Quantitative evaluation of drug efficacy in the treatment of myasthenia gravis

ABSTRACT

Objectives

This study aimed to quantitatively evaluate placebo effect and drug efficacy characteristics and identify associated factors that affect quantitative myasthenia gravis (MG) score (QMGs) and MG activities of daily living score (MG-ADLs) in patients with MG.

Methods

Randomized placebo-controlled clinical trials were comprehensively searched in public databases (PubMed, EMBASE, and Cochrane Library databases).

A model-based meta-analysis was developed to describe time-course about drug efficacy and placebo effect.

Results

Twelve articles including 13 trials (673 participants) that were eligible for this study evaluated four immunosuppressants (tacrolimus, cyclosporine, prednisone, and mycophenolate mofetil) and five targeted therapy drugs (eculizumab, belimumab, zilucoplan, efgartigimod, and iscalimab). The pharmacodynamic model showed that eculizumab had the highest efficacy in reducing QMGs scores (3.66 points), and efgartigimod had the highest efficacy in reducing MG-ADLs scores (1.97 points). The placebo effect of QMGs and MG-ADLs increased apparently with time and reached 52% and 90% of their maximum effect in 12 weeks, respectively. In addition, this study found that the activities of daily living ability increased with the increase of the proportion of patients undergoing thymectomy.

Conclusion

This study analyzed the efficacy characteristics of nine drugs. The present findings provide necessary quantitative information for drug development of MG.

KEYWORDS:

• Efficacy
• model-based meta-analysis
• myasthenia gravis activities of daily living
• Myasthenia Gravis
• placebo
• quantitative myasthenia gravis score

Supplementary material

Supplemental data for this article can be accessed here.

Acknowledgments

We thank all staff of the center for drug of clinical research, Shanghai University of Traditional Chinese Medicine.

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.

Author contributions

Rui Chen: Software, Writing - original draft. Ningyuan Zhang:Validation. Lili Gao: Visualization. Ying Zhong: Data curation. Ling Xu: Investigation. Hongxia Liu: Supervision. Qingshan Zheng: Writing -review & editing. Lujin Li: Writing - review & editing.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the National Major S&T Project [2018ZX09734005, 2018ZX10303501, 2018ZX09731016, 2017ZX09304003 and 2018ZX09711001-009-011], the project of Shanghai Municipal Health Planning Commission [2018YQ48], and Shanghai S&T Innovation Plan [17401970900].