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Medical marijuana: Tips from an expert
ORLANDO – An essential element in prescribing medical marijuana responsibly is to insist that the patient must demonstrate improved functional status to be allowed to continue with the therapy, one expert has advised.
"Functional status is really the major issue. If cannabis is going to be used as a medicine, we have to see improvement in function: return to work, improvement in daily activities, engagement in society. I tell patients, ‘If this drug is really helping you, then show me. Show me that you can come off this other medication or reduce the dose. Show me you can go out and do volunteer work or join a club. Prove to me that this is valuable to you, because I cannot continue to authorize access to a substance if you cannot show me that it’s actually helping you improve your quality of life.’ That’s the gauntlet I throw down to patients," Dr. Mark A. Ware said at the fifth Cooperative Meeting sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Through this requirement, a physician can validate that a patient with chronic non-cancer pain, epilepsy, HIV, multiple sclerosis, or any of the various other conditions for which medical marijuana is often used is not merely using the prescription recreationally, sitting around the house in a fog watching "M*A*S*H" reruns on television all day, explained Dr. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit at McGill University in Montreal.
Canada has had a federal program for medical marijuana in place for a dozen years. Dr. Ware has extensive experience in prescribing medical marijuana in the pain clinic, where many patients report improvement not only in pain, but in spasticity, sleep, and/or mood. In addition, he has led randomized clinical trials that demonstrated that smoked cannabis reduced pain intensity and improved sleep quality in patients with chronic neuropathic pain (CMAJ 2010;182:E694-701) and that oral nabilone (Cesamet), a synthetic cannabinoid, improved sleep and was well tolerated in patients with fibromyalgia (Anesth. Analg. 2010;110:604-10).
He offered these tips for physicians who have patients asking about medical marijuana:
The doses used are modest: A World Health Organization report estimated that the average joint contains 0.5 g of cannabis, and that the average dose in patients using marijuana medically is four joints per day, or roughly 2 g of cannabis. That equates to 20-50 mg/day of tetrahydrocannabinol, the active molecule, which is consistent with the results of clinical trials using standardized extracts.
"A watchful dose is 5 g of cannabis per day. I would be very, very cautious about anybody who’s asking for more than 5 g/day. The likelihood of diversion goes way up. There’s very little reason on pharmacologic grounds why a patient would need that much," Dr. Ware advised.
Not everyone responds to medical marijuana: As with any other medication, there are nonresponders. Because cannabis has been widely available recreationally for so long, an individual’s past recreational experience can be used as a rough predictor of the likelihood of response to medical marijuana.
"One of the tests I use when a patient with a chronic medical illness comes in asking if maybe a cannabis-based drug could be useful is I ask if they’ve ever used the drug before, say, in college or high school. If they say they did and got anxious and paranoid and hated it, that tells me they’re not cannabinoid responders. I have no scientific evidence for this, it’s just a clinical tool I use. Prior positive recreational responders, I suspect, are more likely to have a favorable effect," Dr. Ware continued.
Most patients are more concerned about medical marijuana’s safety than effectiveness: Medical cannabinoids are "overall quite safe," according to the family physician, who with coauthors has published a systemic review of the adverse effects (CMAJ 2008;178:1669-78). Cannabis has no associated toxicity even at extremely high doses. The prescription oral cannabinoids have no apparent abuse potential. While dependence is seen in some recreational marijuana smokers, it doesn’t seem to occur with clinical use.
And regarding the key safety concern for most patients and physicians – the question of smoked marijuana’s effects on the lung (see accompanying story) – a new analysis of the published literature by one of the world’s pre-eminent pulmonologists, Dr. Donald P. Tashkin, emeritus professor of medicine and medical director of the pulmonary function laboratory of the University of California, Los Angeles, concluded that "the accumulated weight of evidence" suggests regular smoking of marijuana alone doesn’t increase the risk of lung or upper airway cancer or [chronic obstructive pulmonary disease] , and the evidence is inconclusive regarding a possible associated risk of lower respiratory tract infection (Ann. Am. Thorac. Soc. 2013;10:239-47).
Medical marijuana is contraindicated in adolescents and patients with unstable ischemic heart disease or a personal or family history of psychosis: All of the clinical trials have screened for and excluded patients with a history of psychosis, either personally or in a first-degree relative. So there is no evidence supporting its safe use in such individuals.
A growing number of case reports suggest recreational cannabis use in young adolescents can trigger a latent psychotic episode in selected susceptible individuals. This is a major concern.
Cannabis is a powerful peripheral vasodilator. "The way to remember that is the red eyes of Bob Marley," Dr. Ware suggested. Peripheral vasodilation results in an increased heart rate, which could trigger an MI in a patient with unstable ischemic heart disease.
