OBJECTIVE: To compare the efficacy and compliance of up-to-date disease modifying therapies (DMTs) in patients with remitting-relapsing MS (RRMS).
METHODS: We searched PubMed, EMBASE and Cochrane Library for eligible studies. Annualized relapse rate, discontinuation due to adverse events (AEs) were assessed as primary outcomes. Sensitivity analysis and inconsistency detection were performed to evaluated whether exclusion of high-risk studies affected the validity. Risk of bias was assessed using Cochrane's Risk-of-Bias Tool 2. Surface under the cumulative ranking curve (SUCRA) was used to estimate the rankings among different DMTs.
RESULTS: 21 studies were included for main report. Seven studies were evaluated as "high risk" and were therefore excluded. Exclusion of high-risk studies did not affect the validity of evidence. The risk of relapses for most DMTs except Betaseron 50 μg was significantly lower comparing to placebo. Incompliance in patients treated with DMTs was not significantly increased comparing to placebo. Dimethyl fumarate and ocrelizumab had superiority in improving MRI outcomes. Ocrelizumab and ofatumumab had the largest reduction of risk in disability progression at 3 months. Referring to SUCRA, ofatumumab, alemtuzumab and natalizumab showed the best efficacy and compliance.
CONCLUSION: The present study demonstrated the hierarchy of DMTs treating RRMS. Ofatumumab, alemtuzumab and natalizumab have superiority with respect to effectiveness and compliance. More studies are required to explore the long-term effect of DMTs. Our findings could provide helpful information and contribute to clinical treatment decision-making.
With the recent successful targeting of B lymphocytes in patients with multiple sclerosis (MS), treatment with anti-CD20 monoclonal antibodies (mAbs) may represent a promising managemental approach, particularly for those with relapsing/remitting MS (RRMS). A network meta-analysis was conducted based on a comprehensive search in Embase, PubMed, and the Cochrane Library to assess the comparative efficacy and safety of currently available anti-CD20 monoclonal antibodies (mAbs), including rituximab, ocrelizumab, and ofatumumab, versus a common comparator (interferon beta-1a [INFβ-1a]) in RRMS patients recruited in randomized clinical trials (RCTs). In a frequentist network meta-analytical model, annualized relapse rates (ARRs) and safety outcomes were expressed as risk ratios (RRs), whereas relapse-free events were expressed as odds ratios (ORs). Treatment ranking was performed using P-scores. The certainty of evidence was appraised using the GRADE approach. Five publications reported the outcomes of seven RCTs (3938 patients, 67.09% females). Compared to INFβ-1a, ocrelizumab reduced the risk of ARR (RR = 0.56, 95% CI, 0.50-0.64), serious adverse events (RR = 0.17, 95% CI, 0.09-0.30), and treatment discontinuation due to adverse events (SAEs, RR = 0.60, 95% CI, 0.39-0.93), and it was associated with higher odds of no relapses (OR = 2.47, 95% CI, 2.00-3.05). Ocrelizumab ranked best among all other treatments in terms of reducing ARR and SAEs. The quality of evidence was low for ocrelizumab, low to moderate for rituximab, and high for ofatumumab. Further large-sized, well-designed RCTs are needed to corroborate the efficacy and safety of ocrelizumab and other anti-CD20 mAbs in RRMS.
Aim: To compare the efficacy of ofatumumab to other disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS). Materials & methods: A network meta-analysis was conducted to determine the relative effect of ofatumumab on annualized relapse rate and confirmed disability progression at 3 months and 6 months. Results: For each outcome, ofatumumab was as effective as other highly efficacious monoclonal antibody DMTs (i.e., alemtuzumab, natalizumab and ocrelizumab). Conclusion: Ofatumumab offers beneficial outcomes for RMS by reducing relapse and disability progression risk.
BACKGROUND: A broad range of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) is available. However, the efficacy and safety of traditional DMTs compared with the recently developed DMTs remain unclear.
