Monday, 21 November 2011

Interferon-beta for PPMS

Tur et al. Interferon Beta-1b for the Treatment of Primary Progressive Multiple Sclerosis: Five-Year Clinical Trial Follow-up. Arch Neurol. 2011 Nov;68(11):1421-7.

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.



MAIN OUTCOME MEASURES: After 5 years without treatment, the EDSS and MSFC measures were scored for 63 and 59 patients, respectively. Neuropsychological and magnetic resonance imaging assessments were performed for 59 and 50 patients, respectively.

EDSS = expanded disability status scale
MSFC = MS functional composite (3 tests are the PASAT, 9-hole peg test and the timed 25-ft walk)
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.

"This is good and bad news for MS'ers with PPMS. It suggest that we have missed a trick and been approaching PPMS trials incorrectly. If this study had been continued for longer than 2 years and extended to 5 years maybe there would have been a clear difference between interferon-beta and placebo. This trial suggests that PPMS may respond to interferon-beta; it is a pity that these results come so late in the life-cycle of the interferon preparations; Pharma is unlikely to spend the necessary resource on a 5-year study."

4 comments:

  1. Were the MSFC tests done at baseline and after the end of the 2-year trial also?
    What were the results of each group (inter1b & placebo) at baseline, 2-years and 5-years post trial?

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  2. First point yes baseline to 5 year and trial termination to 5 year.
    but details vary from different parameters

    Second point. Results varied for each endpoint and the differences on some endpoints did not seem to differ between placebo and treatment for some outcomes.
    As the authors state the influences are small. You my need to read whole paper if really interested. But as G says it is unlikely that definative studies would be done now.

    However, it is clear that some PP MSers (especially the gadolium enhancing people) do gain some benefit from immunosuprression.

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  3. Can 7-year trials ever be feasible? especially with a placebo group?

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  4. Re: "Can 7-year trials ever be feasible? especially with a placebo group?"

    Yes, at the moment we don't have a treatment for PPMS so being a trial is better than being on nothing and watch time go by. I would recommend an adaptive design that allows one to adjust the trial as time goes by. The Fingolimod and Ocrelizumab studies are 3 year placebo controlled trials.

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