Allison Gandey

October 22, 2010

October 22, 2010 (Gothenburg, Sweden) — A large phase 2 study has returned disappointing results for statin therapy in multiple sclerosis (MS). Investigators report simvastatin was less effective than placebo on all primary and secondary endpoints.

"The study gave a clear result that simvastatin cannot be recommended as an add-on therapy to intramuscular interferon beta-1a," said Per Soelberg Sorensen, MD, from Copenhagen University Hospital in Denmark.

Simvastatin was less effective than placebo.

The results were presented here at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis.

One recent study showed that combination atorvastatin and interferon increased magnetic resonance imaging (MRI) and clinical disease activity. Another study demonstrated a beneficial effect of the combination. Investigators say it is still too early to tell whether this finding corroborates the feared deleterious effect of statins on interferon in immunomodulation, but the concern is valid.

In this multicenter, double blind, randomized controlled trial, investigators enrolled 307 treatment-naive patients with relapsing-remitting MS. The study used a parallel group design, and patients received therapy for up to 3 years.

Patients were prescribed intramuscular interferon beta-a 30 μg weekly and then were randomly assigned to receive placebo or simvastatin 40 mg per day for the first month, then 80 mg per day. Investigators performed brain MRI at baseline and at 1 year. Clinical follow-up took place every 3 months.

The primary outcome for the trial was the annual rate of documented relapses. In the intention-to-treat analysis, the annual relapse rate was similar between the simvastatin and placebo groups. The mean number of new or enlarging T2 lesions on MRI was higher in the simvastatin group, and more patients were disease-activity-free in the placebo group compared with simvastatin.

The time to first documented relapse was 653 days for patients receiving placebo and 551 days for those receiving simvastatin. Dr. Sorensen reported other exploratory endpoints, including 3 months of sustained increases in Expanded Disability Status Scale. A total of 37 patients receiving placebo and 43 patients receiving simvastatin experienced a 1-point increase on the scale. Change in brain parenchymal fraction was −0.8% for placebo and −1.0% for simvastatin.

The investigators report no unexpected adverse events.

Session chair Carlo Pozzilli, MD, from La Sapienza University in Rome, Italy, said the negative result is valuable. Although there was no benefit in MS, he noted, the study does establish the drug's safety. He pointed out the simvastatin dose was higher than what is usually prescribed, and still, the combination was not dangerous.

Comparing Atorvastatin

During the question period after the presentation, an attendee asked whether this study represents the final nail in the statins-for-MS coffin. "No further studies are needed," Dr. Sorensen replied.

However, not everyone agrees. Emmanuelle Waubant, MD, lead investigator of the Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome at Risk for Multiple Sclerosis (STAYCIS) study, told Medscape Medical News at the recent American Neurological Association annual meeting that imaging data suggest statins may play a role in reducing new brain lesions.

STAYCIS was the highly anticipated statin trial that failed. Attempts to evaluate atorvastatin in patients with clinically isolated syndrome were crippled by slow enrolment and recruitment problems, and the trial ended without an answer to the study question. The trial has been criticized for its lack of power.

The 18-month trial proved to be a tough sell for patients who were scheduled to receive atorvastatin or placebo for 12 months, and then no treatment for the remaining 6 months of the study.

Despite the challenges, Dr. Waubant says she has not observed any deleterious effect of combination therapy with interferon and atorvastatin. "Additional studies are warranted," she said.

New Studies

Jeffrey Cohen, MD, from the Cleveland Clinic Foundation in Ohio, points out that although he is not certain of the clinical utility of these drugs for MS, he would like more data on the safety of the combination. During a session at the end of the meeting, he reviewed the new findings as part of the meeting highlights.

"These results do not support the utility of combining at least this particular statin with this particular interferon," Dr. Cohen said. "There are several other studies that had somewhat different results, but overall, I think this suggests this is probably not a useful combination in MS."

However, he added, "I think the more difficult issue is what to do about our patients with MS on interferon who are being treated for hyperlipidemia with statins, and we're going to need further data on that question."

The presenters have disclosed no relevant financial relationships.

26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Presented October 16, 2010.

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