Blocking relapses is a good thing

Relapses count. Who disagrees? #MSBlog #MSResearch

"The following study shows that there is a link between relapses and disease progression in clinical trials. Natural history data showing that relapses don't predict disability are not relevant in the current era when most active (relapsing) MSers are on treatment. It is clear that relapses on treatment mean something completely different to relapses on no treatment. Relapse on treatment if it is a maintenance treatment mean you are a non-responder to that treatment, or a sub-optimal responder. If you are on an induction therapy it typically means you need to be retreated. The same applies to focal MRI lesions that are the equivalent of relapses. We all know that poor recovery from relapses is one of the mechanisms that results in disease progression. Therefore the current treatment aim of rendering MSers free of relapses and MRI activity is to try an eliminate this mechanism of disease progression. This strategy however, does not necessarily work for the slow burn that underlies non-relapsing secondary or primary progression."



Epub: Fahrbach et al. Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis. BMC Neurol. 2013 Nov 19;13(1):180. [Epub ahead of print]

BACKGROUND: In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endpoint for most randomized clinical trials (RCTs) is a reduction in relapse rate. It is widely assumed that reducing relapse rate will slow disability progression. Similarly, MRI studies suggest that reducing T2 lesions will be associated with slowing long-term disability in MS. 

OBJECTIVE: The objective of this study was to evaluate the relationship between treatment effects on relapse rates and active T2 lesions to differences in disease progression (as measured by the Expanded Disability Status Scale [EDSS]) in trials evaluating patients with clinically isolated syndrome (CIS), RRMS, and secondary progressive MS (SPMS).

METHODS: A systematic literature review was conducted in Medline, Embase, CENTRAL, and PsycINFO to identify randomized trials published in English from January 1, 1993-June 3, 2013 evaluating DMTs in adult MS patients using keywords for CIS, RRMS, and SPMS combined with keywords for relapse and recurrence. Eligible studies were required to report outcomes of relapse and T2 lesion changes or disease progression in CIS, RRMS, or SPMS patients receiving DMTs and have a follow-up duration of at least 22 months. Ultimately, 40 studies satisfied these criteria for inclusion. Regression analyses were conducted on RCTs to relate differences between the effect of treatments on relapse rates and on active T2 lesions to differences between the effects of treatments on disease progression (as measured by EDSS).

RESULTS: Regression analysis determined there is a substantive clinically and statistically significant association between concurrent treatment effects in relapse rate and EDSS; p < 0.01. Lower treatment effects were associated with higher relative rates of disease progression. Significant associations between T2 lesion measures and EDSS measures also were found (p < 0.05), with some suggestion that the strength of the association may differ for older versus newer DMTs.

CONCLUSIONS: Treatment differences in relapse reduction and T2 lesions are positively related to differences in disease progression over the first two years of treatment.

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