Always ask about legal issues: A surprisingly large number of patients inquiring about medical marijuana are under investigation for a crime and are seeking a stay-out-of-jail card. They won’t mention it if they’re not asked.
Consider the prescription alternatives to medical pot: Nabilone and Marinol (dronabinol, which is tetrahydrocannabinol), are approved for prescription use in the United States. The beneficial effects last longer than with smoked cannabis, and there is no uncertainty about the concentration, source, or possible contaminants.
Keep an eye out for improved technology: Smoking is a dirty delivery system for marijuana. While it’s not nearly as harmful to the lungs as smoking tobacco, as Dr. Tashkin recently concluded, cannabis smoke nevertheless does contain carcinogens and toxins. Vaporization devices are now commercially available as an alternative: a smokeless marijuana delivery system. This approach has recently been shown effective in a randomized, double-blind, placebo-controlled, crossover clinical trial conducted in patients with neuropathic pain (J. Pain 2013;14:136-48).
Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.
ORLANDO – An essential element in prescribing medical marijuana responsibly is to insist that the patient must demonstrate improved functional status to be allowed to continue with the therapy, one expert has advised.
"Functional status is really the major issue. If cannabis is going to be used as a medicine, we have to see improvement in function: return to work, improvement in daily activities, engagement in society. I tell patients, ‘If this drug is really helping you, then show me. Show me that you can come off this other medication or reduce the dose. Show me you can go out and do volunteer work or join a club. Prove to me that this is valuable to you, because I cannot continue to authorize access to a substance if you cannot show me that it’s actually helping you improve your quality of life.’ That’s the gauntlet I throw down to patients," Dr. Mark A. Ware said at the fifth Cooperative Meeting sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Through this requirement, a physician can validate that a patient with chronic non-cancer pain, epilepsy, HIV, multiple sclerosis, or any of the various other conditions for which medical marijuana is often used is not merely using the prescription recreationally, sitting around the house in a fog watching "M*A*S*H" reruns on television all day, explained Dr. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit at McGill University in Montreal.
Canada has had a federal program for medical marijuana in place for a dozen years. Dr. Ware has extensive experience in prescribing medical marijuana in the pain clinic, where many patients report improvement not only in pain, but in spasticity, sleep, and/or mood. In addition, he has led randomized clinical trials that demonstrated that smoked cannabis reduced pain intensity and improved sleep quality in patients with chronic neuropathic pain (CMAJ 2010;182:E694-701) and that oral nabilone (Cesamet), a synthetic cannabinoid, improved sleep and was well tolerated in patients with fibromyalgia (Anesth. Analg. 2010;110:604-10).
He offered these tips for physicians who have patients asking about medical marijuana:
The doses used are modest: A World Health Organization report estimated that the average joint contains 0.5 g of cannabis, and that the average dose in patients using marijuana medically is four joints per day, or roughly 2 g of cannabis. That equates to 20-50 mg/day of tetrahydrocannabinol, the active molecule, which is consistent with the results of clinical trials using standardized extracts.
"A watchful dose is 5 g of cannabis per day. I would be very, very cautious about anybody who’s asking for more than 5 g/day. The likelihood of diversion goes way up. There’s very little reason on pharmacologic grounds why a patient would need that much," Dr. Ware advised.
Not everyone responds to medical marijuana: As with any other medication, there are nonresponders. Because cannabis has been widely available recreationally for so long, an individual’s past recreational experience can be used as a rough predictor of the likelihood of response to medical marijuana.
"One of the tests I use when a patient with a chronic medical illness comes in asking if maybe a cannabis-based drug could be useful is I ask if they’ve ever used the drug before, say, in college or high school. If they say they did and got anxious and paranoid and hated it, that tells me they’re not cannabinoid responders. I have no scientific evidence for this, it’s just a clinical tool I use. Prior positive recreational responders, I suspect, are more likely to have a favorable effect," Dr. Ware continued.
Most patients are more concerned about medical marijuana’s safety than effectiveness: Medical cannabinoids are "overall quite safe," according to the family physician, who with coauthors has published a systemic review of the adverse effects (CMAJ 2008;178:1669-78). Cannabis has no associated toxicity even at extremely high doses. The prescription oral cannabinoids have no apparent abuse potential. While dependence is seen in some recreational marijuana smokers, it doesn’t seem to occur with clinical use.
