October 3, 2012Volume 7 - Issue 40     

DynaMed Weekly Update

For the week ending September 28, 2012

Last week 332 articles were evaluated via DynaMed's Systematic Literature Surveillance and 158 were added to DynaMed content.   


Based on the editors' criteria of selecting "articles most likely to change clinical practice," one article of significant interest was selected for the DynaMed Weekly Update.

Feature Article

Dimethyl Fumarate May Decrease Risk of Relapse in Relapsing-Remitting Multiple Sclerosis


Parenteral agents including interferon and glatiramer are the most common treatments for relapsing-remitting multiple sclerosis (MS), but adherence can be a concern. Oral alternatives to daily subcutaneous injection have been studied including the FDA-approved drugs fingolimod (Gilenya) and teriflunomide (Aubagio). Other oral agents that have shown benefit for reducing relapse rates but are not yet FDA-approved for this use include cladribine (Leustatin) (N Engl J Med 2010 Feb 4;362(5):416) and laquinimod (N Engl J Med 2012 Mar 15;366(11):1000). Another oral drug, dimethyl fumarate (BG-12), an antiinflammatory and cytoprotective agent, was submitted for FDA approval for use in relapsing-remitting MS in February 2012. Two recent randomized trials evaluated its efficacy.


In the CONFIRM trial, 1,430 adults with relapsing-remitting MS were randomized to dimethyl fumarate 240 mg orally (2 times daily vs. 3 times daily) vs. glatiramer 20 mg subcutaneously daily vs. oral placebo for 96 weeks.  Relapse was defined as new or recurrent neurologic symptoms (not associated with fever or infection) lasting for ≥ 24 hours and new objective neurologic findings. About 20% of patients withdrew during follow-up and 1% discontinued the study drug but completed the trial. The intention-to-treat analysis included 99% of randomized patients who received at least 1 dose of the study drug.


Both doses of dimethyl fumarate were associated with significantly reduced annualized relapse rates compared to placebo. The estimated 2-year risk of relapse was 29% for 2 times daily dosing (p < 0.05 vs. placebo, NNT 9), 24% for 3 times daily dosing (p < 0.05 vs. placebo, NNT 6), and 41% for placebo (level 2 [mid-level] evidence). Glatiramer was also associated with a significantly reduced risk of relapse (p < 0.05 vs. placebo). There were no significant differences in progression of disability at 2 years.The most common adverse events with dimethyl fumarate were flushing and gastrointestinal symptoms (N Engl J Med 2012 Sep 20;367(12):1087).


In the DEFINE trial, 1,237 adults were randomized to the same doses of oral dimethyl fumarate as above vs. placebo for 96 weeks. About 23% withdrew from the trial but were included in the intention-to-treat analysis. As in the CONFIRM trial, both doses of dimethyl fumarate were associated with significant reduction in annualized relapse rates compared to placebo. The estimated 2-year risk of relapse was 27% for 2 times daily dosing (p < 0.05 vs. placebo, NNT 6), 26% for 3 times daily dosing (p < 0.05 vs. placebo, NNT 5), and 46% for placebo (level 2 [mid-level] evidence). Unlike the CONFIRM trial, dimethyl fumarate was also associated with reduced risk of disability progression at 2 years, with estimated rates of 16% for 2 times daily dosing (p < 0.05, NNT 9), 18% for 3 times daily dosing (p < 0.05, NNT 12), and 27% for placebo (N Engl J Med 2012 Sep 20;367(12):1098). 



For more information, see the Multiple sclerosis topic in DynaMed.

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DynaMed Events 

First International Conference on Evidence Based HealthCare (ISEHCON), October 7th - 8th, 2012   

Editor-in-Chief Dr. Brian Alper will be leading a workshop at the First International Conference on Evidence Based Healthcare at the India International Centre in New Delhi, India. The topic of the workshop will be "Best Sources for Evidence-Based Literature for Healthcare Practitioners".   


Visit the International Society for Evidence Based Health Care website to learn more about the event and for registration information.

Call for Peer Reviewers

We are currently seeking reviewers for:  

Eastern equine encephalitis

Brachial plexopathy

Learn more about the DynaMed Contribution Opportunities:

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About DynaMed Weekly Update

Prepared by the clinician members of the DynaMed Editorial Team, DynaMed Weekly Update is a compilation of one to five articles selected from DynaMed's Systematic Literature Surveillance as articles most likely to change clinical practice.

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CME Information


0.25 AMA PRA Category I Credit(s)™
Family Physicians: 0.25 Prescribed credits
Nurse Practitioners: 0.25 Contact hours
Release Date: October 03, 2012
Expiration Date: October 03, 2013
Estimated Completion Time:
15 minutes
There is no fee for this activity.

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In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article.

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Learning Objectives
Upon successful completion of this educational program, the reader should be able to:
1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.
Faculty Information
Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA

Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company

Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.


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