Tecfidera (dimethyl fumarate) is a disease-modifying agent by Biogen for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS).1 The treatment may also be used in adult patients with clinically isolated syndrome (CIS) and active secondary progressive multiple sclerosis (SPMS).2
The US Food and Drug Administration (FDA) has approved Tecfidera and generic forms of the treatment. It is also authorized for use in the European Union.3
Tecfidera is an oral capsule containing 120 or 240 mg of dimethyl fumarate. The recommended dose is 120 mg twice daily for a week and then 240 mg twice daily.4
The safety and efficacy of Tecfidera for the treatment of pediatric patients have not been established.1
Mechanism of Action
Although the exact mechanism of action of Tecfidera is not fully understood, it is thought to modulate the immune response and reduce inflammation.2 Tecfidera may also have antioxidant properties acting through the Nrf2 protein, which regulates certain genes that produce antioxidants.3 This could protect neurons in the brain and spinal cord from the damage caused by multiple sclerosis (MS).
Warnings, Precautions, and Adverse Reactions
Tecfidera may cause serious side effects such as allergic reactions including welts, hives, and swelling, serious infections including progressive multifocal leukoencephalopathy (which may be lethal), herpes zoster infections, decreased white blood cell count, and hepatic problems.1
Get detailed prescribing information on the Tecfidera monograph page on Rare Disease Advisor.
The most common side effects of Tecfidera are flushing, redness, itching, rash, nausea, vomiting, diarrhea, stomach pain, and indigestion.
It is not known whether Tecfidera is harmful to the fetus or if it passes into breast milk.
Efficacy in Clinical Trials
The safety and efficacy of Tecfidera in treating RRMS have been tested in a phase 3 clinical trial called DEFINE.5 The randomized, multicenter, double-blind, placebo-controlled, dose-comparison study recruited 1234 patients aged 18 to 55 years with RRMS and an Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0.
Participants were randomly assigned to receive either 240 mg of oral Tecfidera either 2 or 3 times a day or a placebo.
The primary endpoint of the study was the proportion of participants who relapsed. Secondary endpoints were the number of new or newly enlarging T2 hyperintense lesions on magnetic resonance imaging (MRI), the number of gadolinium-enhancing T1-weighted lesions on MRI, the number of participants with gadolinium-enhancing lesions, the annualized relapse rates, and the proportion of participants experiencing disability progression.
The results showed that the annualized relapse rate was significantly lower in patients being treated with either dose of Tecfidera compared to those who were treated with the placebo.6 The estimated proportion of patients with confirmed progression of disability was also lower in the Tecfidera group compared to the placebo group. Finally, Tecfidera treatment significantly reduced the number of gadolinium-enhancing lesions and new or enlarging T2-weighted hyperintense lesions compared to the placebo.
Another phase 3 clinical trial called CONFIRM also tested the safety and efficacy of Tecfidera and compared the risks and benefits of Tecfidera treatment to glatiramer acetate.7 The study recruited 1417 participants aged 18 to 55 years with RRMS and an EDSS score between 0.0 and 5.0.
The primary endpoint of the study was the annualized relapse rate. Secondary endpoints were the number of new or newly enlarging T2 hyperintense lesions on MRI, the number of new T1 hypointense lesions on MRI, the proportion of patients who relapsed, and the proportion of patients who experienced disability progression.
The results showed that the annualized relapse rate was significantly lower in patients treated with Tecfidera or glatiramer acetate compared to those given the placebo.8 However, there were no statistically significant differences in terms of reductions in disability progression between patients treated with Tecfidera, glatiramer acetate, or the placebo. However, treatment with both Tecfidera and glatiramer acetate significantly reduced the numbers of new or enlarging T2-weighted hyperintense lesions and new T1-weighted hypointense lesions compared to the placebo.
An integrated analysis of the data from both the DEFINE and CONFIRM trials was conducted to evaluate the effect of Tecfidera in patients who were previously treated with interferon beta. The results showed that Tecfidera demonstrated significant efficacy over 2 years compared to the placebo in patients previously treated with interferon beta.9
A phase 3 extension study called ENDORSE evaluated the long-term safety and efficacy of Tecfidera in 1736 participants who previously completed the DEFINE or CONFIRM trials.10
Of the 1736 patients who enrolled, 760 completed the study. Patients were followed for a median of 6.76 years in ENDORSE and a median of 2 years in DEFINE and CONFIRM. Overall, 60% of patients treated with Tecfidera throughout the studies and 66% of those first treated with the placebo and then Tecfidera remained relapse-free. Patients retained the ability to walk throughout.
Similarly, 72% of patients treated with Tecfidera throughout and 73% of patients first treated with the placebo then Tecidera remained relapse-free. Tecfidera had no 24-week confirmed disability progression over 10 years, supporting Tecfidera as a long-term option for patients with relapsing forms of MS.11
- Tecfidera® (dimethyl fumarate). Biogen. Accessed June 15, 2021.
- Tecfidera. National Multiple Sclerosis Society. Accessed June 15, 2021.
- Tecfidera: dimethyl fumarate. European Medicines Agency. Updated April 20, 2021. Accessed June 15, 2021.
- Tecfidera dosage. Drugs.com. Updated January 31, 2021. Accessed June 15, 2021.
- Efficacy and safety of oral BG00012 in relapsing-remitting multiple sclerosis (DEFINE). ClinicalTrials.gov. January 11, 2007. Updated January 26, 2015. Accessed June 15, 2021.
- Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098-1107. doi:10.1056/NEJMoa1114287
- Efficacy and safety study of oral BG00012 with active reference in relapsing-remitting multiple sclerosis (CONFIRM). ClinicalTrials.gov. March 23, 2007. Updated January 26, 2015. Accessed June 15, 2021.
- Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087-1097. doi:10.1056/NEJMoa1206328
- Fernández Ó, Giovannoni G, Fox RJ, et al. Efficacy and safety of delayed-release dimethyl fumarate for relapsing-remitting multiple sclerosis in prior interferon users: an integrated analysis of DEFINE and CONFIRM. Clin Ther. 2017;39(8):1671-1679. doi:10.1016/j.clinthera.2017.06.012
- BG00012 monotherapy safety and efficacy extension study in multiple sclerosis (MS) (ENDORSE). ClinicalTrials.gov. February 4, 2009. Updated December 31, 2020. Accessed June 15, 2021.
- Gold R, Arnold DL, Bar-Or A, et al. Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE. Ther Adv Neurol Disord. 2020;13:1756286420915005. doi:10.1177/1756286420915005
Reviewed by Kyle Habet, MD, on 7/1/2021.