And regarding the key safety concern for most patients and physicians – the question of smoked marijuana’s effects on the lung (see accompanying story) – a new analysis of the published literature by one of the world’s pre-eminent pulmonologists, Dr. Donald P. Tashkin, emeritus professor of medicine and medical director of the pulmonary function laboratory of the University of California, Los Angeles, concluded that "the accumulated weight of evidence" suggests regular smoking of marijuana alone doesn’t increase the risk of lung or upper airway cancer or [chronic obstructive pulmonary disease] , and the evidence is inconclusive regarding a possible associated risk of lower respiratory tract infection (Ann. Am. Thorac. Soc. 2013;10:239-47).
Medical marijuana is contraindicated in adolescents and patients with unstable ischemic heart disease or a personal or family history of psychosis: All of the clinical trials have screened for and excluded patients with a history of psychosis, either personally or in a first-degree relative. So there is no evidence supporting its safe use in such individuals.
A growing number of case reports suggest recreational cannabis use in young adolescents can trigger a latent psychotic episode in selected susceptible individuals. This is a major concern.
Cannabis is a powerful peripheral vasodilator. "The way to remember that is the red eyes of Bob Marley," Dr. Ware suggested. Peripheral vasodilation results in an increased heart rate, which could trigger an MI in a patient with unstable ischemic heart disease.
Always ask about legal issues: A surprisingly large number of patients inquiring about medical marijuana are under investigation for a crime and are seeking a stay-out-of-jail card. They won’t mention it if they’re not asked.
Consider the prescription alternatives to medical pot: Nabilone and Marinol (dronabinol, which is tetrahydrocannabinol), are approved for prescription use in the United States. The beneficial effects last longer than with smoked cannabis, and there is no uncertainty about the concentration, source, or possible contaminants.
Keep an eye out for improved technology: Smoking is a dirty delivery system for marijuana. While it’s not nearly as harmful to the lungs as smoking tobacco, as Dr. Tashkin recently concluded, cannabis smoke nevertheless does contain carcinogens and toxins. Vaporization devices are now commercially available as an alternative: a smokeless marijuana delivery system. This approach has recently been shown effective in a randomized, double-blind, placebo-controlled, crossover clinical trial conducted in patients with neuropathic pain (J. Pain 2013;14:136-48).
Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.
ORLANDO – An essential element in prescribing medical marijuana responsibly is to insist that the patient must demonstrate improved functional status to be allowed to continue with the therapy, one expert has advised.
"Functional status is really the major issue. If cannabis is going to be used as a medicine, we have to see improvement in function: return to work, improvement in daily activities, engagement in society. I tell patients, ‘If this drug is really helping you, then show me. Show me that you can come off this other medication or reduce the dose. Show me you can go out and do volunteer work or join a club. Prove to me that this is valuable to you, because I cannot continue to authorize access to a substance if you cannot show me that it’s actually helping you improve your quality of life.’ That’s the gauntlet I throw down to patients," Dr. Mark A. Ware said at the fifth Cooperative Meeting sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Through this requirement, a physician can validate that a patient with chronic non-cancer pain, epilepsy, HIV, multiple sclerosis, or any of the various other conditions for which medical marijuana is often used is not merely using the prescription recreationally, sitting around the house in a fog watching "M*A*S*H" reruns on television all day, explained Dr. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit at McGill University in Montreal.
Canada has had a federal program for medical marijuana in place for a dozen years. Dr. Ware has extensive experience in prescribing medical marijuana in the pain clinic, where many patients report improvement not only in pain, but in spasticity, sleep, and/or mood. In addition, he has led randomized clinical trials that demonstrated that smoked cannabis reduced pain intensity and improved sleep quality in patients with chronic neuropathic pain (CMAJ 2010;182:E694-701) and that oral nabilone (Cesamet), a synthetic cannabinoid, improved sleep and was well tolerated in patients with fibromyalgia (Anesth. Analg. 2010;110:604-10).
He offered these tips for physicians who have patients asking about medical marijuana:
The doses used are modest: A World Health Organization report estimated that the average joint contains 0.5 g of cannabis, and that the average dose in patients using marijuana medically is four joints per day, or roughly 2 g of cannabis. That equates to 20-50 mg/day of tetrahydrocannabinol, the active molecule, which is consistent with the results of clinical trials using standardized extracts.
"A watchful dose is 5 g of cannabis per day. I would be very, very cautious about anybody who’s asking for more than 5 g/day. The likelihood of diversion goes way up. There’s very little reason on pharmacologic grounds why a patient would need that much," Dr. Ware advised.
Not everyone responds to medical marijuana: As with any other medication, there are nonresponders. Because cannabis has been widely available recreationally for so long, an individual’s past recreational experience can be used as a rough predictor of the likelihood of response to medical marijuana.
"One of the tests I use when a patient with a chronic medical illness comes in asking if maybe a cannabis-based drug could be useful is I ask if they’ve ever used the drug before, say, in college or high school. If they say they did and got anxious and paranoid and hated it, that tells me they’re not cannabinoid responders. I have no scientific evidence for this, it’s just a clinical tool I use. Prior positive recreational responders, I suspect, are more likely to have a favorable effect," Dr. Ware continued.
