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Background: Interferon beta-1a remains an important treatment option for multiple sclerosis, particularly when safety or tolerability concerns may outweigh the benefits of higher-efficacy disease-modifying therapies. The five-year phase 4 Plegridy Observational Program (POP) study (NCT02230969) collected data on real-world safety and effectiveness of Plegridy® (peginterferon beta-1a) treatment in patients with relapsing multiple sclerosis., Objective: To explore the real-world safety and effectiveness of peginterferon beta-1a in patients with relapsing multiple sclerosis, including factors influencing treatment discontinuation., Methods: Data were collected prospectively from patients ≥ 18 years old with relapsing multiple sclerosis for overall population analysis and for subpopulations including newly/previously diagnosed patients, age, and experience with peginterferon beta-1a. Outcome measures included annualized relapse rates, adverse events, and predictors of time to treatment discontinuation., Results: Mean (SD) treatment duration in the overall population ( N  = 1172) was 896.0 (733.15) days. Incidence of adverse events was higher in new than experienced users (79.4% vs. 57.0%). New users were more likely than experienced users to discontinue (hazard ratio = 1.60; P  < 0.0001). The adjusted annualized relapse rate was 0.09, and at the end of 5 years, 77.1% of patients were relapse-free., Conclusions: Peginterferon beta-1a is an effective therapy for managing relapsing multiple sclerosis. The identification of predictors of discontinuation can help inform strategies to enhance treatment persistence., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MS has received grant support and/or speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi, and Teva Neuroscience. SW is a paid consultant, speaker, and/or contract researcher for Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, Receptos, and TG Therapeutics. GN has received speaker honoraria from Bayer, Biogen, Celgene, Merck, Novartis, and Roche. NB, AK, WC-B, and MV are employees of and may hold stock and/or stock options in Biogen. TK was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen., (© The Author(s), 2024.)

Background: Multiple sclerosis (MS) comparative effectiveness research needs to go beyond average treatment effects (ATEs) and post-host subgroup analyses., Objective: This retrospective study assessed overall and patient-specific effects of dimethyl fumarate (DMF) versus teriflunomide (TERI) in patients with relapsing-remitting MS., Methods: A novel precision medicine (PM) scoring approach leverages advanced machine learning methods and adjusts for imbalances in baseline characteristics between patients receiving different treatments. Using the German NeuroTransData registry, we implemented and internally validated different scoring systems to distinguish patient-specific effects of DMF relative to TERI based on annualized relapse rates, time to first relapse, and time to confirmed disease progression., Results: Among 2791 patients, there was superior ATE of DMF versus TERI for the two relapse-related endpoints ( p  = 0.037 and 0.018). Low to moderate signals of treatment effect heterogeneity were detected according to individualized scores. A MS patient subgroup was identified for whom DMF was more effective than TERI ( p  = 0.013): older (45 versus 38 years), longer MS duration (110 versus 50 months), not newly diagnosed (74% versus 40%), and no prior glatiramer acetate usage (35% versus 5%)., Conclusion: The implemented approach can disentangle prognostic differences from treatment effect heterogeneity and provide unbiased patient-specific profiling of comparative effectiveness based on real-world data., Competing Interests: X Jiang, G Simoneau, A Harrington, W Castro-Borrero, C de Moor, F Pellegrini are employees and former employees of and hold stock/stock options in Biogen. L Tian received consulting fees from Biogen. M Zuercher, P van Hoevell, and Y Heer are employees of Rewoso AG, Zürich, Switzerland. A Bergmann has received consulting fees from advisory board, speaker, and other activities for NeuroTransData; project management and clinical studies for and travel expenses from Novartis and Servier. S Braune has received honoraria from Kassenaerztliche Vereinigung Bayern and health maintenance organizations for patient care; honoraria for consulting, project management, clinical studies, and lectures and from Biogen, Eli Lilly, Merck, NeuroTransData, Novartis, Roche, and Thieme Verlag; honoraria and expense compensation as board member of NeuroTransData., (© The Author(s), 2023.)

