“This is a reposting; I originally discussed this publication 21 November 2011. The interpretation of this paper has become more important after comments in relation to a post yesterday on the ‘10 year course of MS‘.”
“What this study shows is that when a cohort of PPMSers who were in a trial of interferon were followed up 5 years later it was clear that PPMSer who had been treated with IFNbeta for 2-years had clearly done better than PPMSers on placebo. This means that the impact of anti-inflammatory medications in progressive MS may take several years to play out. In other words progression over the next 2 years was primed by inflammation two years ago; this is why the study was negative. Therefore suppressing inflammation today will have not impact of 2-3 years as this damage has already occurred. In other words we need to take into account a lag from treatment to response. If this is the case we have yet to learn the lesson almost all SPMS and PPMS trials are running for 2-3 years without a lag phase analysis built into the design of the study. Why has this occurred? I am not sure; one reason is that it is very expensive to do 5 year trials. I remain convinced that inflammation plays a role in progressive MS and that we need to suppress it in addition to using neuroprotective agents to try and prevent loss of those axons and neurons that are destined to die from previous inflammation.”
“Is the lag concept as presented here understandable to you? I have drawn a hypothetical picture to model this delayed effect.”
OBJECTIVES: To investigate, during the 5-year period without treatment after termination of a 2-year clinical trial of interferon beta-1b for the treatment of PPMS.
9-Hole Peg Test = test of upper limb function
Word List Generation Test = cognitive task
RESULTS: After 5 years without treatment, the interferon beta-1b group had better 9-Hole Peg Test (p=0.02) and Word List Generation Test (p<0.001) scores, and MRI measures in the normal-appearing white matter were significantly better. During the entire study period (from trial baseline to assessment at 5 years without treatment), the placebo group showed a greater decrease in brain volume (p=0.004). The in-trial increase of lesions correlated with the worsening of the EDSS score during the 5-year period without treatment (p =0.004).
CONCLUSIONS: Modest but beneficial effects of interferon beta-1b on clinical variables and brain atrophy development were observed 5 years after trial termination. Moreover, in-trial lesion activity correlated with EDSS progression after trial termination. Therefore, we provide evidence to consider immunomodulation as a sensible approach to treat primary progressive multiple sclerosis.