Fingolimod seems to be doing the job. Why can't we have it 1st-line? #ClinicSpeak #MSBlog #MSResearch
"The following paper describes the long term (5-year) extension results of the fingolimod trials. As expected MSers are doing very well with a significant proportion free of clinical and MRI activity. It would be helpful to know how many are NEDA after rebaselining at 12 months. I note that about 1 in 10 of treated subjects withdrew due to adverse events; this is quite high. It would be interesting to know how many withdrawals were due to opportunistic infections the most worrying emerging adverse event with fingolimod. On balance fingolimod seems to have an acceptable benefit:risk profile; it is a great pity we can't use it first-line in Europe. I suspect MSers living in countries where a significant proportion of treated with fingolimod first-line will do better than average than MSers living in countries where access to the drug is second-line. The reason why I say this is that fingolimod is the oral agent with the greatest impact on end-organ damage (brain atrophy). The data that is emerging linking brain atrophy to cognitive impairment and poor outcome in MS is very compelling. Who wouldn't you want to slow your rate of MS-related brain atrophy down and preserve brain? It is a no-brainer!"
Epub: Montalban et al. Long-term results from a phase 2 extension study of fingolimod at high and approved dose in relapsing multiple sclerosis.J Neurol. 2015 Sep 4.
Background: Fingolimod safety and efficacy data in relapsing-remitting multiple sclerosis (RRMS) are available up to 5 years, from an extension of a randomized, placebo-controlled, double-blind, phase 2 study, at a dose higher (5.0/1.25 mg) than the approved dose of 0.5 mg.
Objective: The objective of the study is to present the end-of-study data (>7 years) from the open-label extension of the phase 2 study. In the core phase (6 months), patients (N = 281) were randomized to placebo or fingolimod 1.25/5 mg. In the extension, placebo patients were randomized to fingolimod 1.25/5 mg.
Methods: All patients received open-label 1.25 mg fingolimod after month 24 and 0.5 mg after month 60. Clinical visits were performed every 3 months, expanded disability status scale (EDSS) every 6 months and magnetic resonance imaging (MRI) annually.
Results: 122 (48.8 %) patients completed the extension study; overall fingolimod exposure was 1230.7 patient-years. The most common (>10 %) reasons for study discontinuation were adverse events (19.6 %) and consent withdrawal (16.4 %). Fingolimod treatment for >7 years was associated with sustained low clinical and MRI disease activity. Over 60 % of patients remained relapse free and about 80 % were free from any MRI activity. Overall annualized relapse rate was 0.18. Long-term fingolimod treatment was not associated with new safety concerns.
Conclusions: Long-term fingolimod was well tolerated and associated with a sustained low level of disease activity.