OBJECTIVE: Therefore, we have synthesised available evidence of clinical outcomes for DMTs in adults with RRMS.
METHODS: PubMed, Scopus and a manual search were performed. Bayesian network meta-analyses of randomised clinical trials assessing DMTs as monotherapies were conducted. SUCRA and GRADE were used to rank therapies and to assess quality of general evidence, respectively.
RESULTS: Thirty-three studies were included in the meta-analyses. The most effective therapies for the outcome of annualised relapse rate were alemtuzumab (96% probability), natalizumab (96%) and ocrelizumab (85%), compared with all other therapies (hazard ratio versus placebo, 0.31, 0.31 and 0.37, respectively; p < 0.05 for all comparisons) (high-quality evidence). However, no significant differences among these three therapies were found. Discontinuation due to adverse events revealed similarity across all therapies, except for alemtuzumab, which showed less discontinuation when compared with interferon-1a intramuscular (relative risk 0.37; p < 0.05).
CONCLUSION: High-quality evidence shows that alemtuzumab, natalizumab and ocrelizumab present the highest efficacy among DMTs, and other meta-analyses are required regarding adverse events frequency, to better understand the safety of therapies. Based on efficacy profile, guidelines should consider a three-category classification (i.e. high, intermediate and low efficacy).
OBJECTIVE: To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms.
METHODS: Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used.
RESULTS: Twenty Cochrane reviews and an additional 73 full-text articles were selected for data extraction through an updated systematic review (completed November 2016). For people with RRMS, many DMTs are superior to placebo (annualized relapses rates [ARRs], new disease activity [new MRI T2 lesion burden], and in-study disease progression) (see summary and full text publications). For people with RRMS who experienced a relapse on interferon-β (IFN-β) or glatiramer acetate, alemtuzumab is more effective than IFN-β-1a 44 μg subcutaneous 3 times per week in reducing the ARR. For people with primary progressive MS, ocrelizumab is probably more effective than placebo (in-study disease progression). DMTs for MS have varying adverse effects. In people with CIS, glatiramer acetate and IFN-β-1a subcutaneous 3 times per week are more effective than placebo in decreasing risk of conversion to MS. Cladribine, immunoglobulins, IFN-β-1a 30 μg intramuscular weekly, IFN-β-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS. Suggestions for future research include studies considering comparative effectiveness, usefulness of high-efficacy treatment vs stepped-care protocols, and research into predictive biomarkers.
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 < 0.05); 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 < 0.05), 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.
To compare the efficacy and compliance of up-to-date disease modifying therapies (DMTs) in patients with remitting-relapsing MS (RRMS).
METHODS:
We searched PubMed, EMBASE and Cochrane Library for eligible studies. Annualized relapse rate, discontinuation due to adverse events (AEs) were assessed as primary outcomes. Sensitivity analysis and inconsistency detection were performed to evaluated whether exclusion of high-risk studies affected the validity. Risk of bias was assessed using Cochrane's Risk-of-Bias Tool 2. Surface under the cumulative ranking curve (SUCRA) was used to estimate the rankings among different DMTs.
RESULTS:
21 studies were included for main report. Seven studies were evaluated as "high risk" and were therefore excluded. Exclusion of high-risk studies did not affect the validity of evidence. The risk of relapses for most DMTs except Betaseron 50 μg was significantly lower comparing to placebo. Incompliance in patients treated with DMTs was not significantly increased comparing to placebo. Dimethyl fumarate and ocrelizumab had superiority in improving MRI outcomes. Ocrelizumab and ofatumumab had the largest reduction of risk in disability progression at 3 months. Referring to SUCRA, ofatumumab, alemtuzumab and natalizumab showed the best efficacy and compliance.
CONCLUSION:
The present study demonstrated the hierarchy of DMTs treating RRMS. Ofatumumab, alemtuzumab and natalizumab have superiority with respect to effectiveness and compliance. More studies are required to explore the long-term effect of DMTs. Our findings could provide helpful information and contribute to clinical treatment decision-making.
