 ). Although it was not supported by advanced evidence-based medical studies, it has been widely applied in the clinical field, and these studies reflected the effectiveness of RTX in patients with anti-Musk positive and some anti-AChR positive MG ( 59 , 60 ). The second co-cited paper titled “myasthenia gravis” was published by Vincent A ( 38 ), and was published in Lancet in 2001.…”

Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study

“… 24 This may be due to bias in patient selection. RTX also has beneficial effects in refractory MG. 25 In a prospective study by Fatehi et al, 34 patients with refractory MG had significant decreases in Myasthenia Gravis Composite (MGC) and MG-ADL scores after treatment with Zytux, an RTX biosimilar. 26 In a retrospective study with a 10-year follow-up, sustained clinical remission was achieved in all 4 patients with refractory MG after RTX therapy.…”

“…Some authors have suggested that the efficacy of RTX may vary due to different types of antibodies. 23 , 25 In a recent study, the minimum disease state or better was achieved in 72% of MuSK-MG patients after RTX treatment, while this outcome was achieved in only 30% of AChR-MG patients. 23 This finding indicates that RTX may be more effective for MuSK-MG patients than AChR-MG patients.…”

Features of muscle-specific tyrosine kinase autoantibodies and b cells derived from myasthenia gravis patients

“…Anti-CD20-mediated BCDT showed beneficial effects in several autoimmune diseases including multiple sclerosis, pemphigus vulgaris, rheumatoid arthritis, chronic inflammatory demyelinating polyneuropathy (CIDP) and MuSK MG [155][156][157][158][159], whereas no effect of anti-CD20-mediated BCDT therapy could be observed on the titer and clinical outcome in the majority of AChR MG patients [158,160]. Positive effects of anti-CD20-mediated BCDT have been described for severe refractory AChR MG [161,162] and the response seems better at early stages of AChR MG [163]. MG is a very heterogeneous disease [164][165][166][167].…”

“…showing that MuSK MG is a heterogenous disease [162,169]. The efficacy of anti-CD20-mediated BCDT has not been evaluated for MG with autoantibodies targeting LRP4 and agrin yet, while initial promising results showed a beneficial effect of anti-CD20-mediated BCDT in the case of a patient with juvenile seronegative MG [176].…”