Most patients are more concerned about medical marijuana’s safety than effectiveness: Medical cannabinoids are "overall quite safe," according to the family physician, who with coauthors has published a systemic review of the adverse effects (CMAJ 2008;178:1669-78). Cannabis has no associated toxicity even at extremely high doses. The prescription oral cannabinoids have no apparent abuse potential. While dependence is seen in some recreational marijuana smokers, it doesn’t seem to occur with clinical use.
And regarding the key safety concern for most patients and physicians – the question of smoked marijuana’s effects on the lung (see accompanying story) – a new analysis of the published literature by one of the world’s pre-eminent pulmonologists, Dr. Donald P. Tashkin, emeritus professor of medicine and medical director of the pulmonary function laboratory of the University of California, Los Angeles, concluded that "the accumulated weight of evidence" suggests regular smoking of marijuana alone doesn’t increase the risk of lung or upper airway cancer or [chronic obstructive pulmonary disease] , and the evidence is inconclusive regarding a possible associated risk of lower respiratory tract infection (Ann. Am. Thorac. Soc. 2013;10:239-47).
Medical marijuana is contraindicated in adolescents and patients with unstable ischemic heart disease or a personal or family history of psychosis: All of the clinical trials have screened for and excluded patients with a history of psychosis, either personally or in a first-degree relative. So there is no evidence supporting its safe use in such individuals.
A growing number of case reports suggest recreational cannabis use in young adolescents can trigger a latent psychotic episode in selected susceptible individuals. This is a major concern.
Cannabis is a powerful peripheral vasodilator. "The way to remember that is the red eyes of Bob Marley," Dr. Ware suggested. Peripheral vasodilation results in an increased heart rate, which could trigger an MI in a patient with unstable ischemic heart disease.
Always ask about legal issues: A surprisingly large number of patients inquiring about medical marijuana are under investigation for a crime and are seeking a stay-out-of-jail card. They won’t mention it if they’re not asked.
Consider the prescription alternatives to medical pot: Nabilone and Marinol (dronabinol, which is tetrahydrocannabinol), are approved for prescription use in the United States. The beneficial effects last longer than with smoked cannabis, and there is no uncertainty about the concentration, source, or possible contaminants.
Keep an eye out for improved technology: Smoking is a dirty delivery system for marijuana. While it’s not nearly as harmful to the lungs as smoking tobacco, as Dr. Tashkin recently concluded, cannabis smoke nevertheless does contain carcinogens and toxins. Vaporization devices are now commercially available as an alternative: a smokeless marijuana delivery system. This approach has recently been shown effective in a randomized, double-blind, placebo-controlled, crossover clinical trial conducted in patients with neuropathic pain (J. Pain 2013;14:136-48).
Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.
AT THE CMSC/ACTRIMS ANNUAL MEETING
Urinary symptoms often unaddressed in MS
ORLANDO – Lower urinary tract symptoms in patients with multiple sclerosis are common, bothersome, and often undiscussed and untreated, according to a national patient survey.
The online survey was completed by a convenience sample of 1,052 MS patients recruited through the National Multiple Sclerosis Society and other patient advocacy organizations. Fully 88% of the respondents indicated they have lower urinary tract symptoms involving bladder dysfunction and urinary incontinence. The source of these common symptoms in patients with MS is increased contractile activity of the bladder’s detrusor muscle.
The most common lower urinary tract symptom reported by survey respondents was terminal dribble upon voiding, which affected 65% of patients. The next most common symptoms were urinary urgency, experienced by 62%, and incomplete emptying, cited by 61%, Kristin M. Khalaf, Pharm.D., reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Fifty-three percent of patients reported having urgency urinary incontinence, and 45% complained of stress urinary incontinence.
The lower urinary tract symptom that patients found most bothersome was urgency; indeed, one-third of the overall study population indicated they were bothered "quite a bit" or "a great deal" by this problem. Twenty-nine percent of respondents stated they were bothered at least quite a bit by urgency incontinence, added Dr. Khalaf of Allergan, Irvine, Calif.
Only one-third of the 922 MS patients with lower urinary tract symptoms had discussed their symptoms with a health care provider during the past year. When they did speak with a professional, 74% of the time it was with their neurologist. Fifty-two percent spoke to their primary care physician about their problem within the last year.
Among the 42% of survey respondents who indicated they were bothered at least quite a bit by urinary incontinence, 46% hadn’t discussed the problem with a health care provider within the past year, and 35% had never received any form of treatment for it.
