Statins類藥物在多發性硬化症方面有時已經佔據頭條，但是許多人推測這個熱潮在「Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome at Risk for Multiple Sclerosis (STAYCIS)」這項研究發表有害於atorvastatin的資料之後會衰退。
October 14, 2009 (Baltimore, Maryland) — Simvastatin, the popular lipid-lowering drug first marketed by Merck as Zocor, is now being investigated in multiple sclerosis. Presenting here at the 134th annual meeting of the American Neurological Association, researchers showed that the drug may target cells involved in the autoimmune response in multiple sclerosis.
"Simvastatin inhibits Th17 cell differentiation in patients with relapsing-remitting multiple sclerosis," lead investigator Xin Zhang, MD, from the University of North Carolina at Chapel Hill, said during an interview. Th17 cells are thought to play a critical role in disease development.
Dr. Zhang's team conducted signaling experiments suggesting that pretreatment with simvastatin altered CD45RA+ cells undergoing Th17 differentiation and inhibited the interferon regulatory factor. The researchers suggest that inhibition is taking place by geranylgeranylation in the dendritic cells.
Dr. Zhang told Medscape Neurology that her colleagues are talking to drug makers about the possibility for new statin trials.
Statins have been making headlines for some time in multiple sclerosis, but many speculated that enthusiasm would wane after Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome at Risk for Multiple Sclerosis (STAYCIS) study investigators presented damaging atorvastatin data.
Presenting at the recent European Committee for Treatment and Research in Multiple Sclerosis annual meeting, researchers described a trial crippled by slow enrollment and recruitment problems.
The Problem with STAYCIS
The 18-month study was a randomized, double-blind, placebo-controlled trial. It explored the effect of 80 mg atorvastatin (Lipitor, Pfizer) in delaying or decreasing clinical and magnetic resonance imaging disease activity.
Investigators focused on patients with clinically isolated syndrome and magnetic resonance findings suggestive of multiple sclerosis. The trial design called for 152 patients, but only 82 were recruited.
"We were underpowered to detect the planned effect," senior investigator Scott Zamvil, MD, from the University of California–San Francisco, told Medscape Neurology at the September meeting. "We had a lack of enrollment, and in hindsight, it was highly unlikely that we were ever going to make our primary endpoint with this design," Dr. Zamvil said. "A phase 2 study like this probably should have had a separate magnetic resonance imaging endpoint."
This is very tragic.
Investigators had hoped that treatment with atorvastatin, known for having a good safety track record, would result in immunologic tolerance. However, the trial was unsuccessful, which means that despite the work of investigators from the 14 centers involved and the efforts of the 82 patients recruited, the study question has no answer.
"This is very tragic," said session cochair Gavin Giovannoni, PhD, from the Institute of Cell and Molecular Science at Barts and the London School of Medicine and Dentistry, in the United Kingdom. "This is an ethical issue and really highlights how important it is to consider logistics and think things through," Dr. Giovannoni said.
During an interview, Henry McFarland, MD, acting chief of the cellular immunology section of the National Institutes of Health, said he agrees, "If you start a study, you have an ethical obligation to see it through and do everything possible to ensure there is a sufficient cohort."
The researchers have disclosed no relevant financial relationships.
American Neurological Association 134th Annual Meeting: Poster T22. Presented October 13, 2009.
