STOCKHOLM — Patients with pediatric multiple sclerosis (MS) treated with newer medications experienced fewer relapses, fewer new or enlarging T2 lesions, and a lower risk for developing gadolinium-enhancing lesions during follow-up compared with standard injectable treatments, a large multicenter study found.
Participants started one of several newer disease-modifying therapies (DMT), for example, experienced a significantly lower relapse rate compared to others started on an injectable therapy, with a rate ratio of 0.45 in an analysis adjusted for propensity scores.
"We found that initial treatment with newer disease-modifying therapies — such as dimethyl fumarate, fingolimod, natalizumab, and rituximab — led to better control of relapses and MRI disease activity than injectables — glatiramer acetate and interferon-betas — in children with MS," lead author Kristen Krysko, MD, MS clinical research fellow, Department of Neurology at the University of California San Francisco, told Medscape Medical News.
"This suggests that these newer treatments should be used earlier in the course of disease in pediatric MS," she added, "although long-term safety data is needed to understand the safety of this approach in children."
The findings were presented here at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019.
Multiple Clinical Challenges
The conventional strategy to treat MS in this age group is to start with injectable agents and then escalate therapy to address breakthrough disease. "Others, however, have promoted use of highly effective therapy early in pediatric MS," Krysko said.
"Data is not really available regarding which therapy to use first," she added. Such information is critical because "pediatric MS has the potential for long-term disability."
To compare the relative efficacy of different DMT types, Krysko and colleagues conducted an observational cohort study at 12 regional pediatric MS centers across the United States. They compared outcomes among 197 participants taking a new DMT as initial therapy to another 544 participants receiving an injectable.
The relapse rate was the primary outcome. The propensity-score adjusted relapse rate was 0.2 in the newer DMT group compared with 0.5 among participants in the injectables group. In addition, the number needed to treat with newer DMTs to prevent relapse was 3.70 patients.
Secondary outcomes included imaging findings. For example, development of new or enlarging T2 hyperintense lesions also favored the newer DMT group (adjusted hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.37 - 0.73).
In addition, the median time to develop a new lesion was 2.79 years in the newer DMT group vs 0.42 years in the injectable group.
The newer DMTs were also associated with a lower risk for developing gadolinium-enhancing lesions compared with the injectable agents (adjusted HR, 0.38; 95% CI, 0.23 - 0.62).
The median time for participants to develop a new gadolinium-enhancing lesion was not yet reached in the newer DMT group, but it was 2.25 years among participants receiving an injectable.
"Initial treatment of pediatric multiple sclerosis or clinically isolated syndrome with newer DMTs led to better disease activity control compared to injectables," Krysko said.
The researchers computed propensity scores using logistic regression to predict newer DMT use, including pre-identified confounders. These confounders included sex, race, ethnicity, site, age at onset and first DMT, first event characteristics, height, weight, diagnosis, number of relapses in prior 6 months, new T2 hyperintense or gadolinium enhancing lesions in prior 6 months, and baseline EDSS.
Strengths of the study include a large cohort of children, prospective data collection, and "robust" statistical methods, Krysko added. An inability to separate individuals' DMTs was a limitation.
A meeting attendee asked about controlling for adherence with injectable agents. "We did not have adherence data in the database, so it's a limitation. In the real world, that is what happens, so it reflects real-world experience," Krysko replied.
"It is a very important study with a large number of patients," session comoderator Jorge Correale, MD, of the Department of Neurology, Raúl Carrea Institute for Neurological Research, Buenos Aires, Argentina, told Medscape Medical News when asked to comment.
Evaluating this many patients with MS is impressive because "this condition is really rather rare" in that age group, session comoderator Hanne Harbo, MD, PhD, professor and senior consultant, Department of Neurology, Oslo University Hospital in Norway also told Medscape Medical News.
"For my pediatric patients, I would like to see some safety data," Correale said. "She included that this is needed," Harbo added.
When Correale asked directly about safety during the Q&A, Krysko replied, "We did not see anything new versus adults" evaluated in previous research. "It looks like side effects and safety are similar to adults. But we don't have long-term trials."
The study was funded by the National Multiple Sclerosis Society (NMSS). Krysko was supported by a NMSS Sylvia Lawry award and a Biogen MS fellow grant. Correale and Harbo have disclosed no relevant financial relationships.
35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract #249. Presented September 12, 2019.
Medscape Medical News © 2019
Cite this: Damian McNamara. Newer MS Therapies Superior to Injectables in Children - Medscape - Sep 13, 2019.