Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials

BackgroundRelapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the cli...

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Main Authors: Eoin Moloney, Atefeh Mashayekhi, Sakshi Sharma, Vasileios Kontogiannis, Amir Ansaripour, Wallace Brownlee, David Paling, Mehdi Javanbakht
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2024.1479476/full
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author Eoin Moloney
Atefeh Mashayekhi
Sakshi Sharma
Vasileios Kontogiannis
Amir Ansaripour
Wallace Brownlee
Wallace Brownlee
David Paling
Mehdi Javanbakht
author_facet Eoin Moloney
Atefeh Mashayekhi
Sakshi Sharma
Vasileios Kontogiannis
Amir Ansaripour
Wallace Brownlee
Wallace Brownlee
David Paling
Mehdi Javanbakht
author_sort Eoin Moloney
collection DOAJ
description BackgroundRelapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).MethodsThe SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).ResultsWe included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64–1.62)), natalizumab (RR 0.99 (0.59–1.65)), alemtuzumab (RR 0.86 (0.51–1.46)), and ocrelizumab (RR 0.75 (0.44–1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49–1.92)), natalizumab (HR 1.13 (0.53–2.40)), alemtuzumab (HR 1.25 (0.56–2.81)), and ocrelizumab (HR 1.29 (0.57–2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.ConclusionsResults of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.
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spelling doaj-art-df651370b4b1480a860a74e4d92fbec22024-12-06T05:10:06ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-12-011510.3389/fneur.2024.14794761479476Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trialsEoin Moloney0Atefeh Mashayekhi1Sakshi Sharma2Vasileios Kontogiannis3Amir Ansaripour4Wallace Brownlee5Wallace Brownlee6David Paling7Mehdi Javanbakht8Optimax Access Ltd, Southampton, United KingdomOptimax Access Ltd, Southampton, United KingdomOptimax Access Ltd, Southampton, United KingdomOptimax Access Ltd, Southampton, United KingdomOptimax Access Ltd, Rotterdam, NetherlandsQueen Square MS Centre, UCL Queen Square Institute of Neurology, London, United KingdomNIHR University College London Hospitals Biomedical Research Centre, London, United KingdomDepartment of Neurology, Royal Hallamshire Hospital Sheffield, Sheffield, United KingdomOptimax Access Ltd, Southampton, United KingdomBackgroundRelapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).MethodsThe SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).ResultsWe included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64–1.62)), natalizumab (RR 0.99 (0.59–1.65)), alemtuzumab (RR 0.86 (0.51–1.46)), and ocrelizumab (RR 0.75 (0.44–1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49–1.92)), natalizumab (HR 1.13 (0.53–2.40)), alemtuzumab (HR 1.25 (0.56–2.81)), and ocrelizumab (HR 1.29 (0.57–2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.ConclusionsResults of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.https://www.frontiersin.org/articles/10.3389/fneur.2024.1479476/fullrelapsing multiple sclerosisrelapsing-remittingsecondary progressivemonoclonal antibodiesublituximabsystematic review
spellingShingle Eoin Moloney
Atefeh Mashayekhi
Sakshi Sharma
Vasileios Kontogiannis
Amir Ansaripour
Wallace Brownlee
Wallace Brownlee
David Paling
Mehdi Javanbakht
Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
Frontiers in Neurology
relapsing multiple sclerosis
relapsing-remitting
secondary progressive
monoclonal antibodies
ublituximab
systematic review
title Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
title_full Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
title_fullStr Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
title_full_unstemmed Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
title_short Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
title_sort comparative efficacy and tolerability of ublituximab vs other monoclonal antibodies in the treatment of relapsing multiple sclerosis a systematic review and network meta analysis of randomized trials
topic relapsing multiple sclerosis
relapsing-remitting
secondary progressive
monoclonal antibodies
ublituximab
systematic review
url https://www.frontiersin.org/articles/10.3389/fneur.2024.1479476/full
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