PARADIGMS Trial May Favor the Use of Oral Pill in Pediatric Multiple Sclerosis

The oral pill fingolimod has considerably reduced relapses vs interferon beta-1a in PARADIGMS. This was the first controlled trial of fingolimod vs. interferon beta-1a in pediatric multiple sclerosis. The good news has been reinstated through the fact that the reduction has been around 82% in the annualized relapse rate or ARR in the group of fingolimod vs. interferon (0.67 vs. 0.12; p<0.001). This annualized relapse rate reduction between the fingolimod and interferon group offers a significant benefit on MRI markers of disability and disease.

Pediatric patients who have been on MRI had been treated with fingolimod which has shown that patients had gone through 53% relative reduction in T2 lesions. Another group had gone through 66% relative reduction in gadolinium-enhancing lesions. This second group was treated with both to which the above results were found. However, not all is good with fingolimod as mentioned by Dr. Tanuja Chitnis from the Brigham & Women’s Hospital in Boston, Massachusetts, US. Fingolimod has come with some dangerous adverse effects which is a matter of concern for the investigators.

What is the Story Behind?

Pediatric patients usually face more relapses and are prone to physical disability at an earlier age than those diagnosed during their adulthood. Around 3-5% of pediatric patients start suffering from the relapse right from the onset of childhood. However, the more alarming fact is that there are very few controlled clinical trials in children with disease-modifying therapies which are resulting in treatments that are less effective. These treatments are adult therapies with nothing geared towards children thus making them arbitrary. However, these are being approved by medical associations in absence of anything targeted towards children primarily.

PARADIGM study involved 215 children and adolescents which were primarily in the age group of 15 years. The Expanded Disability Status Scale or EDSS and relapsing-remitting MS score was 1.5 which was randomized to oral fingolimod for up to 0.5mg. This dose was adjusted according to body weight and the duration of the study was up to 2 years. In the end of the course duration, the secondary endpoint of time to the first relapse was delayed with the application of fingolimod. It is to be noted that around 86% of pediatric patients on fingolimod were free of relapse whereas only 39% of those on interferon were free of relapse at 2 years. It is obvious that the result with fingolimod was much better.

Not just this; fingolimod performed in a better way at reducing the annual rate of brain atrophy vs. interferon (-0.48 vs. -0.80; p=0.014). Moreover, fingolimod also delayed the time to 3-month confirmed disability progression. Whereas 85% of patients were free from confirmed disability by administering interferon, the rate was 95% with the administration of fingolimod. However, the adverse effect was also higher with fingolimod which involved seizures also. 2% of patients were also struck by leucopenia. Experts are of the view that fingolimod is generally favorable for pediatric patients with mostly good results and a few adverse effects. It is generally effective given the fact that it underwent the first controlled study.

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