Mavrilimumab: a unique insight and update on the current status in the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease, which affects joints and extra-articular structures. Nowadays, the armamentarium of therapeutic options is progressively expanding and embraces several mechanisms of action: TNF inhibition, B-cell depletion, T-cell co-stimulation inhibition, IL-6 blockade, and JAK-inhibition. Granulocyte-Monocyte-Colony-Stimulating-Factor (GM-CSF) is a mediator acting as a cytokine with a proven pathogenetic role in RA, providing a potential alternative target for the management of the disease. Mavrilimumab is a monoclonal antibody against GM-CSF receptor, which has been successfully tested in RA patients.

Areas covered: Beginning with a description of the preclinical evidence and the rationale for GM-CSF blockade in RA, this review will provide a wide overview of mavrilimumab efficacy and safety profile by analyzing phase I/II RCTs conducted in patients with moderate to severe RA.

Expert opinion: According to the promising results from phase I-II RCTs, mavrilimumab could be considered as an additional therapeutic option for RA patients multi-resistant to the available targeted drugs. However, the optimal dose and the profile of this new drug should be confirmed in phase III RCTs before the marketing.

Trial registration: ClinicalTrials.gov identifier: NCT01706926.

Trial registration: ClinicalTrials.gov identifier: NCT01715896.

Trial registration: ClinicalTrials.gov identifier: NCT01712399.

Trial registration: ClinicalTrials.gov identifier: NCT00771420.

Trial registration: ClinicalTrials.gov identifier: NCT01050998.

KEYWORDS:

• Biologic agents
• efficacy
• Granulocyte-macrophage colony-stimulating factor
• mavrilimumab
• rheumatoid arthritis
• safety

Article highlights

• The increasing number of available therapeutic options has dramatically improved the treatment of rheumatoid arthritis (RA), but the variety and the complexity of RA pathogenetic mechanisms still limit the proportion of patients achieving clinical remission, suggesting the need for the identification of novel mechanisms of action.

• Besides its well-known hematopoietic role, Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine involved in the differentiation, polarization and activation of immune cells as macrophages, dendritic cells, and lymphocytes, resulting in a strong effect on the immune/inflammatory cascade of RA.

• The available data on the use of the first anti-GM-CSF agent mavrilimumab for RA are encouraging and warrant phase III trials, in order to better establish the future positioning of this novel drug in the therapeutic algorithm of RA.

This box summarizes key points contained in the article.

Box 1. Drug summary

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

Additional information

Funding

This paper was not funded.