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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

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journal contribution
posted on 29.03.2019 by Andrea Berardi, Mohd Kashif Siddiqui, Catrin Treharne, Gerard Harty, Schiffon L. Wong

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.