Two strikes your out….Prozac doesn’t make the cut in Progressive MS…Again

T

Fluoxetine in progressive multiple sclerosis: The FLUOX-PMS trial.

Cambron M, Mostert J, D’Hooghe M, Nagels G, Willekens B, Debruyne J, Algoed L, Verhagen W, Hupperts R, Heersema D, De Keyser J; FLUOX-PMS Study Group. Mult Scler. 2019 Jun 20:1352458519843051. 

BACKGROUND: Preclinical studies suggest that fluoxetine has neuroprotective properties that might reduce axonal degeneration in multiple sclerosis (MS).

OBJECTIVE:To determine whether fluoxetine slows accumulation of disability in progressive MS.

METHODS: In a double-blind multicenter phase 2 trial, patients with primary or secondary progressive MS were randomized to fluoxetine 40 mg/day or placebo for a period of 108 weeks. Clinical assessments were performed every 12 weeks by trained study nurses who visited the patients at their home. The primary outcome was the time to a 12-week confirmed 20% increase in the Timed 25 Foot Walk or 9-Hole Peg test. Secondary outcomes included the Hauser ambulation index, cognitive tests, fatigue, and brain magnetic resonance imaging (MRI).

RESULTS: In the efficacy analysis, 69 patients received fluoxetine and 68 patients received placebo. Using the log-rank test (p = 0.258) and Cox regression analysis (p = 0.253), we found no significant difference in the primary outcome between the two groups. Due to an unexpected slow rate of progression in the placebo group, there was insufficient statistical power to detect a potential benefit of fluoxetine. We found no differences between the two groups for secondary outcomes.

CONCLUSION:The trial failed to demonstrate a neuroprotective effect of fluoxetine in patients with progressive MS.

We have heard of this study already because the design was already published. But just like Buses when you have been waiting for one to come along you get two one after the other. This is the first one that was presented at ECTRIMS about 2 years ago and the take home message is it failed…..But did it ?

Fluoxetine in progressive multiple sclerosis (FLUOX-PMS): study protocol for a randomized controlled trial. Cambron M, Mostert J, Haentjens P, D’Hooghe M, Nagels G, Willekens B, Heersema D, Debruyne J, Van Hecke W, Algoed L, De Klippel N, Fosselle E, Laureys G, Merckx H, Van Wijmeersch B, Vanopdenbosch L, Verhagen W, Hupperts R, Hengstman G, Michiels V, Van Merhaegen-Wieleman A, De Keyser J. Trials. 2014 Jan 25;15:37. doi: 10.1186/1745-6215-15-37.

The effect of fluoxetine on progression in progressive multiple sclerosis: a double-blind, randomized, placebo-controlled trial. Mostert J, Heersema T, Mahajan M, Van Der Grond J, Van Buchem MA, De Keyser J. ISRN Neurol. 2013 Jul 29;2013:370943.

We will never know because the second one came along at ECTRIMS last year and that failed too..

So prozac (fluoxitine) is not going to be of value, probably. That is a shame, but if we don’t try we can’t succeed.

However, people with progressive MS have been waiting for studies for so long that there was a great placebo effect by going into a trial. As a consequence people did not progresess as fast expected and so there was no conclusion to be made……So we learn little except that academic trials are often horribly underpowered to get an answer. people did not progress as quickly as thought and years of effort wasted. Maybe if they had kept recruting until they had enough events to make an informative choice…this would not have been wasted effort. But these studies have cost mplications

So effective trial design is key for finding agents that work. This study could never work because there was not enough people in the trial. I have been saying this for so long that I look like a SMURF.

Don’t understand?. I have said this so many times that I am “blue in the face” because of not breathing whilst talking.

MS_SMART came along , three drugs against placebo, all failed. Were they all rubbish? or was the trial design wrong?

What do we do next…..a pertinent question…Same again but with a different drug choice? or Target Biology and get rid of what you know you can get rid of and then try control the unknown.

Have a DMT on the bottom rung.

About the author

MouseDoctor

6 comments

  • Not your fault MD – my comment is for the wider MS research community.

    “The definition of insanity is doing the same thing over and over again, but expecting different results.”

    I posted the other day that I was bored of MS research – idea for study, fundraising, raising hope, study takes forever, study fails.. on to next idea.

    I would like the MS research community to be honest – they haven’t got a clue what causes the destruction of brain cells in MS. I’ve lost track of the have a punt studies which try out a drug in the hope it has some effect (and it never does). I predict the statin trial will not be successful. And it will fail because of poor study design, underpowered, wrong dosage……

    At least Barts stick their heads above the parapet and provide transparency about their trial / future trials. In the U.K. we have MS research centres in London (UCL, Imperial), Oxford, Cambridge, Bristol, Plymouth, Edinburgh, Glasgow. I have to ask the question – what the hell are they working on? The MS Society lists out all the research grants it has made, but I don’t see any results that are contributing to new treatments or benefitting people with MS. In the last 5 years or so, we Lemtrada and Ocreluzimab are the only treatments which have been licensed which can be classed as advances on earlier treatments. Will we see any breakthroughs at ECTRIMS – I doubt it. Please prove me wrong someone,

  • A DMT on the bottom rung for progressive MS… That should be targetting the inflammation associated with progressive MS, which is different. We don’t have that either.

  • Question is how they got funding if the trial was underpowered. When I was doing research, a while ago I admit, funding criteria were pretty tight. Is it becoming more about people’s CVs than research of real value. For me, it’s about time the whole system needs a shake up. A 19th century system is maybe not appropriate in the 21st?

  • What is causing so many MS studies to be underpowered? Is it funding, poor study design (if so, why are ethics approving it), or poor study management? The problem with this is you just can’t definitively assess the strength of the null hypothesis. Then some bright spark determines their is a trend in the data and runs another study. Why not do it the right way once???

    This issue seems to be magnified in MS research when compared to their fields like oncology for example. Is it because the studies are Investigator lead rather than Industry (who have the budget to withstand recruitment delays)?

  • Subtle Symptoms Of Multiple Sclerosis You Should Never Ignore, One of the benign symptoms that we tend to forget about are vision related problems. This is not an issue that is commonly associated with MS but it should be. Some patients may experience double vision and other patients may experience blurred vision. Numbness is experienced by those who have multiple sclerosis as well because of the effect that this disorder has on the entire nervous system.

    https://youtu.be/-2K8JMv3aHs

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives