ARTICLE IN BRIEF
Investigators concluded that reducing the costs of certain MS medication by two-thirds would make them nearly cost-effective.
A study of injectable medications for multiple sclerosis (MS) found them modestly effective at slowing disease progression and reducing relapses, but nevertheless questioned their cost-effectiveness due to their high cost in the US.
“As a society we‘re investing a lot to produce small-to-moderate gains, and we didn‘t even study natalizumab and other costly treatments,” said Robert G. Holloway, MD, MPH, one of the authors of the study (funded in part by the National Multiple Sclerosis Society) and a professor of neurology and community and preventive medicine at the University of Rochester in New York. “Since such a large part of the cost of caring for MS patients goes for medications, reducing their cost could make an impact on the cost-effectiveness of the therapy.”
The study, which appeared online July 20 before the print edition of Neurology, determined the cost-effectiveness of intramuscular forms of beta-1a, as well as glatiramer acetate, by examining data accumulated from 2000-2005 on 910 MS patients participating in the Sonya Slifka Longitudinal Multiple Sclerosis study. The cohort constituted a representative sample of the MS population in the US in terms of the duration and severity of their disease, and the extent of their disability.
Using 10-year disease progression estimates, the authors measured the outcomes of these disease-modifying therapies in terms of quality-adjusted life years (QALYs), and relapse-free years. All the medications produced modest health gains, but at a cost exceeding $800,000 per QALY. Reducing the costs of medication by two-thirds, which would approximate prices paid in the UK and other countries, would make the MS treatments studied nearly cost-effective, the authors concluded. Also, starting treatment earlier produced a better cost-effectiveness ratio, they found.
QUESTIONS ABOUT METHODOLOGY
Other neurologists questioned the methodology of the study, which used a relatively small sample size over a relatively short period to model a highly variable chronic disease that progresses over decades.
“A lot of the patients in this study — both the relapsing-remitting and the secondary-progressive patients — would have had established disease for some time before the drugs were available, so they don‘t necessarily represent patients who have been treated in the last five to seven years,” said Robert Lisak, MD, Parker Webber Chair and professor of neurology at Wayne State University, and chair of the AAN MS Section. “As a result, the course of their disease might have been different if they had received newer drugs earlier. Also, we are diagnosing MS earlier, so there‘s less burden of disease, and that isn‘t represented in the databases. Using data from the Slifka Survey, which is small, has its own limitations, and modeling the natural history of MS is fraught with danger, so that part of the analysis is potentially quite flawed.”
However, cost-effectiveness studies vary widely, from $2 million per QALY to actual cost savings, according to Dr. Holloway, an associate editor of Neurology Today. Studies funded by the pharmaceutical industry tend to report better cost-effectiveness.
“It should be no surprise given the well-known ‘funding effect,‘ which shows that studies supported by industry are more likely to report more favorable cost-effectiveness for these medications than studies not industry-supported,” he said. “Pharmaceutical companies have become one of the biggest funders of cost-effectiveness research. They use these studies as ‘marketing tools.‘ Our study is an example of a non-industry-supported effort showing estimates of cost-effectiveness on the high side — so high that by some standards, usually less than $100,000 to $200,000 per QALY, they are not considered good investments in health.”
Bruce A. Cohen, MD, professor of neurology and director of the Comprehensive Multiple Sclerosis Program at Northwestern University‘s Feinberg School of Medicine, who was not involved with the analysis, agreed that the decade-long model of the disease used in the study might be inadequate.
“Ten years is not a long time in MS,” he said. “This is a disease that often spans 25-30 years. Also, the investigators point out that the database has a limited number of people with advanced disease, which is important because there‘s a body of literature not restricted to pharmaceutical studies that demonstrates the increased cost of MS in relation to increased severity. If early treatment delays the onset of progressive disease, the savings may be seen over a longer interval.”
Moreover, he added, the high cost of the drugs is hard to pin down. “For example, the study estimates a cost of $68,000 per year for an individual who is wheelchair-bound, which is likely more than double what third-party payers actually pay for these drugs. The stated cost of these drugs represents a retail cost that few insurance companies pay. The actual cost to third-party payers, which is considered proprietary information, is substantially less. Insurance companies negotiate with pharmaceutical companies, and use a rebate system based on volume so the net cost of the drug is less than the list price, which obviously would affect the cost-effectiveness ratios they‘re calculating. However, that net cost information is not available to them.”
COST-ESTIMATES ARE CONSERVATIVE
John Corboy, MD, professor of neurology at the University of Colorado-Denver, recently gathered information on the cost of MS medications for a talk on “the discontinuation of disease-modifying therapies in MS,” and he considers the costs used in the paper to be conservative.
“They‘re taken from 2008, and the numbers have gone up over 60 percent since then,” he said. “It‘s clear the cost of these medications in the US is astounding. Gilenya [fingolimod] came on market in September of 2010. It costs $52,000 per year. On Jan. 6, 2011, the Wholesale Acquisition Cost of Copaxone (glatiramer acetate) went from $34,000 to $41,000 per year. Why? Because no one told the manufacturer not to raise it. It‘s like reverse capitalism. Greater competition usually means prices go down, but it‘s the opposite with drugs. This market doesn‘t make any sense.”
[An article published earlier this year in Neurology Today found that the high-cost of MS drugs were contributing to problems with compliance: http://bit.ly/naU33k]
One big reason for the high prices in this country, he said, is the Medicare drug plan enacted under President George W. Bush, which prohibits the US government from negotiating with pharmaceutical companies over the cost of drugs, as other countries do. Meanwhile, the Department of Veterans Affairs and other agencies are allowed to negotiate paying drastically less for the same drugs — for example, $14,000 for glatiramer acetate instead of $41,000, according to Dr. Corboy. Prices in Canada and throughout Europe also are dramatically lower.
“Even at the lower costs these are astoundingly expensive drugs,” he said, “and this study does not take into account two new medications: natalizumab (Tysabri) and fingolimod.”
THE TOP 5 LIST FOR ‘LITTLE BENEFIT‘
Last year, in a controversial article in the New England Journal of Medicine, Howard Brody, MD, PhD, challenged physicians in all specialties to draw up a “top 5 list” of common diagnostic tests or treatments that have been shown to provide little meaningful benefit. Despite the lack of evidence for cost-effectiveness of MS medications found by the authors of the Neurology study, he does not believe those drugs belong on the top 5 list for neurology.
“A treatment that provides some benefit even at high cost is almost by definition not eligible for the top 5 list,” said Dr. Brody, John P. McGovern Centennial Chair in Family Medicine, and director of the Institute for the Medical Humanities at the University of Texas Medical Branch in Galveston. “The goal would be to get rid of stuff that‘s just plain a waste of money because it provides zero benefit. It would be wrong to go after something that has demonstrable benefit.”
Asked for MS treatments that might be candidates for neurology‘s top 5 list, neurologists point to medications given to people who probably won‘t benefit from them.
Dr. Corboy, for example, suggested discontinuing MS medications for people over 50 with longstanding benign MS, who stand to gain little benefit from them. “The medications we use for disease modification in MS show demonstrable benefit, but not for all patients,” he said. “We have many criteria for beginning therapies, but almost no criteria for ending therapies, and I think both doctors and patients share responsibility — doctors because, in an effort to offer hope, we tend to offer drugs to patients rather than tell them we don‘t‘ have an effective therapy, and patients for just wanting us to do something to treat their chronic illness.”
Dr. Cohen suggested withholding certain medications from people with non-relapsing forms of MS. “I believe FDA-approved meds all have a role in treating relapsing forms of MS, but I don‘t believe any have shown benefit in non-relapsing forms,” he said. “One could argue they shouldn‘t be given to an individual who doesn‘t have a relapsing form of MS. They haven‘t shown benefit.”
And while Dr. Brody emphasized that he is not a neurologist, he suggested that an over-reliance on diagnostic MRI scans might belong on neurology‘s top 5 list, especially when done by physicians who have a financial interest in the scanning machinery.
Dr. Cohen took exception to that view. “The fact is we don‘t do as many invasive procedures anymore because of MRI scans,” Dr. Cohen said. “Examples would include myelograms and exploratory surgical procedures. Furthermore, no other test currently available gives you information on the tissue of the CNS like MRI scans and there is no radiation exposure for the patient…. We can now diagnose MS before the evidence of physical disability appears because of MRI, possibly mitigating that disability by instituting earlier treatment. Small tumors not seen on CT can be visualized by MRI. If any imaging test is to be attacked, it would be the indiscriminate use of CT scanning for CNS disease when MRI would be more informative, resulting in people getting both tests when just the MRI might do.”
What did you miss? For an extended discussion about the cost-effectiveness of disease-modifying therapy for MS, tune in to the July 26 podcast interview on neurology.org with study author Katia Noyes, MPH, PhD, associate professor of community and preventive medicine at the University of Rochester. Mark Keegan, MD, associate professor of neurology at Mayo Clinic in Rochester, MN, is the interviewer.