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Neurological Sciences

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17.06.2022 | Original Article

Comparative safety of high-efficacy disease-modifying therapies in relapsing–remitting multiple sclerosis: a systematic review and network meta-analysis

verfasst von: Katarzyna Śladowska, Paweł Kawalec, Przemysław Holko, Oktawia Osiecka

Erschienen in: Neurological Sciences | Ausgabe 9/2022

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Abstract

Objective

This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, as well as a potentially high-efficacy DMT, ponesimod, in adult patients with relapsing–remitting multiple sclerosis (RRMS).

Methods

A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included randomized controlled trials (RCTs) with at least 48-week follow-up investigating the use of natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, and ponesimod, as well as other DMTs, in adult patients with RRMS. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The Cochrane Collaboration tool to assess the risk of bias for RCTs was used.

Results

A total of 33 RCTs were included in the systematic review and NMA. A higher rate of adverse events (AEs) was revealed for alemtuzumab versus all other high-efficacy DMTs; for alemtuzumab (average probability of an event: 98.2%) versus placebo (86.2%); for cladribine (3.5 mg; 90.5%) versus ozanimod (1 mg; 84.2%) and placebo; as well as for ocrelizumab (95.5%) versus ozanimod, ofatumumab (88.9%), fingolimod (87.4%), natalizumab (82.8%), and placebo. No significant differences were found between drugs in terms of serious AEs except for cladribine (3.5 mg, 17.3%) versus ocrelizumab (10.3%) and ofatumumab (16.6%) versus ocrelizumab. Significant differences in AEs leading to the discontinuation of study drug were found only for ponesimod (10.1%) versus alemtuzumab (12 mg, 3.0%) and placebo (4.2%). No differences were found in terms of upper respiratory tract infections, nasopharyngitis, fatigue, and nausea between individual high-efficacy DMTs as well as between DMTs and placebo. The results of the NMA indicated a higher risk of infections for alemtuzumab (12 mg) versus ocrelizumab, for cladribine (3.5 mg) versus ofatumumab and placebo, and for ofatumumab versus placebo. For serious infections and urinary tract infections, a significant increase was found only for alemtuzumab (12 mg) versus ocrelizumab, while no differences were found between the other DMTs or between DMTs and placebo. Headache was more common for alemtuzumab (12 mg) as compared with all the other high-efficacy DMTs and placebo, as well as for cladribine versus natalizumab and fingolimod versus natalizumab.

Conclusion

The commonly reported AEs are generally similar among high-efficacy DMTs. However, based on P scores for most analyzed endpoints, natalizumab and ocrelizumab were shown to be the safest DMTs. Considering the limitations of indirect comparisons, further research is needed to confirm our findings, preferably head-to-head RCTs and large observational studies.

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Titel: Comparative safety of high-efficacy disease-modifying therapies in relapsing–remitting multiple sclerosis: a systematic review and network meta-analysis
verfasst von: Katarzyna Śladowska
Paweł Kawalec
Przemysław Holko
Oktawia Osiecka
Publikationsdatum: 17.06.2022
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 9/2022
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06197-3

Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review

Original Article

Sport and migraine—a dynamic relationship

Brief Communication

Myelodysplastic syndrome in an alemtuzumab-treated multiple sclerosis patient

Letter to the Editor

Genetic landscape of early-onset dementia in Hungary

Open Access
Original Article

Experimental animal models of migraine

Short Paper

The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack

Open Access
Review Article

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Neu im Fachgebiet Neurologie

Stumme Schlaganfälle − ein häufiger Nebenbefund im Kopf-CT?

12.01.2025
Computertomografie
Nachrichten

In 4% der in der Notfallambulanz initiierten zerebralen Bildgebung sind „alte“ Schlaganfälle zu erkennen. Gar nicht so selten handelt es sich laut einer aktuellen Studie dabei um unbemerkte Insulte. Bietet sich hier womöglich die Chance auf ein effektives opportunistisches Screening?

CGRP-Antikörper auch bei älteren Migränekranken sicher

09.01.2025
Migräne
Nachrichten

Beginnen ältere Migränekranke eine Prophylaxe mit CGRP-Antikörpern, kommt es anschließend nicht häufiger zu kardiovaskulären Problemen als unter einer Prophylaxe mit Botulinumtoxin. Darauf deutet eine US-Analyse von Medicare-Versicherten.

Frühwarnzeichen für multiple Sklerose bei Kindern und Jugendlichen

09.01.2025
Multiple Sklerose
Nachrichten

Ein Forschungsteam aus Deutschland und Kanada hat eine Reihe metabolischer, okulärer, muskuloskelettaler, gastrointestinaler und kardiovaskulärer Symptome identifiziert, die bei Kindern und Jugendlichen der Diagnose einer multiplen Sklerose (MS) vorausgehen können.

Migräne verstehen und psychotherapeutisch behandeln

31.12.2024
Migräne
Podcast

Das Wissen über die Mechanismen, die im Gehirn bei einer Migräneattacke ablaufen, und mögliche Auslöser wird immer breiter. Der psychologische Psychotherapeut Dr. Dipl.-Psych. Timo Klan fasst den aktuellen Erkenntnisstand zusammen. Und er gibt Tipps für eine differenzierte, individuelle Diagnostik auch von Begleiterkrankungen und beschreibt erfolgreiche psychotherapeutische Interventionen.

Update Neurologie

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Die Leitlinien für Ärztinnen und Ärzte, Arzt und Ärztin unkenntlich diskutieren Gehirn-Scans/© gorodenkoff / Getty Images / iStock (Symbolbild mit Fotomodellen), Senior mit Kopfschmerz/© Motortion / Getty Images / iStock (Symbolbild mit Fotomodell), Kind wird von einer Ärztin befragt/© Monkey Business / Stock.adobe.com (Symbolbild mit Fotomodellen), Springer Medizin Podcast - Migräne/© (M) Foto: goodluz / stock.adobe.com (Symbolbild mit Fotomodell)