SIMCOMBIN dashes statin hopes for MS patients
MedWire News: Adding simvastatin to interferon beta does not improve outcomes of patients with relapsing-remitting multiple sclerosis (MS), show results of a randomized trial.
The SIMCOMBIN study, which appears in The Lancet Neurology, is the largest to date that has tested interferon beta in combination with a statin in patients with MS. The various clinical trials were designed to build on the finding that statins induce T-cell-mediated immune modulation and reverse paralysis in mice with experimental autoimmune encephalomyelitis.
Despite the negative findings of SIMCOMBIN, Per Sorensen (Rigshospitalet, Copenhagen, Denmark) and colleagues note that combinations of "other statins with other disease-modifying drugs such as glatiramer acetate could still be beneficial for treatment of this disease."
The SIMCOMBIN investigators randomly assigned 307 patients with relapsing-remitting MS to receive treatment with intramuscular interferon beta (30 µg/week) plus either high-dose simvastatin (80 mg/day) or placebo.
During an average follow-up of about 21 months, patients in the combination treatment group had an average of 0.19 documented relapses per year, and those in the monotherapy group had an average of 0.14 per year.
Documented relapses were those causing at least a 1-point increase in symptoms for two functional systems or at least 2 points for one system, or at least half a point on the Kurtzke expanded disability status scale.
The absolute difference between the two groups, of 0.059 relapses per year, was not statistically significant.
The annual rates of all reported relapses, regardless of whether they met the criteria for a documented relapse, were 0.44 and 0.38 in the combination therapy and monotherapy groups, respectively. Again, the difference was not significant.
There were also no significant differences between the two groups in time to first documented relapse, or in the percentage of patients who had progression lasting at least 3 months, or remained relapse-free throughout the trial. The two groups had similar numbers of new or enlarging lesions on imaging after 12 months of treatment.
But, on the whole, all outcomes were slightly better in patients who took interferon beta alone than in those given combination therapy.
In a related commentary, Scott Zamvil (University of California, San Francisco, USA) and Lawrence Steinman (Stanford University, California) noted that the hint of an antagonistic effect of combination therapy could be caused by the two drugs having opposing effects on STAT (signal transducers and activators of transcription)1.
"As predictive medicine becomes a standard for choice of drugs, examination of potential synergies will be worthwhile, to see whether inexpensive drugs approved for other conditions can improve efficacy of drugs for multiple sclerosis in responder populations," they said.
But they cautioned: "One ought to be careful when combining treatments in multiple sclerosis. In view of the lack of benefit and the potential for antagonism, one might want to think twice before adding a statin to interferon beta in multiple sclerosis treatment."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Eleanor McDermid