For those who doubt the effectiveness of messaging about drug profiles, including the risk of adverse events, diroximel fumarate should ease their minds as a recent survey of MS specialists found almost tw0-thirds in agreement about the GI tolerability of the agent. The findings were first reported at CMSC and described in an article originally published Nov. 4, 2021 and republished as part of BreakingMED’s year-end review of clinical news in 2021. Click here to view the original version and obtain CME/CE credit for the activity.
Most health care professionals who treat patients with multiple sclerosis (MS) thought diroximel fumarate had a better gastrointestinal (GI) tolerability profile than dimethyl fumarate, an analysis of survey data showed.
Of 223 U.S. health care providers who either were, or who worked with, a board-certified neurologist managing 25 or more MS patients, 64% perceived that diroximel fumarate offered better GI tolerability, reported Denise R. Bruen, ANP-BC, MSN, RN, of University of Virginia Neuroscience in Charlottesville.
Most thought diroximel fumarate was either equivalent to or better than dimethyl fumarate in other areas of tolerability (92%), patient satisfaction (90%), patient adherence (92%), overall safety (91%), efficacy (93%), administration or dosing (83%), and ease of treatment initiation (81%), Bruen said at the 2021 Consortium of Multiple Sclerosis Centers annual meeting.
“About 75% of prescribers had diroximel fumarate experience,” Bruen explained in her presentation. “They chose to use [the drug] due to good tolerability, oral dosing, mechanism of action, and reduction in relapses.”
Diroximel fumarate was approved in 2019 for patients with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. It has the same active metabolite as dimethyl fumarate, but its metabolism results in smaller methanol concentrations in the small intestine than dimethyl fumarate, reducing GI adverse effects.
“Diroximel fumarate demonstrated favorable GI tolerability in phase III clinical studies of patients with relapsing-remitting MS; these include a head-to-head study of diroximel fumarate versus dimethyl fumarate,” Bruen noted. Both medications are taken orally.
In their analysis, Bruen and co-authors assessed MS patient-level data collected from health care providers between Jan. 28 and March 1, 2021. Patients included in the study were over 18 years old and diagnosed with MS, treated with a disease-modifying therapy (DMT), switched to a new DMT three months ago or less, and were seen by a neurology health care provider at the most recent visit.
The health care provider completing the survey had to be or work with a board-certified neurologist or MS specialist who was in practice for at least two years but not more than 40 years. The provider needed to spend at least 50% of his or her professional time in clinical practice, and manage at least 25 patients with MS.
Providers were in practice an average of 16 years and spent 92% of their time in clinical practice seeing patients. Most said they currently prescribed diroximel fumarate (69%), 26% had never prescribed it, and 5% had previously prescribed it but had no patients currently taking it.
Data were available for 1,221 MS patients with mean age of 42. Most patients (68%) were women, and 70% were White. Overall, there were 178 charts for patients who recently switched to diroximel fumarate (129 with relapsing-remitting MS, 22 with clinically isolated syndrome, nine with primary progressive MS, and 18 with secondary progressive MS). Only those switches performed by the data-entering provider (166 switches) were included in the analysis.
Among patients who switched to diroximel fumarate, the most common previous treatments were dimethyl fumarate (30%), interferons (25%), and glatiramer acetate (25%). Time on a previous treatment ranged from 1 month to 38.5 months.
Reasons providers gave for switching patients from the previous treatment to diroximel fumarate included:
- Efficacy (52%; primary reason 37%).
- Tolerability (49%; primary reason 29%).
- Patient request (25%; primary reason 8%).
- Safety (22%; primary reason 5%).
- Insurance (17%; primary reason 8%).
Among recently switched patients who had been under the care of the provider for at least the past 12 months, those who switched to diroximel fumarate (n=105) had higher disease activity in the year prior to DMT switch than patients who switched to other treatments (n=658).
Earlier research, including the EVOLVE-MS-1 and EVOLVE-MS-2 studies, has shown GI and other benefits for diroximel fumarate. Interim data from EVOLVE-MS-1 in 2020 included data on 696 patients treated with diroximel fumarate. Adverse events occurred in about 85% (mild 31.2%, moderate 46.8%), with treatment discontinuation of 14.9%. Discontinuation due to adverse events occurred in 6.3% with <1% related to GI events. The analysis also reported a reduction in enhancing lesions and an adjusted annualized relapse rate of 0.16.
EVOLVE-MS-2 was a five-week study comparing bioequivalent doses of diroximel fumarate 462 mg and dimethyl fumarate 240 mg, both twice daily, in patients with relapsing remitting MS. A reduction of 46% in days with more intense GI symptoms was reported for patients treated with diroximel fumarate versus dimethyl fumarate. Overall rates of GI events of 35% versus 49% were seen for diroximel fumarate and dimethyl fumarate, respectively. Discontinuations for adverse events for diroximel fumarate and dimethyl fumarate were 1.6% and 5.6%, with discontinuation for GI events 0.8% versus 4.8%, respectively.
Paul Smyth, MD, Contributing Writer, BreakingMED™
This study was supported by Biogen.
Bruen is a consultant for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Greenwich, Janssen, Novartis, and Sanofi-Genzyme.
Cat ID: 36
Topic ID: 82,36,730,36,764,192,925,763