Predicting a failure to interferon-beta treatment

Are you failing on your DMT? if you are not sure this post is for you. #MSBlog #MSResearch

“You may have heard me banging on endlessly about treating-2-target of NEDA (no evidence of disease activity) and my ZeTo  or zero tolerance strategy of not tolerating disease activity, either clinically or on MRI. The study below supports this strategy in that MSers on IFNbeta who have either clinical or subclinical (MRI only) evidence of disease activity do much worse in terms of disability worsening.”

“Some of you will start jumping up and down and hitting the comment button quoting Professor George Ebers, who claims that outside the first 2 years relapses don’t count. I disagree. Professor Ebers’ data is based on natural history studies and not in MSers on treatment. Why the difference? I don’t know, but I suspect that relapses are in response to what is causing MS in the nervous system and whether or not you have relapses, or not, makes little difference to the long-term prognosis off treatment as the underlying MS disease process goes on unchecked. However, if you are on a treatment that targets the underlying MS disease process, for example it may switch off or suppress a virus, then the relapses will stop as the stimulus for triggering the relapses is suppressed. However, if your treatment does not work and the MS disease process continues unabated then you will continue to have relapses, and/or MRI activity. Therefore in treated MSers relapses and/or MRI activity mean something completely different to that occurring in MSers not on treatment. Does this explanation make any sense?” 

“In addition to the long-term outcomes relapses also cause problems for individual MSers. Firstly, they are a reminder that you that you have MS, which may exacerbate anxiety. Secondly, some are disabling and may cause you to miss work, or your studies. Thirdly, steroid treatment for relapses may be associated with side effects, which in some cases can be very serious, for example avascular necrosis of the hip. Fourthly, you don’t necessarily make a full recovery from relapses, which may increase your disability. Finally, relapses cost money; the economic costs of loss of work and consumption of healthcare resources should not be overlooked. In conclusion, if you have relapsing MS it is better to be relapse-free that to continue having relapses. It still surprises me that some therapeutic nihilists disease agree with me on this issue.”

“In the past I have spoken about the MS Treatment doughnut, which this study illustrates very well. If you are failing DMTs on MRI criteria only, and not clinically, you will not fulfill contemporary criteria to have your treatment escalated. In other words the EMA, and NICE in the UK, do not accept MRI activity as an indication that you are failing treatment. This is why I campaigning to reclassify MRI activity as subclinical relapses. If we start referring to the development of new lesions as relapses, healthcare payers may start to accept MRI activity (new or enlarging T2 lesions and Gad-enhancing lesions) as a surrogate for relapses.”

Epub: Prosperini et al. Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis. Mult Scler. 2013 Sep.

OBJECTIVE: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated MSers according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment.

METHODS: A total of 370 MSers with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in MSers fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity.

RESULTS: A total of 192 (51.9%) MSers relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either MSers fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable MSers (all p values <0.001).

CONCLUSION: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • Prof G,

    Many thanks for this. I've had excellent results from Campath – NEDA. I think it may be working by interfering with the underlying disease process ie EBV infection.

    Best wishes with the Charcot project.

By Prof G



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