Most children and adolescents with pediatric-onset multiple sclerosis (POMS), especially those treated intravenously with a disease-modifying therapy (DMT), achieve no evidence of disease activity within two years of diagnosis, according to a real-life study from the U.S.
Patients whose DMTs are infused into a vein (intravenous treatment) are more likely to reach disease activity-free status than are those on other DMTs or no DMT, suggesting this treatment route be a favored option for the pediatric MS population.
The research, “Assessing No Evidence of Disease Activity in Pediatric Onset Multiple Sclerosis,” was presented by Jenny Feng, MD, with the Cleveland Clinic’s Mellen Center for MS Treatment and Research, at the MSVirtual2020 held Sept. 11–13. It marked the 8th joint meeting of the American (ACTRIMS) and European (ECTRIMS) Committees for Treatment and Research in MS.
Around 10,000 children worldwide are estimated to have POMS, accounting for 5%–10% of all multiple sclerosis (MS) cases. These children are usually treated with therapies approved for adults with MS, but only one DMT — oral Gilenya (fingolimod, by Novartis) — is approved in the U.S. for MS patients starting at age 10.
Treatment decisions in POMS patients are challenging, due to limited clinical trial efficacy data on available MS therapies, and a lack of clear optimal treatment goals for this patient population.
No evidence of disease activity, or NEDA — a status defined by the absence of relapses, new or enlarging brain lesions (as assessed with MRI), and confirmed disability progression (as evaluated by the expanded disability status scale) — has been proposed as a possible outcome measure and treatment goal in MS.
However, NEDA rates and the factors that may influence its achievement in POMS patients are still unknown.
Researchers at Cleveland Clinic and the University of Utah set out to determine the proportion of POMS patients achieving NEDA, and predictors of NEDA status in a real-world setting.
They retrospectively analyzed data from 913 children and adolescents with POMS available through the Pediatric Multiple Sclerosis and other Demyelinating Diseases (PeMSDD) database.
Sponsored by the U.S. Network of Pediatric MS Centers and the National Multiple Sclerosis Society, this database collects information on youth with MS and other demyelinating diseases to better understand the cause and early detection of these disorders in children, as well as to inform clinical trial design.
The team analyzed the proportion of patients achieving NEDA at 12, 18, and 24 months post-diagnosis, and compared demographic and clinical data between patients achieving NEDA (NEDA group) with those still showing evidence of disease activity (EDA group).
Results showed that over 74% of patients were not on any DMT with the first six months of diagnosis. Still, data indicated that 56.2% of this patient cohort achieved NEDA after one year, 62.1% at one and a half years (18 months), and 68.4% after two years.
They show a majority of POMS patients achieving NEDA at some point within two years after diagnosis, despite most not being given any DMT in the first six months.
This high NEDA rate is consistent with previous data on POMS patients receiving Gilenya (58% achieving NEDA) or Biogen’s Tysabri (58%–80%), Feng said.
She also suggested that the rise over time in the proportion of patients reaching NEDA may be associated with a time lag between treatment initiation and its clinical effects, and/or with the delay in DMT initiation.
An analysis of predictive factors for NEDA found no significant differences in terms of demographic and clinical features between patients attaining disease activity-free status and those who did not.
However, among patients on a DMT, intravenous treatments were more common in the NEDA group than in the EDA group. Those on an intravenous DMT were more likely to achieve NEDA at all time points than patients on an oral or injectable DMT or no DMT.
Intravenous DMTs for MS include Tysabri, Ocrevus (by Genentech), and off-label rituximab (sold as Rituxan by Genentech and Biogen in the U.S., and as MabThera by Roche in Europe).
At later time points, 18 and 24 months, recent DMT use was a stronger predictor of NEDA status than initial DMT use (first six months), suggesting that NEDA is an achievable target even for those who switch therapy, the researchers stated.
Notably, the likelihood of achieving NEDA for those recently on an intravenous DMT was two times greater than that of patients on no DMT.
“Patients on infusion DMT were more likely to achieve NEDA compared to other or no DMT,” Feng said.
Researchers also found evidence that an absence of confirmed disease progression was not a relevant criteria to include in the NEDA definition for this pediatric patient population, due to these patients’ better relapse recovery and lesser sustained disability.
Cognitive function may be a more useful criteria instead, Feng noted.
“Cognition may be a more sensitive outcome measure to include in NEDA,” she said, adding that this might be the future direction of POMS studies.
