Using highly effective DMTs early linked to fewer relapses in children

Children and adolescents with multiple sclerosis (MS) who receive high-efficacy disease-modifying therapies (DMTs) early on are significantly less likely to experience a relapse than those given a less efficacious drug, a real-world study found.

While most patients on moderate-efficacy therapies eventually switched to a more effective one, a delayed start of high-efficacy therapy was less effective than initiating these drugs from the outset, researchers noted.

“Our study suggests that rapid initiation of more aggressive treatment shortly after the diagnosis may allow better disease control in [pediatric-onset MS],” the researchers wrote.

The study, “Early Use of High Efficacy Therapies in Pediatric Forms of Relapsing-remitting Multiple Sclerosis: A Real-life Observational Study,” was published in Multiple Sclerosis and Related Disorders.

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While MS mostly developed in adults of childbearing age, about 10% of cases happen in children and adolescents. These pediatric patients usually have relapsing-remitting MS (RRMS), a form of the disease marked by relapses when symptoms worsen, interspersed with periods of remission when symptoms improve or go away.

RRMS also is the most common MS type in adults, but children and adolescents with MS tend to have more frequent relapses, more MRI disease activity, and worse cognitive function.

These younger patients usually are first treated with a moderate-efficacy DMT and eventually can switch to a more effective drug if they’re responding poorly to treatment. However, there’s growing evidence that most patients will require this escalation in treatment and that it may be best to use a high-efficacy DMT early on.

Research team in France

To evaluate the efficacy of moderate- and high-efficacy drugs in a real-world clinical setting, a team of researchers in France examined data from 64 children and adolescents diagnosed at four hospitals over a decade.

The study included 51 girls and 13 boys, with a mean age 15.5, who started treatment a median of one year after their first symptoms. About one-third (36%) had experienced at least one relapse before the start of treatment and two-thirds (66%) had at least one active, inflammatory brain lesion.

The majority of patients (52 patients) started with moderate-efficacy DMTs, which included interferon-based medications (46%), dimethyl fumarate (sold as Tecfidera and generics, 35%), teriflunomide (sold as Aubagio and generics,  13%), and glatiramer acetate (marketed as Copaxone and others).

Of the 12 patients who were started on a high-efficacy DMT, 75% were on Tysabri (natalizumab) and 25% on fingolimod (sold as Gilenya and also available as generics).

Gilenya is indicated for the treatment of children and adolescents ages 10 and older in both the U.S. and Europe. Aubagio also is approved for pediatric patients in Europe. Other medications often are used off-label in this population.

Among patients who started with a moderate-efficacy DMT, the chance of sticking with it over time was low — about 10.2% were still on these therapies after a median follow-up of 22.5 months.

Most of them switched to a high-efficacy DMT after a median 28.5 months, or about 2.4 years. The most common drug chosen for the switch was fingolimod (50%), followed by Tysabri (37%), Ocrevus (ocrelizumab, 10%), and Lemtrada (alemtuzumab, 3%).

Most eventually switched to high-efficacy DMTs

“Most patients on [moderate-efficacy DMTs] finally switched to [a high-efficacy DMT], which highlights the lack of efficacy of [moderate-efficacy DMTs] in this pediatric population,” the researchers wrote.

Results showed that 52% of patients experienced at least one relapse over the follow-up period. However, significantly more patients who received a less-effective drug from the start experienced at least one relapse (62%), compared with those given a highly effective DMT early on (8.2%).

Put another way, patients on a moderate-efficacy DMT experienced about 10 times more relapses per year than on a more effective therapy (0.232 vs. 0.0238 relapses per year).

Consistently, patients with a more effective first-line therapy were significantly more likely to reach the 6.5 year mark without experiencing any relapses — 90.9% probability, compared with 23.3% for those on a moderately effective drug.

There also was a tendency for patients on the moderate-efficacy DMTs to experience disability worsening (7.8% vs. 0%), but the results failed to reach statistical significance. “This might be due to the short follow-up period in our study, and a lack of statistical power due to small sample size,” the researchers wrote.

The research team also conducted some exploratory analyses in which it compared patients in three groups: those on high-efficacy drugs from the start, those always on moderate-efficacy DMTs during follow-up, and patients who started on a moderately effective drug and switched to a more effective one.

Their findings revealed that patients who were on a high-efficacy DMT from the beginning also had greater likelihood of remaining relapse-free compared with those who switched to a more effective drug within two years (100% vs. 63.5%).

“Delayed initiation of high efficacy therapy did not make it possible to catch up,” the team wrote.

However, patients who switched had better outcomes than those who remained on moderate-efficacy therapies for more than two years, a group in which no patient remained relapse-free over follow-up.

Evidence favors more aggressive approach

“Our results add to the cumulative evidence that favors a more aggressive therapeutic strategy in [pediatric-onset MS]: the earlier the [high-efficacy DMT] was introduced, the greater the probability of being relapse-free,” the researchers concluded.

“These results suggest an interest in treating immediately with [a high-efficacy DMT], and this must be confirmed by other studies,” they added.