Efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis: a systematic comparison.

Freedman MS, Hughes B, Mikol DD, Bennett R, Cuffel B, Divan V, LaVallee N, Al-Sabbagh A.
Department of Medicine (Neurology), University of Ottawa, Ottawa, Ontario, Canada. mfreedman@ottawahospital.on.ca

The treatment of relapsing-remitting multiple sclerosis (RRMS) has become more effective over the last decade with the advent of the currently available disease-modifying therapies (DMTs). Pivotal clinical studies differ in many characteristics, such that cross-comparisons of relative risk reductions are of limited value and can be misleading.

Our objective was to compare the clinical efficacy of currently approved first-line DMTs in patients with RRMS, applying an evidence-based medicine approach. We reviewed all phase III pivotal trials of DMTs. Six clinical trials of Avonex, Betaseron, Copaxone, Rebif and Tysabri in patients with RRMS were identified for analysis. Only randomized, placebo-controlled, double-blind studies were included. The clinical efficacy endpoints compared were: proportion of relapse-free patients at 1 and 2 years; annualized relapse rate at 2 years; proportion of progression-free patients at 2 years, and proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months.

Based on these analyses, Betaseron, Rebif, and Tysabri show comparable effects, whereas for several endpoints Avonex or Copaxone did not significantly differ from placebo. In the absence of head-to-head studies for all products used to treat RRMS, it still may be possible to compare treatment effects by applying evidence-based medicine principles. (c) 2008 S. Karger AG, Basel.

PMID: 18437041 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/18437041

Cherie

Great...now I'll have switch to something that gives me the Interferon Flu.

It would explain all the funky annoying MS symptoms I've been having since starting the C. Numb toes, feet, legs, fingers...more ON symptoms, and spasticity.

I was on Copaxone first and it was not effective for me. I switched to Beta and it has worked well. Last MRI showed no new lesions and the ones I had before that were enhanced were not this time. I'm still having symptoms, though, and the numbness in my right hand/arm will not go away.

Erin, the flu like side effects are only temporary (for most people) and you titrate up to a full dose so as not to have too many flu like reactions. As long as I pre-medicated with Motrin before the shot and then again about 4 hours afterwards I was fine. I'm on a full dose now and only pre-medicate. I don't have to take anything afterwards.

Not having that awful welt-like site reaction and the itching was a blessed relief. And....only having to take the shot every other day is nice, too.

Erin, I am on Rebif, about the 8th wk., and have never had any fluish side effects and have dropped all but one coated aspirin pre-med.

Cherie, thanks for the post, and thanks for the wealth of information you share here.

Thank you for this Cherie. One of my favorite things about you is that even though you don't use a DMD at this point you don't discredit them and are willing to share new information that you come across. Thank you.
Jules

P.S. with regard to this study, and I will get a copy of the full text before I make my final decision, for the most part my personal opinion is that I am very skeptical of all the MS studies that don't last for more than a couple of years.

This disease can move pretty slowly but that doesn't doesn't mean that at some point it won't change its course. My optimism is always haunted by the folks that did wonderfully for 20 years and then really declined quickly. No rhyme or reason.

Has Rebif been having the same problem with dull needles that the Copaxone has been having lately?

I hurt my right shoulder the other day, and couldnt use my right arm to do the shot on my right side, so I had my dad give me my shot of C last night...got a really dull needle. OMG! It felt like he was stabbing me with a dull steak knife! Almost as painful as using the autoject and a dull needle. Owwwwie!

The dull needles are what are making me consider switching over to something new.

Cherie, your post prompted my post about looking at the clinical trial site again.

I'm of the school of thought . . . "whatever works".

It is hard to filter to the various pieces of information we have access to, and to then to validate them in any useful way. The way I understood this particular article though was that it was just an analysis of existing information/studies, validated by a specific protocol. The information they relied upon was only:

- phase III pivotal trials
- patients with RRMS
- existing randomized, placebo-controlled, double-blind studies

The clinical efficacy endpoints compared were:

- proportion of relapse-free patients at 1 and 2 years
- annualized relapse rate at 2 years
- proportion of progression-free patients at 2 years
- proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months.

I'm not sure why they picked gad-enhancing lesions at 1 yr and 9 mo, but perhaps that information wasn't comparable or available for the entire two years in all the trials (or ?). It would be good to read the copy of the full text, if you happen across it. (Personally, I don't give much merit to the evaluation of gad-enhancing lesions anyway )

I remember reading about the analysis tool; "evidence-based medicine principles", but I didn't happen to retain this information. Hopefully it's a good tool for making a comparison, but I don't know that either.

I think it is really quite common that many of us turn a corner at 20 yrs actually. They say that 50% of those with RRMS will be SPMS at the 10 yr mark, and 90% of us at the 20 yr mark. Mind you, this is old statistics (pre-DMT's), so perhaps things will shift in the coming years.


Ms Trial Lady . . . always looking for her next fix. Thanks for keeping on top of that information. I'm always looking for something that might be more agreeable too, then what we currently have available. I'm glad so many of us can take the drugs we have though, in the meantime.

Cherie

I was dx'd in 2001 so I am wondering if that stat will hold true. I always seem to be in the 1% group...a shift in this stat would be seem reasonable given the new medication as well as more reliable diagnostic tools. Just a thought.




always looking, yes. I guess it's that philosophy I live by, if you're not living on the edge, you're taking up too much room!

Yes, new diagnostic tools means many of us are probably dx a lot quicker then we used to be. Good point ... and that alone could shift the length of time till SPMS.

As far as the DMT's (and/or other alternative treatments, like LDN maybe), I would think they might affect the amount of time before SPMS, at least FOR THOSE THEY WORK FOR. The trick is to find one that works for us as individuals though.

I know I was 'borderline' SPMS after 14yrs, but then I started on LDN and they left me categorized at RRMS. I suspect I may either be headed into SPMS now, or maybe I just left that infection too long last year and caused some "permanent" damage (that makes it appear/feel as though I have advanced with the disease). I'm still having relapses, but most people with SPMS do in the beginning of that phase. My EDSS has not changed though, so at least that's good news.

I'm 17+ - 29 yrs (if I include the undx time, with symptoms) into this journey.

Time will tell.

Cherie