Evidence map›Paper›PMID 30206820›Full record

Trial reportAdvances in therapy2018

72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label Extension.

Hirofumi Ochi, Masaaki Niino, Yasuhiro Onizuka, Katsutoshi Hiramatsu, Masakazu Hase, Jang Yun, André Matta, Shinichi Torii

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Advances in therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01838668 (A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of BG00012 in Subjects From the Asia-Pacific Region and Other Countries With Relapsing-Remitting Multiple Sclerosis), which is not on this map. Cited by 13 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01838668 phase3completednot on this map

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of BG00012 in Subjects From the Asia-Pacific Region and Other Countries With Relapsing-Remitting Multiple Sclerosis

TypeinterventionalSponsorBiogenRan2013 to 2018Enrolled225ConditionsRelapsing-Remitting Multiple Sclerosis, Multiple SclerosisArmsPlacebo, dimethyl fumarate
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Observational
  5. Article
  6. Review
  7. Review
  8. Current Landscape of NRF2 Biomarkers in Clinical Trials.Antioxidants (Basel, Switzerland) · 2020
    Review
  9. Review
  10. Article
  11. Article
  12. T lymphopenia in multiple sclerosis patients treated with ofatumumab: Even with consideration for CD3Multiple sclerosis journal - experimental, translational and clinical
    Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Hirofumi OchiDepartment of Geriatric Medicine and Neurology, Ehime University Graduate School of Medicine, Ehime, Japan. hochi@m.ehime-u.ac.jp.
Masaaki NiinoDepartment of Clinical Research, Hokkaido Medical Center, Sapporo, Japan.
Yasuhiro OnizukaBiogen Japan Ltd., Tokyo, Japan.
Katsutoshi HiramatsuBiogen Japan Ltd., Tokyo, Japan.
Masakazu HaseBiogen Japan Ltd., Tokyo, Japan.
Jang YunBiogen Inc., Cambridge, USA.
André MattaBiogen Inc., Cambridge, USA.
Shinichi ToriiBiogen Japan Ltd., Tokyo, Japan.
Japan Bio Products (Japan) · JPBiogen (United States) · USEhime University · JPNational Hospital Organization Hokkaido Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe long-term safety of dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly Caucasian patients. The present interim analysis aimed to evaluate the 72-week safety of DMF in Japanese patients with RRMS.

methodsSafety data of Japanese subjects enrolled in the 24-week randomised, double-blind, placebo-controlled APEX study (Part I) and its following open-label extension (Part II) were analysed at 72 weeks from the beginning of Part I. In Part I, subjects were randomised to DMF treatment or matching placebo while all subjects received DMF treatment during Part II. Adverse events (AEs) reported throughout the study period were recorded.

resultsOverall, 109 Japanese subjects completed 72 weeks of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively, in the DMF group compared with 84% and 18%, respectively, in the placebo group at 24 weeks. Common AEs (at least 5%) reported with treatment included nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash, headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AEs led to discontinuation of DMF in 5% of patients and included MS relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an initial decrease from baseline of 17% in the DMF group at week 24, the mean lymphocyte counts stabilised and were maintained until week 72. No opportunistic/serious infections nor malignancies were reported with DMF treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs were similar between the DMF and the placebo groups.

conclusionThe 72-week safety profile of DMF in Japanese patients with RRMS was consistent with previous studies that enrolled mostly Caucasian patients, with a lower incidence of flushing and related symptoms and a lower reduction in the lymphocyte count compared with previous reports.

trial registrationClinicalTrials.gov identifier NCT01838668.

fundingBiogen Japan Ltd.

Indexed as

Dimethyl FumarateDrug-Related Side Effects and Adverse ReactionsAdultDouble-Blind MethodFemaleHumansImmunosuppressive AgentsIncidenceJapanMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingRecurrenceTreatment OutcomeDimethyl FumarateImmunosuppressive AgentsAPEXDimethyl fumarateJapanesePhase 3Relapsing-remitting multiple sclerosisSafety

Identifiers

PMID30206820
PMCPMC6182629
OpenAlexW2889881055

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.