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The International Journal of... 2015Trials of dimethyl fumarate (DMF) and teriflunomide, two new oral therapies for relapsing-remitting multiple sclerosis (RRMS) were recently published [1, 2, 3]. A... (Meta-Analysis)
Meta-Analysis
Meta-analysis of adverse events in recent randomized clinical trials for dimethyl fumarate, glatiramer acetate and teriflunomide for the treatment of relapsing forms of multiple sclerosis.
PURPOSE/AIM OF THE STUDY
Trials of dimethyl fumarate (DMF) and teriflunomide, two new oral therapies for relapsing-remitting multiple sclerosis (RRMS) were recently published [1, 2, 3]. A comparison of their safety against glatiramer acetate-a prevalent injectable treatment-is relevant to inform therapy-switching decisions. The study objective was to conduct a systematic review and mixed treatment comparison of total AEs in RCTs of dimethyl fumarate 240 mg bid (DMF2) or tid (DMF3), glatiramer acetate 20 mg injectable daily (GA), and teriflunomide 7 mg (TERI7) or 14 mg (TERI14) daily in RRMS patients.
MATERIALS AND METHODS
Articles were selected following Cochrane guidelines. A network meta-analysis was used to compare the odds of patients experiencing at least one AE between drugs, using placebo as baseline. Drugs were compared using the odds ratio (OR), credible interval (CrI), and confidence in OR≥1 (PrOR). The mean rank (best=1) and corresponding Surface-Under-Cumulative-Ranking (SUCRA) (best=100%) were reported.
RESULTS
3737 patients from three RCTs were included for analysis. Patients receiving GA exhibited the lowest AEs (DMF2 [OR=2.67, PrOR=98.7%], DMF3 [OR=1.92, PrOR=95.3%], Teri7 [OR=2.74, PrOR=95.2%], Teri14 [OR=3.03, PrOR=96.4%]), and equivalent to PB (OR=1.60; PrOR=94.3%). No other significant differences were found. GA also ranked with the lowest AEs (rank=1.2, SUCRA=96.0%), whereas DMF2 and Teri14 ranked highest (rank=4.8).
CONCLUSIONS
RRMS patients treated with glatiramer have the lowest odds of experiencing AEs, while patients taking DMF or teriflunomide have similar, higher odds of developing AEs, suggesting that patients treated with glatiramer may have higher QoL than patients under DMF or teriflunomide.
Topics: Crotonates; Dimethyl Fumarate; Gastrointestinal Diseases; Glatiramer Acetate; Humans; Hydroxybutyrates; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Nitriles; Randomized Controlled Trials as Topic; Toluidines; Treatment Outcome
PubMed: 25387069
DOI: 10.3109/00207454.2014.979982 -
Multiple Sclerosis and Related Disorders Dec 2022There is a lack of safety information about the post-marketing adverse effects of several disease-modifying drugs (DMDs) used to control multiple sclerosis (MS).... (Review)
Review
BACKGROUND
There is a lack of safety information about the post-marketing adverse effects of several disease-modifying drugs (DMDs) used to control multiple sclerosis (MS). Investigating the post-marketing side effects is required to manifest the safety of the appropriate therapy. Therefore, the present systematic review aimed to identify disease-modifying drugs used to control multiple sclerosis attacks and progress.
METHODS
The Web of Science, PubMed, and Scopus databases were searched for studies published until November 2020 based on the research strategy terms. Inclusion criteria involved all full texts exploring disease-modifying drugs used to control multiple sclerosis based on case reports and case series studies. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the quality of case report studies.
RESULTS
In total, 25 articles that met the criteria for inclusion were retrieved in the present systematic review. The most side effects were observed with fingolimod and teriflunomide, respectively, while dimethyl fumarate had minor side effects.
CONCLUSION
The oral therapies have some significant post-marketing adverse effects that have been diagnosed in numerous case reports. Some of them are serious and must be noticed by neurologists. Accordingly, in this review, we assessed the post-marketing adverse effects of oral therapies for multiple sclerosis.
Topics: Humans; Multiple Sclerosis; Immunosuppressive Agents; Dimethyl Fumarate; Fingolimod Hydrochloride; Drug-Related Side Effects and Adverse Reactions; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36122472
DOI: 10.1016/j.msard.2022.104157 -
Current Journal of Neurology Jul 2020Although widely used, first-line injectable medicines for the treatment of multiple sclerosis (MS) remain an issue of efficacy and adherence. Recently, new oral...
Although widely used, first-line injectable medicines for the treatment of multiple sclerosis (MS) remain an issue of efficacy and adherence. Recently, new oral medications for MS have contributed to dramatic improvements in MS treatment. This study aims to evaluate the safety and efficacy of oral disease-modifying drugs (DMDs) used in relapsing-remitting MS (RRMS). A systematic review was conducted on related databases including PubMed, Scopus, Cochrane, and Web of Science up to April 2020. The screening of the studies and their quality assessment was carried out independently by the two authors. Three studies fulfilled the predefined criteria of inclusion. One of them compared teriflonomide with subcutaneous interferon beta-1a (IFN β-1a), another compared oral fingolimod with intramuscular (IM) IFN β-1b, and the third article compared oral fingolimod with IM IFN β-1a. No eligible study was found for dimethyl fumarate (DMF). The results indicated that while the efficacy of fingolimod was more than IFN β (IM β-1a and β-1b), teriflunomide 7 mg had less efficacy than subcutaneous IFN β-1a. Regarding safety, the results indicated that the proportion of diabetic patients with adverse events (AEs) in the fingolimod group was higher than in the IFN β-1b group and the overall occurrence of AEs was similar between teriflunomide and IFN β-1a groups. There is evidence for the effectiveness of fingolimod in reducing annualized relapse rates (ARRs) and improving magnetic resonance imaging (MRI) findings, but the evidence does not support the effectiveness of teriflunomide and further studies are required to determine its efficacy. Also, fingolimod is associated with more side effects than IFN β-1b, but there is no evidence to suggest any difference in side effects between teriflunomide and IFN β-1a.
PubMed: 38011404
DOI: 10.18502/cjn.v19i3.5427 -
Current Medical Research and Opinion Feb 2019The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic...
BACKGROUND
The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence.
REVIEW
This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs.
CONCLUSIONS
Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.
Topics: Africa, Northern; Humans; Immunosuppressive Agents; Middle East; Multiple Sclerosis, Relapsing-Remitting
PubMed: 29764226
DOI: 10.1080/03007995.2018.1476334 -
Multiple Sclerosis and Related Disorders Feb 2019
Topics: Crotonates; Dimethyl Fumarate; Fingolimod Hydrochloride; Humans; Hydroxybutyrates; Immunosuppressive Agents; Medication Adherence; Multiple Sclerosis; Nitriles; Toluidines
PubMed: 30590239
DOI: 10.1016/j.msard.2018.12.025