Conventional and emerging treatments and controversies in myasthenia gravis

ABSTRACT

Introduction

Myasthenia gravis (MG) is caused by IgG antibodies against different proteins at the neuromuscular junction. Anti-acetylcholine receptor (AChR) Abs are detected in the great majority of patients. MG management consists of long-term immunotherapy, based on steroids and immunosuppressants, short-term treatments and therapeutic thymectomy. Targeted immunotherapies that reduce B cell survival, inhibit complement activation, and decrease serum IgG concentration have been evaluated in trials and have entered clinical practice.

Areas covered

Herein, the efficacy and safety data of conventional and novel therapeutic options are reviewed and their indications in the disease subtypes are discussed.

Expert opinion

Even though conventional treatment is generally effective, 10–15% of patients have refractory disease and there are safety concerns related to long-term immunosuppression. Novel therapeutic options offer several advantages but also have limitations. Safety data based on long-term treatment are not yet available for some of these agents. The mechanisms of action of new drugs and the immunopathogenesis of different MG subtypes must be considered in therapy decision making. Integrating new agents in the treatment scenario of MG can significantly improve disease management.

KEYWORDS:

• Myasthenia gravis
• immunosuppressive therapy
• complement inhibitors
• FcRn blockers
• B cell targeting agents

Article highlights

• Myasthenia gravis (MG) is a heterogeneous disease, including subtypes with distinct antibodies and immunopathogenic mechanisms.

• Even though conventional treatment is generally effective, 10-15% of patients have refractory disease; there are also safety concerns related to long-term immunosuppression.

• Patient subgrouping through antibody detection is crucial when planning treatment, especially with novel agents with targeted effects on the immune system.

• Complement inhibitors and blockers of the FcRn are fast-acting agents that may be used in treating MG deterioration phases. Rituximab is a disease-modifying therapy for MG with antibodies to MuSK.

• New therapeutic options offer several advantages including more selective effects on the immune system and a relatively good safety profile.

Declaration of interest

A Evoli is on the scientific award jury for Grifols. She is also on the advisory board of UCB Pharma, Alexion and Argenx. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.