Background Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.
Methods We randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months with magnetic resonance imaging (MRI) and clinical evaluations (core study, months 0 to 6). The primary end point was the total number of gadolinium-enhanced lesions recorded on T1-weighted MRI at monthly intervals for 6 months. In an extension study in which the investigators and patients remained unaware of the dose assignments (months 7 to 12), patients who received placebo underwent randomization again to one of the fingolimod doses.
Results A total of 255 patients completed the core study. The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0 mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions).
The annualized relapse rate was 0.77 in the placebo group, as compared with 0.35 in the group given 1.25 mg of fingolimod (P=0.009) and 0.36 in the group given 5.0 mg of fingolimod (P=0.01).
For the 227 patients who completed the extension study, the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod, and both measures decreased in patients who switched from placebo to fingolimod.
Adverse events included nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic elevations of alanine aminotransferase levels were more frequent with fingolimod (10 to 12%, vs. 1% in the placebo group).
One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group. Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second.
Conclusions In this proof-of-concept study, fingolimod reduced the number of lesions detected on MRI and clinical disease activity in patients with multiple sclerosis. Evaluation in larger, longer-term studies is warranted.
Mechanism of Action, Potential Clues:
Sphingosine-1-Phosphate (S1P) blocks egress from lymph nodes rather than enhancing migration to them.
Effects on migration: Prevents lymphocyte egress. Tightens endothelial junctions. Direct effects on lymphocytes.
S1P Preferential depletion of naïve T cells. Adoptively transferred in vitro activated, polarized T cells do not deplete with Fingolimod.
- New therapy agent based on old autoimmunity of MS.
- In 1 year period the evaluation of numbers of new lesions and relapses must be considered as not accurate as it shows, means- it proves nothing. Natural Course of MS must be evaluated separately first, and only than you form the group. More, the impressive numbers were shown after 6 months, it is too short.
- There is no information provided on lesions numbers in all groups before trial, so this extrimely valuable information missed.
- We don't know what kind of MS was taken; age of patients, time from onset, etc are also unknown.
-I case of encephalopathy in less than 200 patients (group1 and 2) and in in a period less than 6 months?