Tecfidera® (dimethyl fumarate)
FDA-Approved Medications: New Data on Previously Approved Medications: Oral Medications
- Starting dose: 120 mg twice a day, orally for seven days; ongoing dose: 240 mg twice a day, orally
- Approved in 2013 for RMS
The exact means by which Tecfidera® (dimethyl fumarate) exerts its effects in MS is not known. The medication has been shown to activate a pathway involved in the cellular response to oxidative stress, which is induced by inflammation. However, it is unclear whether this pathway activation plays a role in Tecfidera’s impact on the MS disease process.4
In 2017, the prescribing information for Tecfidera was revised to include direction to obtain a complete blood cell count and to measure liver enzymes and other values before initiating the medication. Additionally, warnings were added to the prescribing information noting that progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection, and liver injury, have occurred in people taking Tecfidera.4
A recent study found that patients with relapsing-remitting MS (RRMS) respond well to Tecfidera and generally adhere to treatment, regardless of whether they switched from a previous disease-modifying therapy or were being treated for the first time. The findings offer a glimpse into the real-world efficacy of Tecfidera, and may guide physicians’ use of the oral agent at various stages of RRMS.
Researchers reviewed the records of 456 people with RRMS at six MS treatment centers in Italy. These individuals either had started treatment with Tecfidera or switched to the medication from another DMT. Two of every three patients studied were women, and the group had a mean Expanded Disability Status Scale (EDSS) score of 2.5, indicating mild to moderate disability for many of these individuals. The participants’ mean age was 40 years, and mean MS disease duration was nine years.
The annualized relapse rate was reduced by 75% from baseline among those treated with Tecfidera. However, study participants with an elevated pre-treatment EDSS score (suggesting more-severe disability) were more likely to discontinue the medication, compared to those who had mild to moderate disability before treatment. Also, patients who de-escalated from a stronger but potentially more-toxic second-line therapy to Tecfidera faced an increased risk of relapse.
Among the other findings:
• EDSS scores were stable in 88% of patients.
• The younger the patient, the lower the risk of relapse.
• The shorter patients’ disease duration, the greater their chance of achieving no evidence of disease activity (NEDA) over a three-month period.46
Meanwhile, an analysis of 665 people with MS in Denmark and Switzerland sought to measure real-world discontinuation rates for Tecfidera and determine why patients stop the medication. The average length of Tecfidera use among the study subjects was 15.3 months. The researchers found that 200 patients (30.1% of the study population) discontinued Tecfidera, with 115 of them citing adverse events as the main reason. Lymphopenia (a shortage of an infection-fighting white blood cell), gastrointestinal (GI) discomfort, and flushing were the most common adverse effects reported. Disease activity and pregnancy were also common reasons for discontinuation.
Among those who discontinued Tecfidera within three months after starting treatment, GI discomfort was the most common reason cited. Lymphopenia, GI effects, and disease activity were common reasons among those who stopped after three to 12 months, while lymphopenia and disease activity drove discontinuation after one year.47
Pregnancy is a common reason for stopping Tecfidera and other DMTs, as reflected in the findings from the study just cited. While clinical trials and post-marketing data have not found evidence that exposure to delayed-release Tecfidera during pregnancy poses safety concerns for the mother or unborn child, the medication’s manufacturer advises that the agent may cause fetal harm based on animal studies.4 However, recent research may provide reassurance for women who are weighing the risks and benefits of taking Tecfidera during pregnancy. As noted earlier, women who are pregnant or planning on becoming pregnant, and who are taking or considering a DMT, should consult with their physician.
Researchers reviewed data from an ongoing registry of women with MS who took Tecfidera one day before their last menstrual period, before conception, or during pregnancy. Data were obtained at enrollment, at six to seven months of gestation, at four weeks after estimated delivery date, and at four, 12, and 52 weeks after birth. Mean duration of fetal exposure to dimethyl fumarate was 5.7 weeks.
As of October 2018, a total of 194 births were reported, including 177 live births and 17 fetal deaths (16 miscarriages and one stillbirth). No ectopic or molar pregnancies, nor infant or maternal deaths, occurred. Of the 174 infants for whom gestational age was known, 160 were born full-term and 14 were premature. Of the 144 infants for whom gestational size was recorded, 119 were appropriately sized, 13 were small, and 12 were large. Birth defects were reported among seven (4%) of the 194 births.48