Systematic literature review and network meta-analysis of cladribine tablets versus alternative disease-modifying treatments for relapsing–remitting multiple sclerosis

Abstract

Objective: To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing–remitting multiple sclerosis (RRMS), and in a subgroup with high disease activity (HRA + DAT), using systematic literature review (SLR) and network meta-analysis (NMA).

Methods: MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases were systematically searched to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), no evidence of disease activity (NEDA) and safety.

Results: Of 10,825 articles retrieved and screened, 44 studies assessing 12 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo (p < .05); cladribine tablets were similar or significantly better than other DMT regimens and ranked fourth among DMTs, behind alemtuzumab, natalizumab and ocrelizumab. For CDP for 6 months and NEDA, improvements with cladribine tablets were significantly greater than those of placebo (p < .05), with no comparator DMT demonstrating significantly better results. Similar findings were reported in the HRA + DAT population. Overall adverse event risk for cladribine tablets did not differ significantly from that of placebo and most alternative DMTs.

Conclusion: In this first NMA to consider cladribine tablets, ocrelizumab and daclizumab for treatment of RRMS, cladribine tablets are a comparatively effective and safe alternative to other DMTs in both active RRMS and HRA + DAT populations.

Keywords:

• Cladribine tablets
• disease modifying treatments
• relapsing–remitting multiple sclerosis
• high disease activity
• network meta-analysis
• efficacy
• safety

Transparency

Declaration of funding

This work was supported by Merck KGaA, 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

M.K.S. has disclosed that she/he is an employee of Parexel International, Chandigarh, India. I.S.K. has disclosed that she/he is an employee of Parexel International, Chandigarh, India. S.B. has disclosed that she/he is an employee of Parexel International, London, UK. R.H. has disclosed that she/he has no significant relationships with or financial interests in any commercial companies related to this study or article. G.H. has disclosed that she/he is an employee of Merck KGaA, Middlesex, UK. S.L.W. has disclosed that she/he is an employee of EMD Serono Ltd., Billerica, MA, USA and is also a stock shareholder of EMD Serono, a business of Merck KGaA, Darmstadt, Germany.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

Medical writing support was provided by Mark OConnor and Caroline Spencer of inScience Communications, Springer Healthcare, London, UK, and was supported by Merck KGaA, Darmstadt, Germany.