Frau J, Sormani MP, Signori A, Realmuto S, Baroncini D, Annovazzi P, Signoriello E, Maniscalco G, La Gioia S, Cordioli C, Frigeni B, Rasia S, Fenu G, Grasso R, Sartori A, Lanzillo R, Stromillo ML, Rossi S, Forci B, Cocco E; i-MuST study group. Eur J Neurol. 2018 May 31. doi: 10.1111/ene.13694. [Epub ahead of print]
There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself, or if it is due to the natural course of highly active multiple sclerosis (MS).
Patients with relapsing-remitting MS (RRMS) who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis.
A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Among these patients, 5 (5%) had a reactivation that was considered to be a rebound.
The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound that we found is lower than that which has been previously described.
Rebound or relapse? Rebound is a scary word as it implies a damaging attack after you stop the drug. However, is it simply disease reactivation.? This sounds better from a company perspective, but the fact that 25% of people relapse after stopping fingolimod says that we need to think about how we transition people onto other treatments.
Likewise, before you start a treatment it is worth thinking about what you will do when you stop the treatment. This may help you think about what treatment to start. For example, we have a suggestion/concern that fingolimod may block the activity of alemtuzumab. This idea has yet to be refuted and we can make a biological case of why this could occur.
However, we need to remember that fingolimod is a better option than some MS treatments. This is shown in studies in childhood MS,
Disease activity differs in young patients with multiple sclerosis (MS) compared with the overall adult MS population.
The objective of this paper is to evaluate the effect of fingolimod 0.5 mg on disease activity in young adults with MS from three randomized, double-blind Phase 3 trials.
Annualized relapse rate (ARR), number of new/newly enlarging T2 lesions (neT2), and no evidence of disease activity (NEDA-3) were estimated in the intent-to-treat population at age 20 (youngest) and 30 (young) and compared to the overall population. Models used included a negative binomial regression (ARR/neT2) and a logistic regression (NEDA), with age at baseline as a continuous covariate.
ARRs were higher in younger patients (all p < 0.05), and significantly reduced with fingolimod versus placebo or interferon beta-1a (IFN β-1a), with the percentage reduction inversely proportional to age. Fingolimod was significantly associated with a lower number of neT2 lesions versus placebo/IFN in all age groups except versus IFN in the youngest patients. Regardless of age, fingolimod-treated patients were more likely to achieve NEDA-3 versus placebo/IFN β-1a, with strongest benefits in the youngest patients (all p < 0.05).
Young adults show higher levels of MS disease activity, and may particularly benefit from fingolimod treatment compared with the overall study population.