INDIANAPOLIS -- Discontinuation rates after switching from natalizumab (Tysabri) to dimethyl fumarate (Tecfidera) among multiple sclerosis (MS) patients in the real-world setting were generally similar to those seen in clinical trials, according to two posters presented here.
A single-center study had discontinuation rates of about 26% after 1 year, reported Nasima Afsari, MBBS, of Medstar Georgetown University Hospital in Washington.
"The majority did very well on Tecfidera, which was well-tolerated, with few side effects," Afsari told 乌鸦传媒.
Action Points
- Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- The first study is a postmarketing, multicenter prospective study of 530 RRMS patients who changed treatment from natalizumab to dimethyl fumarate. Interim analysis of 227 patients found lower rates of post-switch dimethyl fumarate discontinuation (17%) than observed in previous two phase III trials DEFINE and CONFIRM. The risk of relapse at 1 year while treated with dimethyl fumarate was 25%, and this risk was significantly lower in patients with natalizumab washout period shorter than 90 days.
- The second study is a retrospective chart review of 87 MS patients treated with natalizumab for at least 12 months, assessing dimethyl fumarate discontinuation rates and reasons. This study showed a discontinuation rate of 26.1% with new relapse being the main reason for stopping the dimethyl fumarate treatment. Similar rate of discontinuation was also found in three previous phase III clinical trials DEFINE, CONFIRM, and RESTORE.
A separate study supported by Biogen, which makes both natalizumab and dimethyl fumarate, found a discontinuation rate slightly lower than seen in trials, at 17% over a mean duration of 3 years.
Both were presented at the Consortium of Multiple Sclerosis Centers meeting.
Neither of the studies assessed the switch from natalizumab to either of the two other oral agents, fingolimod (Gilenya) or teriflunomide (Aubagio), which have been on the market longer and have been studied in other trials. There have been fewer data on the transition from natalizumab to dimethyl fumarate since it came on the market in 2013.
STRATEGY
, of Providence Multiple Sclerosis Center in Portland, Ore., and colleagues conducted the STRATEGY study, an ongoing postmarketing study of 530 relapsing-remitting MS patients who switched from natalizumab to dimethyl fumarate in a real-world clinical setting at 46 sites in the U.S.
At the meeting, they presented an interim analysis of 227 patients, which found that post-switch dimethyl fumarate discontinuation rates were lower than seen in phase III trials DEFINE and CONFIRM, at 17% over 3 years compared with about 30% over 2 years.
They also found that the risk of relapse at 1 year on dimethyl fumarate was 25%.
Cohan and colleagues also conducted an exploratory analysis of 113 patients in order to assess relapse rates after switching between stopping natalizumab and starting dimethyl fumarate.
They found that the risk of relapse 1 year after starting the new therapy was lower in patients who had a washout duration of 90 days or less, compared with those who waited more than 90 days to get back on therapy (16% versus 33%). The annualized relapse rate a year after starting dimethyl fumarate was significantly lower in patients with a shorter washout period (0.181 versus 0.423).
"If you have a longer washout, that gives the disease time to flare up," explained Stephen Krieger, MD, of Mount Sinai Hospital in New York City, who was not involved in the study. "You want to have a shorter washout, and our target is about 1 month."
A Reasonable Choice
Asfari's study looked at charts from 87 patients treated at their center over 2 years, all of whom had been on natalizumab for at least 12 months.
They found a discontinuation rate of 26.4% over 1 year, which was mostly driven by relapse, specifically 9.2% of those who discontinued did so because of a relapse, as measured by new T2- or gadolinium-enhancing lesions on MRI, symptom progression, or lymphopenia.
About 7% of patients discontinued due to drug intolerance, primarily flushing or gastrointestinal symptoms.
Asfari said the results were similar to those seen in the larger phase III DEFINE, CONFIRM, and RESTORE trials, though she noted that the main difference between this real-world experience and DEFINE and CONFIRM was the rate of discontinuation due to relapse or progression.
But she cautioned that the difference could be attributable to small sample size and the fact that patients had high disease activity before they started on natalizumab.
Both groups concluded that their findings suggest dimethyl fumarate seems to be a reasonable choice for patients who stop natalizumab.
Asfari added that because there's little data on which oral agent makes an optimal choice after stopping natalizumab, the choice should be highly individualized. But at her center "our first preference is dimethyl fumarate. If the patient is not of childbearing age, you can consider teriflunomide but, in general, it varies. "In our practice we like dimethyl fumarate because of its safety. It has minor side effects that are very transient and can be adequately controlled."
Disclosures
The STRATEGY study was supported by Biogen.
Cohan disclosed financial relationships with Acorda, Genzyme, Novartis, and Sanofi.
Afsari reported no disclosures.
Primary Source
Consortium of Multiple Sclerosis Centers
Source Reference: Cohan S, et al "Real-world clinical outcomes in relapsing-remitting multiple sclerosis patients who switch from natalizumab to delayed-release dimethyl fumarate: Preliminary analysis of a multicenter, retrospective, observational study (STRATEGY)" CMSC 2015; Abstract DX16.
Secondary Source
Consortium of Multiple Sclerosis Centers
Source Reference: Amjad F, et al "The safety and efficacy of switching from natalizumab to dimethyl fumarate: Real-world experience" CMSC 2015; Abstract DX09.