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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. [ABSTRACT FROM AUTHOR]

Background: Cladribine tablets (CTs) 10 mg, (cumulative dose 3.5 mg/kg [CT3.5] over 2 years) showed efficacy vs placebo in patients with relapsing-remitting multiple sclerosis (RRMS) in the pivotal phase 3 CLARITY study. The CLARITY study included patients treated with 0-2 disease-modifying drugs (DMDs) prior to study entry (patients treated with >2 DMDs prior to study entry were excluded). A total of 433 patients were randomized to CT3.5 and 437 patients to placebo. Objectives: To report clinical outcomes and magnetic resonance imaging (MRI) lesion counts in the subgroup of patients from CLARITY who had used a DMD at any time prior to randomization. Methods: Post hoc analysis of efficacy, annualized relapse rate (ARR), relapse-free rate, MRI activity, and time to 3-month and 6-month confirmed EDSS score progression (CDP) stratified by the cohort of patients who had received a prior DMD treatment before entering the CLARITY study. P values less than 0.05 were considered nominally significant. Results: Of those patients who received a prior DMD (interferon beta [IFNβ]-1a, IFNβ-1b, glatiramer acetate, or natalizumab), 110 were randomized to CT3.5 and 132 received placebo. Among patients with prior DMD use, CT3.5, compared to placebo, resulted in a nominally significant reduction in ARR (CT3.5, 0.22; placebo, 0.42; P < .005), a higher relapse-free rate (CT3.5, 70.4%; placebo, 55.9%; P = .0204), a numerically lower risk of 3-month (hazard ratio = 0.64, P = .1589) and 6-month (hazard ratio = 0.62, P = .2071) CDP, and reductions in the brain lesion counts (P < .001 for each type of lesion). Conclusions: Among patients who were pretreated with either IFNβ-1a, IFNβ-1b, glatiramer acetate, or natalizumab, efficacy outcomes were similar to those seen in the full CLARITY active RRMS population, wherein patients who received CT3.5 showed statistically significant improvements in efficacy outcomes compared to placebo. [ABSTRACT FROM AUTHOR]