Among patients who had ever discussed their lower urinary tract symptoms with a physician or other health care professional, 38% reported currently treating their problem via pelvic exercises or bladder training, 23% were using an oral anticholinergic agent, 4% were taking herbal medicines for their symptoms, 3% were receiving botulinum toxin type A (onabotulinumtoxinA) injections, and 2% had a neural stimulation device.
Most patients currently receiving treatment for their lower urinary tract symptoms pronounced themselves very or somewhat satisfied with their therapy.
The survey was funded by Allergan.
ORLANDO – Lower urinary tract symptoms in patients with multiple sclerosis are common, bothersome, and often undiscussed and untreated, according to a national patient survey.
The online survey was completed by a convenience sample of 1,052 MS patients recruited through the National Multiple Sclerosis Society and other patient advocacy organizations. Fully 88% of the respondents indicated they have lower urinary tract symptoms involving bladder dysfunction and urinary incontinence. The source of these common symptoms in patients with MS is increased contractile activity of the bladder’s detrusor muscle.
The most common lower urinary tract symptom reported by survey respondents was terminal dribble upon voiding, which affected 65% of patients. The next most common symptoms were urinary urgency, experienced by 62%, and incomplete emptying, cited by 61%, Kristin M. Khalaf, Pharm.D., reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Fifty-three percent of patients reported having urgency urinary incontinence, and 45% complained of stress urinary incontinence.
The lower urinary tract symptom that patients found most bothersome was urgency; indeed, one-third of the overall study population indicated they were bothered "quite a bit" or "a great deal" by this problem. Twenty-nine percent of respondents stated they were bothered at least quite a bit by urgency incontinence, added Dr. Khalaf of Allergan, Irvine, Calif.
Only one-third of the 922 MS patients with lower urinary tract symptoms had discussed their symptoms with a health care provider during the past year. When they did speak with a professional, 74% of the time it was with their neurologist. Fifty-two percent spoke to their primary care physician about their problem within the last year.
Among the 42% of survey respondents who indicated they were bothered at least quite a bit by urinary incontinence, 46% hadn’t discussed the problem with a health care provider within the past year, and 35% had never received any form of treatment for it.
Among patients who had ever discussed their lower urinary tract symptoms with a physician or other health care professional, 38% reported currently treating their problem via pelvic exercises or bladder training, 23% were using an oral anticholinergic agent, 4% were taking herbal medicines for their symptoms, 3% were receiving botulinum toxin type A (onabotulinumtoxinA) injections, and 2% had a neural stimulation device.
Most patients currently receiving treatment for their lower urinary tract symptoms pronounced themselves very or somewhat satisfied with their therapy.
The survey was funded by Allergan.
ORLANDO – Lower urinary tract symptoms in patients with multiple sclerosis are common, bothersome, and often undiscussed and untreated, according to a national patient survey.
The online survey was completed by a convenience sample of 1,052 MS patients recruited through the National Multiple Sclerosis Society and other patient advocacy organizations. Fully 88% of the respondents indicated they have lower urinary tract symptoms involving bladder dysfunction and urinary incontinence. The source of these common symptoms in patients with MS is increased contractile activity of the bladder’s detrusor muscle.
The most common lower urinary tract symptom reported by survey respondents was terminal dribble upon voiding, which affected 65% of patients. The next most common symptoms were urinary urgency, experienced by 62%, and incomplete emptying, cited by 61%, Kristin M. Khalaf, Pharm.D., reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Fifty-three percent of patients reported having urgency urinary incontinence, and 45% complained of stress urinary incontinence.
The lower urinary tract symptom that patients found most bothersome was urgency; indeed, one-third of the overall study population indicated they were bothered "quite a bit" or "a great deal" by this problem. Twenty-nine percent of respondents stated they were bothered at least quite a bit by urgency incontinence, added Dr. Khalaf of Allergan, Irvine, Calif.
Only one-third of the 922 MS patients with lower urinary tract symptoms had discussed their symptoms with a health care provider during the past year. When they did speak with a professional, 74% of the time it was with their neurologist. Fifty-two percent spoke to their primary care physician about their problem within the last year.
Among the 42% of survey respondents who indicated they were bothered at least quite a bit by urinary incontinence, 46% hadn’t discussed the problem with a health care provider within the past year, and 35% had never received any form of treatment for it.
Among patients who had ever discussed their lower urinary tract symptoms with a physician or other health care professional, 38% reported currently treating their problem via pelvic exercises or bladder training, 23% were using an oral anticholinergic agent, 4% were taking herbal medicines for their symptoms, 3% were receiving botulinum toxin type A (onabotulinumtoxinA) injections, and 2% had a neural stimulation device.
