Thursday, 7 February 2013

Predictors of outcome on interferon-beta treatment

#MSBlog Are being treated to make sure you have no evidence of disease activity? How long have you been a NEDA?

Bermel et al. Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta.Ann Neurol. 2013 Jan;73(1):95-103. doi: 10.1002/ana.23758

OBJECTIVE: To identify early predictors of long-term outcomes in MSers with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFNβ-1a).

METHODS: A multicenter, observational, 15-year follow-up study of MSers who completed ≥2 years in the pivotal trial of IM IFNβ-1a for RRMS was conducted. One hundred thirty-six 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 gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 magnetic resonance imaging (MRI); ≥3 new T2 lesions on year 2 MRI compared to baseline; and ≥2 relapses over 2 years. Odds ratios were calculated for early disease activity predicting severe Expanded Disability Status Scale (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: gadolinium-enhancing lesions (odds ratio [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-treated 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.

MS disease activity is like an iceberg; most of the activity you can't see clinically until it is too late and you enter the progressive phase of the disease. Inflammation is not a good thing, which is why we treat-to-target.

"The results of this study are consistent with several data sets that are already published; disease activity on a DMT, in this case interferon-beta, is not good for you. Hence the need for regular MRIs to monitor your disease activity."

"The cynics will quote the Sylvia Lawry Centre and Prof. Ebers and say that relapses and MRI activity don't correlate with anything therefore they should not be used as a treatment target or to predict the course of the disease. Incorrect! The Sylvia Lawry studies were done on the placebo arms of clinical trials, all these MSers were not on any active treatment. However, relapses and MRI activity on DMTs mean something completely different and are telling us something about the biology of MS."

"This is why I have adopted the treat-to-target paradigm the target being NEDA (no evidence of disease activity)."

Other posts of interest

08 Jan 2013
Treat-2-Target: NEDA (no evidence of disease activity). "I would appreciate your comments on the following beta version of a treatment or monitoring algorithm for relapsing MSers. The idea is to adopt the strategy of ...

CoI: multiple


  1. Yessss!! Thank you Prof G.
    Now can someone get your views out to the media as that stupid article in the Independent about 'The MS drugs don't work and the NHS is paying for them' is still hanging around.
    Ebers is wrong! Brilliant news. Although, as someone who has been on Rebif for 12 years and done very well on it, I know that relapses are bad news. It's 2+2 logic - relapses=lesions=illness (albeit temporary with RRMS) = disability.
    I take a DMD - it controls my relapse rate and I'm still walking - although when I've been ill, I haven't been able to walk more than 10 metres. Thanks again Prof G.

  2. Prof G:

    How regular do you recommend MRIs? Annually? And what MRI sequences do you think are useful for monitoring disease activity? The standard T1 and T2-weighted that show white matter lesions?

  3. Gd-enhanced T1 lesions and new T2 lesions. Brain atrophy and oher measure are not ready for prime time yet.


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