Delayed access to treatments come at a cost. #MSBlog #MSResearch #ClinicSpeak #OffLabel
“The following study shows time is brain. MSers treated in the FREEDOMS study with placebo for 2 years never catch-up, despite receiving active treatment in years 3 and 4, to MSers who received fingolimod continuously for 4 years. The brain volume lost in the first 2 years on placebo is gone. However, once the placebo-treated MSers were switched to fingolimod in the extension study they did well. Overall fingolimod was well tolerated and no new safety signals were noted in the extension study.”
“This study supports the treatment philosophy or early-effective treatment and time is brain.”
“Please note that fingolimod will be the first licensed oral DMT to come off patent. This means that many MSers across the planet will finally be able to access a licensed DMT at a reasonable price. Before this happens there are other off-label drugs that you can access that have been shown to have an effect in MS. This linked post provides a summary and links to my essential list of off-label DMTs for MSers in resource poor settings.”
Essential off-label DMT list:
Epub: Kappos et al. Long-term effects of fingolimod in multiple sclerosis: The randomized FREEDOMS extension trial. Neurology. 2015 Mar. pii: 10.1212/WNL.0000000000001462.
OBJECTIVE: To assess long-term safety and efficacy of fingolimod in MSers with relapsing-remitting multiple sclerosis (RRMS).
METHODS: MSers completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0-2 (FREEDOMS) and years 2-4 (extension) in the extension ITT population.
RESULTS: Of 1,272 MSers (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo-fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more MSers were free from 3-month CDP (p < 0.05) than in a group comprising all placebo-fingolimod MSers. Within each placebo-fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo-fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported.
CONCLUSION: Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.
OBJECTIVE: To assess long-term safety and efficacy of fingolimod in MSers with relapsing-remitting multiple sclerosis (RRMS).
METHODS: MSers completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0-2 (FREEDOMS) and years 2-4 (extension) in the extension ITT population.
RESULTS: Of 1,272 MSers (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo-fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more MSers were free from 3-month CDP (p < 0.05) than in a group comprising all placebo-fingolimod MSers. Within each placebo-fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo-fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported.
CONCLUSION: Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.
CoI: multiple
How is it possible in this day and age that pharma still do trials with placebo? Likewise how is it possible that neuros still allow people to go on such trials when it is clearly evident that if MSers get no treatment, is not in the best interest as time is brain,
Re: "How is it possible in this day and age that pharma still do trials with placebo?" The FREEDOMS study was done a long time ago, prior to there being any oral therapy available; in that era all new trials were still placebo-controlled. I agree it is difficult to do phase 3 placebo-controlled trials in the current era. Phase 2 trials are different; we still need MSers to volunteer for proof-of-concept studies; these typically last 3-6 months. In addition, the regulatory authorities still require placebo-controlled trials in some circumstances. Finally, in progressive MS we don't have licensed treatment placebo-controlled trials are still the norm.
It seems with a simple Bonferroni correction nothing is significant except ARR.
Is the fingolimod only drug , with well effect in braing atrophy? its best than natalizumab, avonex, alentuzumab, laquinimod, teriflunamide down the risk of brain atrophy, ?'