Most patients currently receiving treatment for their lower urinary tract symptoms pronounced themselves very or somewhat satisfied with their therapy.
The survey was funded by Allergan.
AT THE CMSC/ACTRIMS ANNUAL MEETING
Major Finding: Eighty-eight percent of patients with multiple sclerosis who responded to an online survey indicated they experience lower urinary tract symptoms, but only one-third of those with such symptoms reported having discussed the matter with a physician or other health professional within the past year.
Data Source: The survey included 1,052 respondents, a convenience sample recruited from several patient advocacy organizations.
Disclosures: The study was sponsored by Allergan. The presenter is a company employee.
Evidence of delayed cancer detection in MS patients
ORLANDO – Patients with multiple sclerosis are at significantly reduced risk of being diagnosed with cancer, compared with the general population, but delayed cancer detection – that is, diagnostic neglect – appears to be a contributing factor, a study from British Columbia has shown.
"Diagnostic neglect is unlikely to account for the entire reduced cancer risk that we’re seeing, but I think it could have major implications for the health, well-being, and longevity of people with multiple sclerosis," said Helen Tremlett, Ph.D, a neuroepidemiologist at the University of British Columbia, Vancouver.
In the population-based Malignancy and Multiple Sclerosis (MaMS) study, she and her coinvestigators linked data from the British Columbia MS registry with the provincial cancer registry. The study included 6,820 MS patients who visited a British Columbia MS clinic in 1980-2004. Most had never been exposed to an immunomodulatory therapy. They had a collective 110,666 person-years of follow-up. Their cancer incidence over time was compared with that of the age-, sex-, and calendar year–matched general population of British Columbia.
The standardized incidence ratio for all cancers in the MS cohort was 0.86, meaning MS patients had a highly significant overall 14% reduction in the risk of being diagnosed with cancer. The risk reduction was particularly striking for colorectal cancer: Patients with MS were 44% less likely than controls to be diagnosed with this malignancy.
The cancer risk reductions were similar in men and women with MS, and in those with relapsing-remitting as compared with primary progressive MS, Dr. Tremlett reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Of note, the cancer risk reduction identified in the MaMS study was consistent with an earlier meta-analysis of five studies by other investigators around the world, who concluded that the risk of being diagnosed with cancer was 8% lower in MS patients than controls, a statistically significant difference (J. Neurol. Neurosurg. Psychiatry 2010;81:1413-4).
Unlike the other researchers, however, Dr. Tremlett and her coworkers also looked at tumor size at the time of diagnosis for the four most common cancers: breast, prostate, lung, and colorectal cancer. They found a consistent pattern: MS patients diagnosed with cancer had a lower-than-expected rate of the smaller T1 and T2 tumors than in the matched general population with cancer, and a greater-than-expected rate of T3 and T4 tumors.
The most likely explanation for the observed larger-than-expected tumor size is that when MS patients report, say, a new sense of fatigue, it may be ascribed to their MS, whereas if a patient from the general population had the same complaint, a battery of tests would be ordered, she said.
The MS patients’ 14% reduction in the risk of being diagnosed with cancer had an impressive P value. In contrast, the association between MS and larger tumor size, while statistically significant, had a less than stellar P value of .04. For this reason, Dr. Tremlett said she doesn’t believe diagnostic neglect is the entire explanation for the MS patients’ reduction in cancer incidence. Other possible contributing factors worthy of further study are that MS patients’ hypervigilant immune system renders them less vulnerable to cancer growth, or that MS and cancer share a common and as-yet-unidentified genetic predisposition, or that upon receiving the diagnosis of MS, affected patients adopt a healthier lifestyle.
Dr. Tremlett stressed the importance of being on the lookout for cancer and other aging-related comorbidities, especially now that patients with MS are living longer. In a recent study of 6,917 MS patients in British Columbia, she and her coinvestigators determined that the median survival age was 78.6 years for women and 74.3 years for men. Those are some of the longest life spans ever reported, but still about 6 years less than expected for the general British Columbia population.
Median survival from disease onset was markedly longer for patients with relapsing-onset MS than primary progressive MS: 49.7 years compared with 32.5 years. However, the two groups lived to about the same age.
Patients with primary progressive MS had a 1.52-fold greater relative mortality risk than did those with relapsing-onset MS. Women with primary progressive MS had a 1.55-fold survival disadvantage compared with men with primary progressive disease (J. Neurol. Neurosurg. Psychiatry 2012;83:61-6).
The MaMS study is sponsored by the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada. Dr. Tremlett reported having no relevant financial disclosures.
ORLANDO – Patients with multiple sclerosis are at significantly reduced risk of being diagnosed with cancer, compared with the general population, but delayed cancer detection – that is, diagnostic neglect – appears to be a contributing factor, a study from British Columbia has shown.
