After its approval in May for pediatric MS, the data displayed its efficacy in comparison to standard therapy.
Tanuja Chitnis, MD
Pediatric patients with multiple sclerosis (MS) treated with fingolimod (Gilenya, Novartis) have shown to have lower rates of relapse and less accumulation of MRI lesions over 2 years, compared to interferon ß-1a.
In comparison with interferon ß-1a, the adjusted annualized relapse rate was 0.12 with fingolimod compared to 0.67 (rate ratio, 0.18; 95% CI, 0.11 to 0.30; P <.001) for a relative difference of 82% and an absolute difference of 0.55 relapses (95% CI, 0.36 to 0.74; P <.001).
Additionally, the annualized rate of new or newly enlarged lesions on T2-weighted MRI was 4.39 with fingolimod compared to 9.27 with interferon ß-1a (absolute difference, 4.88 lesions; relative difference, 53%; P <.001).
“This is the first completed registrational, randomized controlled trial for pediatric multiple sclerosis,” lead author Tanuja Chitnis, MD, told NeurologyLive. “The trial investigated the efficacy of fingolimod to interferon ß-1a; the latter is a widely used standard of care in children around the world.”
“Based on this study, fingolimod was approved for pediatric MS by the FDA in May 2018, making it the first drug approved in the US for pediatric MS,” Chitnis added.
In total, the PARADIGMS trial randomized patients with MS under the age of 18 years 1:1 to 0.5 mg fingolimod daily (n = 100) or 30 µg interferon ß-1a weekly (n = 88). Notably, 85.7% of the children in the fingolimod arm were relapse-free over the study duration compared to 38.8% in the interferon-ß-1a group (difference, 46.9 percentage points; unadjusted 95% CI, 33.7 to 60.1).
Chitnis said that in terms of secondary endpoints, fingolimod displayed efficacy in reducing brain atrophy. The rate of brain volume change over the 2-year period was -0.48% with fingolimod compared to -0.80% with interferon (least-squares mean difference, 0.32 percentage points; 95% CI, 0.06 to 0.57).
The number of gadolinium-enhancing lesions per scan up to 24 months was 0.44 with fingolimod and 1.28 with interferon beta-1a (rate ratio, 0.34; unadjusted 95% CI, 0.22 to 0.54).
Additionally, its efficacy in reducing disability progression was exhibited, with fingolimod reducing the risk of 3-month confirmed disability by 77.2% over 2 years compared to interferon (hazard ratio, 0.23; 95% CI, 0.08 to 0.66; P = .015) The Kaplan—Meier estimate of the percentage of patients free from 3-month confirmed disability worsening at month 24 was higher in the fingolimod group than in the interferon ß-1a group (95.2% [95% CI, 91.1 to 99.3] vs. 84.7% [95% CI 77.5 to 91.9]).
“These measures are determinants of long-term disability accrual in patients with MS,” Chitnis noted. She and colleagues noted that the secondary clinical and MRI-related endpoints were significantly different between the groups when post hoc adjustment for multiple comparisons was performed with the use of Bonferroni’s method (adjusted P = .003), though the P values for these endpoints weren’t reported due to a non-prespecified adjustment for multiple comparisons for these outcomes.
Notwithstanding this successful showing from the therapy, the rate of serious adverse events (SAEs) was higher with fingolimod. In the fingolimod group, 16.8% (n = 18) of patients experienced ≥1 SAE, compared to 6.5% (n = 7) in the interferon group. In total, 5 patients (4.7%) and 3 patients (2.8%) in the fingolimod and interferon groups discontinued due to an AE, respectively.
Although, 13 patients discontinued treatment in the interferon group due to an unsatisfactory treatment effect, compared to none with fingolimod. The overall incidence of AEs was 88.8% with fingolimod and 95.3% with interferon ß-1a.
“The overall safety profile in fingolimod was similar to adult studies,” Chitnis said. “Notable is an imbalance in seizures: 6 in fingolimod arm and 1 in the interferon-ß-1a arm. Other SAE’s occurred in 1 to 2 patients, without a consistent pattern. There was one case of second-degree heart block in a patient transitioning from the half dose to full dose of fingolimod, which resolved, and she continued on treatment.”
Chitnis T, Arnold DA, Banwell BL, et al. Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med. 2018;379:1017-1027. doi: 10.1056/NEJMoa1800149.