Comparative Efficacy of 35 Disease-modifying Therapies in Relapsing-remitting MS: A Network Meta-analysis Identifying Top Performers for Relapse, MRI Activity, and Disability Progression
Mohamed Mamdouh1, Ahmed Hashem Fathallah2, Ibrahim Kamal3, Mohamed Nabil Galal4, Mohamed Nasser Elshabrawi5, Abdulrahman Ahmed Albalasy6, John Magdy Daniel Isaac7, Omar F Abbas3, Esraa Ragaey1, Hossam Tharwat Ali8, Dalia Atef Abouda9, Mahmoud Ahmed Rabea1, Mohamed Nabil Nady1
1Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt, 2Faculty of Medicine, Minya University, Minya, Egypt, 3Faculty of Medicine, Al-Azhar University, Cairo, Egypt, 4Faculty of Medicine, Menoufia University, Menoufia, Egypt., 5Faculty of medicine Port Siad University Port SaidEgypt, 6Faculty of Medicine, Kafr Elsheikh University, Egypt, 7Faculty of Medicine, Menoufia University, Menoufia, Egypt, 8Qena Faculty of Medicine, South Valley University, Qena, Egypt, 9Faculty of medicine, Alexandria university, Alexandria, Egypt
Objective:
This network meta-analysis evaluates the comparative efficacy of 35 DMTs in addressing relapses, reducing radiological burden, and mitigating disability progression.
Background:
Relapsing-remitting multiple sclerosis (RR-MS) is an immune-mediated inflammatory demyelinating disease. The broad spectrum of disease-modifying therapies (DMTs) reflects a trajectory toward personalized treatment.
Design/Methods:
A systematic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library for relevant studies published up to August 2025. Two independent reviewers extracted data from the eligible studies, extracting baseline data, treatment protocols, follow-up duration, and clinical and radiological outcomes (EDSS and T1/T2 lesion counts). The statistical analyses were performed using R v4.3.3.
Results:
We collected 5,627 records from four databases after excluding 577 duplicates, with 67 articles included in the final analysis. Among the 35 studied DMTs, Alemtuzumab was superior in reducing relapse rates at 24 months (MD -1.02) and in maintaining a 12-month relapse-free state compared to placebo (RR 3.28) and other DMTs. Compared to placebo, the top-tier DMTs for relapse reduction were Alemtuzumab, Biosimilar Ocrelizumab (MD -0.84), Originator Ocrelizumab (MD -0.80), and Mitoxantrone (MD -0.73). For MRI outcomes, the combination of Ponesimod and DMF was most effective at reducing T1 lesions (MD -2.15), while Biosimilar Natalizumab (RR 2.86) and its originator (RR 2.66) were the best for preventing new T2 lesions. Disability progression varied by time. At 6 months, SC IFNbeta-1b (RR 0.14) and SC Ofatumumab (RR 0.33) were associated with the lowest disability progression. At 12 and 24 months, Mitoxantrone was associated with the lowest risk (RR 0.06 for both) of disability progression. Alemtuzumab was also the most effective at reducing EDSS at 6 and 12 months.
Conclusions:
Alemtuzumab and the Ocrelizumab formulations were highly effective for relapse prevention, while Ponesimod + DMF and Natalizumab formulations reduced MRI lesions. Mitoxantrone was associated with long-term prevention of disability progression.
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