"Diagnostic neglect is unlikely to account for the entire reduced cancer risk that we’re seeing, but I think it could have major implications for the health, well-being, and longevity of people with multiple sclerosis," said Helen Tremlett, Ph.D, a neuroepidemiologist at the University of British Columbia, Vancouver.
In the population-based Malignancy and Multiple Sclerosis (MaMS) study, she and her coinvestigators linked data from the British Columbia MS registry with the provincial cancer registry. The study included 6,820 MS patients who visited a British Columbia MS clinic in 1980-2004. Most had never been exposed to an immunomodulatory therapy. They had a collective 110,666 person-years of follow-up. Their cancer incidence over time was compared with that of the age-, sex-, and calendar year–matched general population of British Columbia.
The standardized incidence ratio for all cancers in the MS cohort was 0.86, meaning MS patients had a highly significant overall 14% reduction in the risk of being diagnosed with cancer. The risk reduction was particularly striking for colorectal cancer: Patients with MS were 44% less likely than controls to be diagnosed with this malignancy.
The cancer risk reductions were similar in men and women with MS, and in those with relapsing-remitting as compared with primary progressive MS, Dr. Tremlett reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Of note, the cancer risk reduction identified in the MaMS study was consistent with an earlier meta-analysis of five studies by other investigators around the world, who concluded that the risk of being diagnosed with cancer was 8% lower in MS patients than controls, a statistically significant difference (J. Neurol. Neurosurg. Psychiatry 2010;81:1413-4).
Unlike the other researchers, however, Dr. Tremlett and her coworkers also looked at tumor size at the time of diagnosis for the four most common cancers: breast, prostate, lung, and colorectal cancer. They found a consistent pattern: MS patients diagnosed with cancer had a lower-than-expected rate of the smaller T1 and T2 tumors than in the matched general population with cancer, and a greater-than-expected rate of T3 and T4 tumors.
The most likely explanation for the observed larger-than-expected tumor size is that when MS patients report, say, a new sense of fatigue, it may be ascribed to their MS, whereas if a patient from the general population had the same complaint, a battery of tests would be ordered, she said.
The MS patients’ 14% reduction in the risk of being diagnosed with cancer had an impressive P value. In contrast, the association between MS and larger tumor size, while statistically significant, had a less than stellar P value of .04. For this reason, Dr. Tremlett said she doesn’t believe diagnostic neglect is the entire explanation for the MS patients’ reduction in cancer incidence. Other possible contributing factors worthy of further study are that MS patients’ hypervigilant immune system renders them less vulnerable to cancer growth, or that MS and cancer share a common and as-yet-unidentified genetic predisposition, or that upon receiving the diagnosis of MS, affected patients adopt a healthier lifestyle.
Dr. Tremlett stressed the importance of being on the lookout for cancer and other aging-related comorbidities, especially now that patients with MS are living longer. In a recent study of 6,917 MS patients in British Columbia, she and her coinvestigators determined that the median survival age was 78.6 years for women and 74.3 years for men. Those are some of the longest life spans ever reported, but still about 6 years less than expected for the general British Columbia population.
Median survival from disease onset was markedly longer for patients with relapsing-onset MS than primary progressive MS: 49.7 years compared with 32.5 years. However, the two groups lived to about the same age.
Patients with primary progressive MS had a 1.52-fold greater relative mortality risk than did those with relapsing-onset MS. Women with primary progressive MS had a 1.55-fold survival disadvantage compared with men with primary progressive disease (J. Neurol. Neurosurg. Psychiatry 2012;83:61-6).
The MaMS study is sponsored by the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada. Dr. Tremlett reported having no relevant financial disclosures.
ORLANDO – Patients with multiple sclerosis are at significantly reduced risk of being diagnosed with cancer, compared with the general population, but delayed cancer detection – that is, diagnostic neglect – appears to be a contributing factor, a study from British Columbia has shown.
"Diagnostic neglect is unlikely to account for the entire reduced cancer risk that we’re seeing, but I think it could have major implications for the health, well-being, and longevity of people with multiple sclerosis," said Helen Tremlett, Ph.D, a neuroepidemiologist at the University of British Columbia, Vancouver.
In the population-based Malignancy and Multiple Sclerosis (MaMS) study, she and her coinvestigators linked data from the British Columbia MS registry with the provincial cancer registry. The study included 6,820 MS patients who visited a British Columbia MS clinic in 1980-2004. Most had never been exposed to an immunomodulatory therapy. They had a collective 110,666 person-years of follow-up. Their cancer incidence over time was compared with that of the age-, sex-, and calendar year–matched general population of British Columbia.
