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A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries.
BMC Neurol. 2019 Jan 07; 19(1):5.BN

Abstract

BACKGROUND

Delayed-release dimethyl fumarate (DMF) has demonstrated efficacy and a favorable benefit-risk profile in phase 2 and 3 studies that enrolled predominantly white patients with relapsing-remitting multiple sclerosis (RRMS). In this study (APEX, Part I), we evaluated the efficacy/safety outcomes of DMF in a predominantly East Asian population of patients with RRMS.

METHODS

In this 24-week, randomized, double-blind, placebo-controlled phase 3 study, 225 patients, 142 of which were East Asian (63.4%), were enrolled: Japan (n = 114), South Korea (n = 20), Taiwan (n = 8), the Czech Republic (n = 42), and Poland (n = 40). Key exclusion criteria included diagnosis of neuromyelitis optica spectrum disorder. Stratified by country, patients were randomized 1:1 to receive DMF 240 mg twice daily or placebo. Clinical assessments, including neurological examination and EDSS scoring, were conducted at baseline and at weeks 12 and 24.

RESULTS

A total of 213 patients (95.1%) completed the study. From weeks 12 - 24, the total number of new gadolinium-enhancing (Gd+) lesions was reduced by 84% (p < 0.0001) in DMF compared with placebo. For the secondary endpoint, from baseline to week 24, the total number of new Gd+ lesions was reduced by 75% and the mean number of new/newly enlarging T2 hyperintense lesions was reduced by 63% (both p < 0.0001). Flushing and flushing-related symptoms, and gastrointestinal events were adverse events related to DMF treatment. Efficacy and safety results in the Japanese subgroup and the East Asian subgroup (which included patients from Japan, Taiwan, and South Korea) were consistent with the overall study population.

CONCLUSION

The strong efficacy and favorable benefit-risk profile of DMF extends to Japanese, and more broadly, East Asian patients with RRMS.

TRIAL REGISTRATION

This trial is registered on ClinicalTrials.gov (identifier: NCT01838668), April 20, 2013 (retrospectively registered). The registration can be found at the following URL: https://clinicaltrials.gov/ct2/show/NCT01838668.

Authors+Show Affiliations

Kansai Multiple Sclerosis Centre, Kyoto Min-iren Central Hospital, Nishinokyo-Kasuga-cho 16-44-409, Nakakyo-ku, Kyoto, 604-8453, Japan. saida_takahiko@maia.eonet.ne.jp.NCNP, National Center Hospital, Tokyo, Japan.Kansai Medical University Medical Center, Osaka, Japan.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA. Sanofi, Cambridge, MA, USA.Biogen, Cambridge, MA, USA. Faculty of Pharmaceutical Medicine, London, UK.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

30616596

Citation

Saida, Takahiko, et al. "A Randomized Placebo-controlled Trial of Delayed-release Dimethyl Fumarate in Patients With Relapsing-remitting Multiple Sclerosis From East Asia and Other Countries." BMC Neurology, vol. 19, no. 1, 2019, p. 5.
Saida T, Yamamura T, Kondo T, et al. A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries. BMC Neurol. 2019;19(1):5.
Saida, T., Yamamura, T., Kondo, T., Yun, J., Yang, M., Li, J., Mahadavan, L., Zhu, B., & Sheikh, S. I. (2019). A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries. BMC Neurology, 19(1), 5. https://doi.org/10.1186/s12883-018-1220-3
Saida T, et al. A Randomized Placebo-controlled Trial of Delayed-release Dimethyl Fumarate in Patients With Relapsing-remitting Multiple Sclerosis From East Asia and Other Countries. BMC Neurol. 2019 Jan 7;19(1):5. PubMed PMID: 30616596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries. AU - Saida,Takahiko, AU - Yamamura,Takashi, AU - Kondo,Takayuki, AU - Yun,Jang, AU - Yang,Minhua, AU - Li,Jie, AU - Mahadavan,Lalitha, AU - Zhu,Bing, AU - Sheikh,Sarah I, Y1 - 2019/01/07/ PY - 2017/07/27/received PY - 2018/12/06/accepted PY - 2019/1/9/entrez PY - 2019/1/9/pubmed PY - 2019/2/12/medline KW - Delayed-release dimethyl fumarate KW - East Asia KW - Japan KW - Magnetic resonance imaging KW - Multiple sclerosis KW - Randomized clinical trial SP - 5 EP - 5 JF - BMC neurology JO - BMC Neurol VL - 19 IS - 1 N2 - BACKGROUND: Delayed-release dimethyl fumarate (DMF) has demonstrated efficacy and a favorable benefit-risk profile in phase 2 and 3 studies that enrolled predominantly white patients with relapsing-remitting multiple sclerosis (RRMS). In this study (APEX, Part I), we evaluated the efficacy/safety outcomes of DMF in a predominantly East Asian population of patients with RRMS. METHODS: In this 24-week, randomized, double-blind, placebo-controlled phase 3 study, 225 patients, 142 of which were East Asian (63.4%), were enrolled: Japan (n = 114), South Korea (n = 20), Taiwan (n = 8), the Czech Republic (n = 42), and Poland (n = 40). Key exclusion criteria included diagnosis of neuromyelitis optica spectrum disorder. Stratified by country, patients were randomized 1:1 to receive DMF 240 mg twice daily or placebo. Clinical assessments, including neurological examination and EDSS scoring, were conducted at baseline and at weeks 12 and 24. RESULTS: A total of 213 patients (95.1%) completed the study. From weeks 12 - 24, the total number of new gadolinium-enhancing (Gd+) lesions was reduced by 84% (p < 0.0001) in DMF compared with placebo. For the secondary endpoint, from baseline to week 24, the total number of new Gd+ lesions was reduced by 75% and the mean number of new/newly enlarging T2 hyperintense lesions was reduced by 63% (both p < 0.0001). Flushing and flushing-related symptoms, and gastrointestinal events were adverse events related to DMF treatment. Efficacy and safety results in the Japanese subgroup and the East Asian subgroup (which included patients from Japan, Taiwan, and South Korea) were consistent with the overall study population. CONCLUSION: The strong efficacy and favorable benefit-risk profile of DMF extends to Japanese, and more broadly, East Asian patients with RRMS. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov (identifier: NCT01838668), April 20, 2013 (retrospectively registered). The registration can be found at the following URL: https://clinicaltrials.gov/ct2/show/NCT01838668. SN - 1471-2377 UR - https://www.unboundmedicine.com/medline/citation/30616596/A_randomized_placebo_controlled_trial_of_delayed_release_dimethyl_fumarate_in_patients_with_relapsing_remitting_multiple_sclerosis_from_East_Asia_and_other_countries_ L2 - https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-018-1220-3 DB - PRIME DP - Unbound Medicine ER -