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Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis.
Eur J Neurol. 2015 Apr; 22(4):664-71.EJ

Abstract

BACKGROUND AND PURPOSE

Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), demonstrated efficacy and safety in relapsing-remitting multiple sclerosis in the 2-year, randomized, placebo-controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF.

METHODS

Eligible patients were randomized to receive placebo, DMF 240 mg twice (BID) or three times (TID) daily or glatiramer acetate (GA; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis.

RESULTS

A total of 2301 patients were randomized and received treatment with placebo (n = 771) or DMF BID (n = 769) or TID (n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0-12 (BID, P = 0.0159; TID, P = 0.0314); the proportion of patients relapsed beginning at week 10 (BID, P = 0.0427) and week 12 (TID, P = 0.0451); and the proportion of patients with 12-week confirmed disability progression beginning at week 62 (BID, P = 0.0454) and week 72 (TID, P = 0.0399), compared with placebo. These effects were sustained throughout the 2-year study period. DMF significantly reduced the odds of having a higher number of gadolinium-enhancing lesions by 88% (BID) and 75% (TID) and the mean number of new or enlarging T2 lesions by 72% (BID) and 67% (TID), from the first post-baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo).

CONCLUSIONS

In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing-remitting multiple sclerosis.

Authors+Show Affiliations

Neurology, University Hospital, Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25557371

Citation

Kappos, L, et al. "Time Course of Clinical and Neuroradiological Effects of Delayed-release Dimethyl Fumarate in Multiple Sclerosis." European Journal of Neurology, vol. 22, no. 4, 2015, pp. 664-71.
Kappos L, Giovannoni G, Gold R, et al. Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. Eur J Neurol. 2015;22(4):664-71.
Kappos, L., Giovannoni, G., Gold, R., Phillips, J. T., Arnold, D. L., Hotermans, C., Zhang, A., Viglietta, V., & Fox, R. J. (2015). Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. European Journal of Neurology, 22(4), 664-71. https://doi.org/10.1111/ene.12624
Kappos L, et al. Time Course of Clinical and Neuroradiological Effects of Delayed-release Dimethyl Fumarate in Multiple Sclerosis. Eur J Neurol. 2015;22(4):664-71. PubMed PMID: 25557371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. AU - Kappos,L, AU - Giovannoni,G, AU - Gold,R, AU - Phillips,J T, AU - Arnold,D L, AU - Hotermans,C, AU - Zhang,A, AU - Viglietta,V, AU - Fox,R J, AU - ,, Y1 - 2015/01/02/ PY - 2014/08/04/received PY - 2014/10/17/accepted PY - 2015/1/6/entrez PY - 2015/1/6/pubmed PY - 2015/9/29/medline KW - MRI KW - delayed-release dimethyl fumarate KW - disability KW - multiple sclerosis KW - relapse KW - time course SP - 664 EP - 71 JF - European journal of neurology JO - Eur J Neurol VL - 22 IS - 4 N2 - BACKGROUND AND PURPOSE: Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), demonstrated efficacy and safety in relapsing-remitting multiple sclerosis in the 2-year, randomized, placebo-controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF. METHODS: Eligible patients were randomized to receive placebo, DMF 240 mg twice (BID) or three times (TID) daily or glatiramer acetate (GA; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis. RESULTS: A total of 2301 patients were randomized and received treatment with placebo (n = 771) or DMF BID (n = 769) or TID (n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0-12 (BID, P = 0.0159; TID, P = 0.0314); the proportion of patients relapsed beginning at week 10 (BID, P = 0.0427) and week 12 (TID, P = 0.0451); and the proportion of patients with 12-week confirmed disability progression beginning at week 62 (BID, P = 0.0454) and week 72 (TID, P = 0.0399), compared with placebo. These effects were sustained throughout the 2-year study period. DMF significantly reduced the odds of having a higher number of gadolinium-enhancing lesions by 88% (BID) and 75% (TID) and the mean number of new or enlarging T2 lesions by 72% (BID) and 67% (TID), from the first post-baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo). CONCLUSIONS: In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing-remitting multiple sclerosis. SN - 1468-1331 UR - https://www.unboundmedicine.com/medline/citation/25557371/Time_course_of_clinical_and_neuroradiological_effects_of_delayed_release_dimethyl_fumarate_in_multiple_sclerosis_ L2 - https://doi.org/10.1111/ene.12624 DB - PRIME DP - Unbound Medicine ER -