Estimating the comparative efficacy of cladribine tablets versus alternative disease modifying treatments in active relapsing–remitting multiple sclerosis: adjusting for patient characteristics using meta-regression and matching-adjusted indirect treatment comparison approaches

Abstract

Objectives: To estimate the comparative efficacy of cladribine tablets versus alternative disease modifying therapies (DMTs) – fingolimod, natalizumab, alemtuzumab and ocrelizumab – in adults with active relapsing–remitting multiple sclerosis (RRMS), using meta-regression to provide subpopulation-specific estimates of drug effect. Additionally, to determine the feasibility of conducting a matching-adjusted indirect comparison (MAIC) to validate the meta-regression results.

Methods: A published systematic literature review (SLR) identified studies evaluating the efficacy of cladribine tablets and alternative DMTs in the management of active RRMS. A series of meta-regression models were run with adjustment for baseline risk, fitted to data from the intention-to-treat cohorts of trials identified in the SLR. A non-parametric MAIC analysis adjusted for differences between studies by reweighting patient-level data from the index trial to match the mean baseline characteristics reported for trials with only aggregate data.

Results: The meta-regression analysis showed significant overlap in credible intervals for the hazard ratios of 6 month confirmed disability progression (CDP-6M) and annualized relapse rate (ARR), with no therapy statistically dominating in terms of efficacy and all therapies estimated to reduce the ARR compared to placebo in all subpopulations. In the MAIC analysis, cladribine tablets showed a reduction in CDP-6M and ARR comparable to alemtuzumab before and after matching.

Conclusion: This analysis has demonstrated that cladribine tablets have comparable relative efficacy to other highly efficacious DMTs in active RRMS across all subpopulations, thus validating the comparative effectiveness results from previous network meta-analysis. The MAIC analysis showed that cladribine tablets are comparable in efficacy to alemtuzumab in the treatment of patients with RRMS.

Keywords:

• Relapsing–remitting multiple sclerosis
• disease modifying therapy
• cladribine
• meta-regression
• matching-adjusted indirect comparison
• indirect treatment comparison

Correction Statement

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

Note

Transparency

Declaration of funding

This manuscript was funded by EMD Serono Inc., a business of Merck K GaA, Darmstadt, Germany.

Author contributions

All authors were involved in the conception and design of the study. All authors provided analysis and interpretation of the data, critically revised the manuscript for intellectual content and provided final approval of the submitted version.

Declaration of financial/other relationships

A.B., C.T. and M.K.S. have disclosed that they are employees of Parexel International, who acted as a paid health technology consultant to EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany. G.H. has disclosed that he is an employee of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany. S.L.W. has disclosed that she/he is an employee and stock shareholder of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany.

A CMRO peer reviewer on this manuscript declares involvement with CLARITY and CLARITY extension studies and has worked as a consultant for Merck. The other CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors wish to thank Jason Allaire PhD of Generativity Solutions Group for his assistance with editing the paper.

Notes

1 MAVENCLAD is a registered trade mark of Merck KGaA, Darmstadt, Germany.