Wednesday, 14 November 2012

Disease-activity on IFN-beta predicts poor long-term outcome

Bermel et al. Predictors of long-term outcome in MS patients treated with interferon beta. Ann Neurol; 2012: DOI: 10.1002/ana.23758

Objective: To identify early predictors of long-term outcomes in MSers with RRMS treated with IM interferon beta-1a (IM IFNβ-1a).

Methods: Multi-center, observational, 15-year follow-up study of MSers who completed =2 years in the pivotal trial of IM IFNß-1a for RRMS. 136 MSers participated in the 15-year follow-up (69 originally randomized to IM IFNβ-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: 2 or more gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 MRI; 3 or more new T2 lesions on year 2 MRI compared to baseline; and 2 or more relapses over two years. Odds ratios were calculated for early disease activity predicting severe EDSS worsening (worst quartile of change, > 4.5 EDSS points) during the 15-year interval.

Results: The proportion of MSers experiencing early disease activity was lower in patients on IM IFNβ-1a than placebo for all disease activity markers (range 23.5%-29.0% vs. 41.0%-45.5%). In the IM IFNβ-1a group, persistent disease activity predicted severe EDSS worsening: gad lesions (OR=8.96, p<0.001); relapses (OR=4.44, p=0.010); and new T2 lesions (OR=2.90, p=0.080). In placebo MSers, early disease activity was not as strongly associated with long-term outcomes (OR range=1.53-2.62, p=0.069-0.408).

Interpretation: Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ treated MSers with MRI, and for changing therapy in patients with active disease.

"Disease is another data set supporting DMT treatment and the suppression of all measurable disease activity and supports the concept of treating to a target of DAF or disease activity free. Are you disease activity free. If you have not completed our survey on this issue please do. Thanks."

Other posts on this issue you may find interesting

20 Sep 2012
I would therefore appreciate it if you could help by completing the following survey, which will take less than a minute, to see if if you have been exposed to the "disease-activity free " concept in clinic. Please note that all ...
29 Sep 2012
why would any doctor not want their patients to free of disease activity? Surely you start patients on a first line thrapy and them monitor them e.g. MRI, clinical examination. If their is disease activity e.g. MRI shos inflammation, ...
23 Sep 2012
The meeting went well and the preliminary results of the disease-activity free (DAF) survey were very helpful to illustrate the point that concept of disease-activity free (DAF) status has yet to diffuse into clinical practice.
23 Sep 2012
The meeting went well and the preliminary results of the disease-activity free (DAF) survey were very helpful to illustrate the point that concept of disease-activity free (DAF) status has yet to diffuse into clinical practice.


  1. This is the most depressing thing I've read in a while.

    Do treatment changes after the 2-year trial matter?
    For example, what of the patients who perhaps switched to three times a week interferon later, or who switched to Tysabri when it became available? Was their long-term EDSS as bad as the rest of the trial non-responders?

    1. Provided you are NAB negative I don't think treatment changes to another IFN-beta make much of a difference. All the IFN-beta products punt in the same zone of efficacy. If you are a responder to one IFN-beta product you are likely to be a responder to other IFN-beta products. I call this a class effect. If on the other hand you are failing IFN-beta and are switched onto another drug the data suggests you will respond to these drugs, in particular the more effective drugs such as natalizumab and fingolimod.


  2. whether this is really so bad news for msers?
    Now I have a few questions :

    if someone has MS would u give him infb and why ? if u would not why not ?,
    can infb trigger relapse ?

    whether it makes sense to take infb anyway if the outcome all the same ?

    very short and now if someone was diagnosed with MS, which treatment would you recommend and why ?

    thnx for response ..

    but this article is not so optimistic for now

    1. I suggest you watch this video:

  3. very good video, but I'm afraid you've missed the point, if the average flow distability up to 15 years without treatment, how would your opinion be possible delays distability with currently available drugs.

    whether infb really reduced disability in some person or persons have a more peaceful disease course
    Is it possible that some of the medications like infb encourage new relapse
    i wanna to ask u what is it worthwhile to take the medication with all the side effects, if led to the same result as if we didnt take any

    1. The problem is that in the past we did not have more active treatment to escalate MSers if the failed 1st-line injectables. Things have change now. Although the average response to IFN-beta and GA is not very good there are some who do very well; the so called responders. At present we don't have very good predictive markers of who is going to respond and who isn't. We therefore have to offer you a choice of one these treatments and then see how you do. If you remain disease activity free (no relapses, no progression and MRI activity) we classify you as a responder. If you are not DAF then we would switch you to a class of treatment you have not had before or escalate you to one of the more active treatment. This so called active or treat-to-target strategy did not exist 5 or even 10 years ago therefore all the data from this era is not that good or reliable. So in short yes if you think the treatment is worthwhile to go onto a treatment with the aim of seeing if you are responder or not. If not you need to switch treatments. The benefits of DMTs are incremental; with time the increments add up an hopefully this will translate into disability-free world.

  4. Well thxh do much 4 the anwser now it is more clear to me what means mixing tomatoes and apples in reaserch

  5. Disease activity on IFNB is more strongly associated with poor longterm outcomes than disease activity without IFNB:
    could IFNB itself be responsiblr for this? Meaning, is it possible that non-reponders would have been better off if they never took IFNB?


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