Background: EXTEND (NCT01797965), an open-label extension study, evaluated the safety and efficacy of daclizumab beta in participants with relapsing multiple sclerosis (MS) who had completed the randomized DECIDE study., Methods: Eligible participants who received either daclizumab beta or interferon beta-1a in DECIDE received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 5 years in EXTEND, followed by 24 weeks of post-dosing follow-up. Safety and tolerability were evaluated, as were clinical efficacy and magnetic resonance imaging (MRI). EXTEND was terminated ahead of schedule by the sponsors., Results: The total safety population ( N  = 1203) received at least one dose of daclizumab beta in EXTEND. In the DECIDE and EXTEND combined periods, the median number of doses of daclizumab beta was 53; median time on treatment was 196 weeks. By 24 September 2018, the end of the study, 110/1203 (9%) participants had completed the protocol-specified treatment period and 1101/1203 (92%) had experienced an adverse event (AE). The most commonly reported AEs were MS relapse, nasopharyngitis, and upper respiratory tract infection. Hepatic events (18%), cutaneous events (45%), and infections (62%) were common treatment-related AEs. The incidence of serious AEs was 29%, most commonly MS relapse and infections. The incidence of immune-mediated disorders was 2%; three of seven were encephalitis. Two of six deaths were considered treatment related. In participants who received continuous daclizumab beta throughout DECIDE and EXTEND, the treatment effects on clinical and MRI outcomes were maintained for up to 6 years., Conclusion: Results from the combined DECIDE-EXTEND study elucidate outcomes of longer-term treatment with daclizumab beta in the clinical trial setting and underscore the importance of pharmacovigilance with immunomodulatory therapies in the real-world setting., Competing Interests: Conflict of interest: LK reports funding to his institution (University Hospital Basel) in the last 3 years used exclusively for research support; steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer, Biogen, Celgene, Genzyme, Merck, Mitsubishi, Novartis, Pfizer, Sanofi, and Santhera; speaker fees from Biogen, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer, Biogen, European Union, Innosuisse, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and Swiss National Research Foundation. SC reports speaking honoraria from and/or advisory boards for Biogen, Bristol Myers Squibb, EMD Serono, Novartis, Pear Therapeutics, Roche Genentech, and Sanofi Genzyme; and research support from AbbVie, Acorda, Actelion, Biogen, MedDay, Novartis, Roche Genentech, and Sanofi Genzyme. DLA reports consultant fees and/or grants from Acorda, Adelphi, Alkermes, Biogen, Canadian Institutes of Health Research, Celgene, Frequency Therapeutics, Genentech, Genzyme, Immune Tolerance Network, Immunotec, International Progressive MS Alliance, MedDay, Merck Serono, MS Society of Canada, Novartis, Pfizer, Receptos, Roche, and Sanofi and an equity interest in NeuroRx Research. RRR is an employee of and holds stock/stock options in AbbVie. JH was a former employee of and holds stock/stock options in AbbVie. BP was a former employee of and holds stock/stock options in Biogen. SF, SX and WC-B are employees of and hold stock/stock options in Biogen. The EXTEND study and these analyses were funded by Biogen (Cambridge, MA, USA) and AbbVie (Redwood City, CA, USA)., (© The Author(s), 2021.)

Multiple sclerosis (MS) is a potentially disabling chronic autoimmune neurological disease that mainly affects young adults. Our understanding of the pathophysiology of MS has significantly advanced in the past quarter of a century. This has led to the development of many disease-modifying therapies (DMTs) that prevent exacerbations and new lesions in patients with relapsing remitting MS (RRMS). So far there is no drug available that can completely halt the neurodegenerative changes associated with the disease. It is the purpose of this review to provide concise information regarding mechanism of action, indications, side effects and safety of Food and Drug Administration and European Medicines Agency approved agents for MS, emerging therapies, and drugs that can be considered for off-label use in MS.