Inflammatory myopathies: shedding light on promising agents and combination therapies in clinical trials

ABSTRACT

Introduction

Due to new insights into the pathogenesis of inflammatory myopathies – in short myositis – and the urgent need for new treatment options in patients who are refractory to standard therapy, multiple novel drugs have been developed and studied in clinical trials. In light of this exciting development, a critical evaluation of the present data is necessary in order to identify the best pathway to future treatment of inflammatory myopathies.

Areas covered

This review focuses on the current evidence from clinical trials in myositis and encompasses dermatomyositis, polymyositis, necrotizing myopathy, antisynthetase-syndrome, overlap myositis, and inclusion body myositis. The results of studies on new therapeutic agents are summarized, in particular larger cohort studies and randomized trials from recent years. When such data were not available, earlier and smaller representative studies were included instead.

Expert opinion

Current studies in most myositis subtypes have shown positive effects of novel biologicals such as abatacept, sifalimumab, JAK-Inhibitors as well as known agents such as rituximab, but further studies are needed to confirm these observations. In inclusion body myositis, the eagerly awaited recent therapeutic trials have missed their primary endpoints, except for the phase 2 study with rapamycin, which has demonstrated significant improvements in secondary endpoints. Future trials will also need to focus on combination therapies of multiple immunomodulatory agents.

KEYWORDS:

• Inflammatory myopathies
• myositis
• clinical trials
• immunosuppressants
• biologicals
• rituximab
• sirolimus

Funding

This paper was not funded.

Acknowledgments

JS, RZ, and SG are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD). RZ and SG are supported by the Deutsche Forschungsgemeinschaft (DFG) within the Clinician Scientist Program “Cell Dynamics in Disease and Therapy” at the University Medical Center Goettingen (project number 413501650). The funding body had no influence in writing the manuscript.

Article highlights

• Following the results from a recent large RCT, IVIg has been approved for treatment of DM

• Larger, controlled trials for the treatment of myositis such as the RIM trial are still scarce

• Smaller studies on the use of novel biological agents including abatacept, sifalimumab and JAK-inhibitors have shown promising effects, but require confirmation by larger, randomized trials

• Therapeutic agents targeting non-inflammatory mechanisms in myositis such as rapamycin are currently under investigation and may have particular impact on the treatment of IBM

• Treatment of IBM remains controversial; standardized outcome measures including valid assessments of dysphagia are needed for future trials in IBM

• Improvement of trial design and the use of standardized response criteria, e.g. IMACS definition of improvement and ACR/EULAR myositis response scale, will benefit the conduction and interpretation of future treatment trials

Reviewer disclosures

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

Declaration of interest

JS has received payments for advisory boards, speaker’s honoraria, travel expenses, or research projects from Alnylam, Argenx, Bayer, Biogen, BioMarin, Biotest, CSL Behring, Grifols, Hormosan, LFB, Novartis, Octapharma, UCB, and Pfizer.

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.