Multiple Sclerosis Trial of Avonex and Methotrexate/Methylprednisolone
Avonex (interferon beta 1a) is approved for relapse remitting multiple sclerosis based on studies demonstrating reduction in relapse rates and improvement in EDSS scores. A recent clinical trial sought to determine whether Avonex would work better with the steroid methylprednisolone and the chemotherapeutic agent methotrexate (Cohen et al. Results of the AvonexCombination Trial (ACT) in relapsing-remitting MS. Neurology 2009 Feb 10;72(6):535-41).
The study comprised of 313 patients with relapse remitting multiple sclerosis having an EDSS score between 0-5.5 and one or more relapses or gadolinium-enhancing lesions on MRI while taking Avonex alone in the past year.
Patients were randomized to receive either Avonex alone with placebo, or Avonex with methotrexate, or Avonex with methotrexate and methylprednisolone.
The main goal of the study was to assess whether the intervention would affect the rate of new or bigger lesions at the one year timepoint after treatment as compared to before trial initiation.
Adverse effects of the combinations were not substantially amplified, however no statistically significant improvements or patient benefits were reported using the trial assessment parameters. Interestingly, the patients recieving steroids had a reduced number of antibodies to the Avonex (most likely due to non-specific immune suppression).
In conclusion, this trial did not demonstrate any reason for combining non-specific immune modulators in terms of enhancing efficacy against multiple sclerosis.
It will be interesting to see trials in which immune modulators such as Avonex, which are known at least in part to influence T regulatory cells, are combined with regenerative approaches such as administration of mesenchymal stem cells.