Diroximel fumarate 231mg gastro-resistant capsules

Abstract Objective To evaluate the safety and efficacy of Diroximel Fumarate (DRF) in patients with different relapsing forms of MS (RMS) through systematic review and meta-analysis. Methods A systematic review and meta-analysis adhering to PRISMA guidelines was conducted. Scopus, PubMed, and Cochrane CENTRAL databases were searched until December 6, 2024, for clinical trials and observational studies on DRF in RMS. Eligibility criteria included studies evaluating DRF’s safety or efficacy, excluding case reports and non-clinical outcomes. The risk of bias was assessed using the Newcastle–Ottawa Scale and ROBINS-I tools. Statistical analyses were performed using OpenMetaAnalyst, focusing on pooled mean differences and incidence rates with 95% confidence intervals. Results Seven studies with 3,075 participants were included. The overall persistence rate was 75.6% (95% CI: 63.5%, 87.7%). The discontinuation rate due to safety concerns was 6.1% (95% CI: 4.1%, 8.1%). Lymphocyte count decreased significantly by -355.02 cells/µL (95% CI: -636.71, -73.32). Mild adverse events (AEs) occurred in 33% (95% CI: 18.6%, 47.4%), moderate in 30% (95% CI: -9.9%, 69.9%), and severe in 5% (95% CI: -3.8%, 13.7%). Gastrointestinal (GI) AEs were observed in 17.4% (95% CI: 6%, 28.8%), flushing in 18.5% (95% CI: 5.7%, 31.3%), and lymphopenia in 24.3% (95% CI: 10.2%, 38.4%). The relapse rate was 7.1% (95% CI: -4.8%, 19%). Conclusion DRF demonstrates efficacy in reducing relapse rates and offers an improved safety profile compared to its predecessor, Dimethyl Fumarate (DMF), particularly in GI tolerability. However, lymphopenia requires monitoring. Further research is recommended to evaluate long-term safety and efficacy in diverse populations.

Abstract licence: CC BY 4.0

BackgroundRelapsing-Remitting Multiple Sclerosis (RRMS) is a chronic inflammatory demyelinating disease affecting the central nervous system, characterized by complex pathogenesis and increasing annual incidence rates. Although current clinical interventions for RRMS are diverse, there remains a relative scarcity of direct comparative studies on the efficacy and safety profiles among different oral disease-modifying drugs, resulting in insufficient comprehensive evidence.ObjectiveThis study aims to apply network meta-analysis techniques to systematically evaluate the relative efficacy and safety of different disease-modifying oral drugs in the treatment of RRMS, clarify their differences, and provide high-quality evidence-based medical support for optimal clinical treatment decision-making.MethodsThe systematic search was conducted in PubMed, Embase, Web of Science, and The Cochrane Register of Clinical Trials databases, covering the period from database inception to July 31, 2025. Randomized controlled trials were included, with study populations consisting of adult patients with relapsing-remitting multiple sclerosis, interventions involving disease-modifying oral medications, and comparators being placebo or other treatments. The primary data sources were phase II/III clinical trials, with non-standard treatment regimens serving as crucial observational approaches and thus analyzed as independent nodes for comparison. Primary outcome measures included Annualized relapse rate and Adverse events leading to discontinuation, while secondary outcomes comprised Adverse events, Serious adverse events, active T1 lesions, and active T2 lesions. A random-effects model was employed for network meta-analysis, with dichotomous and continuous variables analyzed using odds ratios (OR) and mean differences (MD) along with their respective 95% confidence intervals (CI) as effect measures to compare various interventions. Treatment rankings were performed using the surface under the cumulative ranking curve (SUCRA) probability method.ResultsA total of 15 RCTs involving 14,869 participants were included. The NMA results demonstrated that Siponimod, Ponesimod, Laquinimod, Fingolimod, Cladribine, and Dimethyl Fumarate were all superior to placebo in reducing annualized relapse rates in patients with multiple sclerosis, with Siponimod (2 mg; SUCRA = 86.9%) and Laquinimod 0.3 mg (SUCRA = 10.1%) being the best and worst treatments, respectively. Regarding adverse events leading to study discontinuation, the optimal and least favorable interventions were Fingolimod (0.25 mg; SUCRA = 83.1%) and Siponimod (10 mg; SUCRA = 3.1%), respectively.ConclusionsThis NMA demonstrated that Siponimod (2mg) is the most efficacious therapeutic intervention; FIN (0.25 mg) exhibited relative safety advantages in terms of DAE, though this dosage constitutes an exploratory regimen and should not serve as the basis for routine clinical medication. However, these findings still require further validation in subsequent studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420250654500.

Abstract licence: CC BY

IntroductionThis study assessed the cost-effectiveness of ozanimod compared with commonly used disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS).MethodsAnnualized relapse rate (ARR) and safety data were obtained from a network meta-analysis (NMA) of clinical trials of RRMS treatments including ozanimod, fingolimod, dimethyl fumarate, teriflunomide, interferon beta-1a, interferon beta-1b, and glatiramer acetate. ARR-related number needed to treat (NNT) relative to placebo and annual total MS-related healthcare costs was used to estimate the incremental annual cost per relapse avoided with ozanimod vs each DMT. ARR and adverse event (AE) data were combined with drug costs and healthcare costs to manage relapses and AEs in order to estimate annual cost savings with ozanimod vs other DMTs, assuming a 1 million USD fixed treatment budget.ResultsTreatment with ozanimod was associated with lower incremental annual healthcare costs to avoid a relapse, ranging from $843,684 vs interferon beta-1a (30 μg; 95% confidence interval [CI] - $1,431,619, - $255,749) to $72,847 (95% CI - $153,444, $7750) vs fingolimod. Compared with all other DMTs, ozanimod was associated with overall healthcare cost savings ranging from $8257 vs interferon beta-1a (30 μg) to $2178 vs fingolimod. Compared with oral DMTs, ozanimod was associated with annual cost savings of $6199 with teriflunomide 7 mg, $4737 with teriflunomide 14 mg, $2178 with fingolimod, and $2793 with dimethyl fumarate.ConclusionTreatment with ozanimod was associated with substantial reductions in annual drug costs and total MS-related healthcare costs to avoid relapses compared with other DMTs. In the fixed-budget analysis, ozanimod demonstrated a favorable cost-effective profile relative to other DMTs.

Abstract licence: CC BY-NC