Rituximab in Myasthenia Gravis - Where do we stand?

ABSTRACT

Introduction: Myasthenia gravis (MG) is an antibody-mediated disease with diverse serology and clinical presentation. Currently, MG is managed by untargeted immunomodulatory agents. About 15% patients are refractory to these therapies. Several novel and targeted treatments are on the horizon. Rituximab, a monoclonal antibody, is reported to be highly effective with widespread oof-label usage in MG, particularly in patients with antibody against muscle-specific kinase or refractory disease. However, a recent trial showed negative results. Compared to conventional oral immunosuppressive therapies used in MG, Rituximab has several benefits. Regular hematological monitoring is not required though serious side effects can occur. Current status of Rituximab in MG and newer immunosuppressants is discussed.

Areas explored: Biologic features, clinical effectiveness, safety profile, and newer preparations of Rituximab.

Expert opinion: Rituximab provides a promising option for management of MG, particularly in patients with muscle-specific kinase antibodies or those with refractory disease. Several knowledge gaps remain due to scarcity of data from randomized controlled studies. Despite lack of regulatory approval Rituximab has found widespread usage in MG. Large, well-designed studies are needed to assess the comparative efficacy of Rituximab and its optimal regimen in MG.

KEYWORDS:

• Myasthenia gravis
• acetylcholine receptor
• muscle-specific kinase
• lipoprotein receptor-related protein 4
• IVIG
• biosimilar; autoimmune disease
• immunosuppressant

Article highlights

This box summarizes key points contained in the article.

Multiple novel immunosuppressive therapies with targeted mechanisms of action are on the horizon for MG.

Rituximab is a monoclonal antibody that depletes B-cells and (certain populations of T cells) thereby reducing formation of plasma cells and disease causing antibodies.

Several uncontrolled studies show Rituximab to be safe and effective in MG, particularly in anti-MuSK and refractory MG.

A phase II RCT did not show any significant difference between the steroid sparing effect of Rituximab and placebo. Drawbacks in the trial design and predominant inclusion of patients with mild disease make it difficult to interpret its results.

With availability of cheaper biosimilars and subcutaneous formulations of Rituximab, its off-label usage in MG is likely to increase.

Data from larger controlled studies will be needed for regulatory approval of Rituximab in MG.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.