The standardized incidence ratio for all cancers in the MS cohort was 0.86, meaning MS patients had a highly significant overall 14% reduction in the risk of being diagnosed with cancer. The risk reduction was particularly striking for colorectal cancer: Patients with MS were 44% less likely than controls to be diagnosed with this malignancy.
The cancer risk reductions were similar in men and women with MS, and in those with relapsing-remitting as compared with primary progressive MS, Dr. Tremlett reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Of note, the cancer risk reduction identified in the MaMS study was consistent with an earlier meta-analysis of five studies by other investigators around the world, who concluded that the risk of being diagnosed with cancer was 8% lower in MS patients than controls, a statistically significant difference (J. Neurol. Neurosurg. Psychiatry 2010;81:1413-4).
Unlike the other researchers, however, Dr. Tremlett and her coworkers also looked at tumor size at the time of diagnosis for the four most common cancers: breast, prostate, lung, and colorectal cancer. They found a consistent pattern: MS patients diagnosed with cancer had a lower-than-expected rate of the smaller T1 and T2 tumors than in the matched general population with cancer, and a greater-than-expected rate of T3 and T4 tumors.
The most likely explanation for the observed larger-than-expected tumor size is that when MS patients report, say, a new sense of fatigue, it may be ascribed to their MS, whereas if a patient from the general population had the same complaint, a battery of tests would be ordered, she said.
The MS patients’ 14% reduction in the risk of being diagnosed with cancer had an impressive P value. In contrast, the association between MS and larger tumor size, while statistically significant, had a less than stellar P value of .04. For this reason, Dr. Tremlett said she doesn’t believe diagnostic neglect is the entire explanation for the MS patients’ reduction in cancer incidence. Other possible contributing factors worthy of further study are that MS patients’ hypervigilant immune system renders them less vulnerable to cancer growth, or that MS and cancer share a common and as-yet-unidentified genetic predisposition, or that upon receiving the diagnosis of MS, affected patients adopt a healthier lifestyle.
Dr. Tremlett stressed the importance of being on the lookout for cancer and other aging-related comorbidities, especially now that patients with MS are living longer. In a recent study of 6,917 MS patients in British Columbia, she and her coinvestigators determined that the median survival age was 78.6 years for women and 74.3 years for men. Those are some of the longest life spans ever reported, but still about 6 years less than expected for the general British Columbia population.
Median survival from disease onset was markedly longer for patients with relapsing-onset MS than primary progressive MS: 49.7 years compared with 32.5 years. However, the two groups lived to about the same age.
Patients with primary progressive MS had a 1.52-fold greater relative mortality risk than did those with relapsing-onset MS. Women with primary progressive MS had a 1.55-fold survival disadvantage compared with men with primary progressive disease (J. Neurol. Neurosurg. Psychiatry 2012;83:61-6).
The MaMS study is sponsored by the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada. Dr. Tremlett reported having no relevant financial disclosures.
AT THE CMSC/ACTRIMS ANNUAL MEETING
Major Finding: Patients with multiple sclerosis in British Columbia had a highly significant 14% reduction in the risk of being diagnosed with cancer, compared with the matched general population. But they also had a larger-than-expected tumor size, suggestive of delayed cancer diagnosis.
Data Source: The population-based Malignancy and Multiple Sclerosis study, which includes 6,820 MS patients with 110,666 person-years of follow-up.
Disclosures: The MaMS study is sponsored by the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada. The presenter reported having no relevant financial disclosures.
Transverse myelitis does not share risk factors with MS
ORLANDO – Epstein-Barr virus exposure and vitamin D insufficiency, which are some of the known risk factors for multiple sclerosis in children and adults, appear not to be associated with transverse myelitis, a small study has shown.
"What we found was that MS risk factors are specific for multiple sclerosis, and not necessarily for all autoimmune demyelinating diseases," said Kelley M. Weinfurtner, a third-year medical student at the University of California, San Francisco (UCSF), who presented a poster detailing the study at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Transverse myelitis (TM) has substantial clinical overlap, especially at early stages, with autoimmune diseases such as multiple sclerosis and neuromyelitis optica, according to Ms. Weinfurtner.
Risk factors for TM are not known, and finding what they are "could be helpful in terms of stratifying when patients come in with TM," and deciding whether the patients would be at risk of MS further down the line, she said.
Ms. Weinfurtner and her colleagues collected blood samples from patients with TM (16), neuromyelitis optica (34), and MS (184) at early stages of disease, and from neurologic controls (95) through the Stony Brook Pediatric MS Center and the Accelerated Cure Project for MS Guthy Jackson Biobank.
They measured serum 25-hydroxyvitamin D levels and checked the blood samples for Epstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV), and HLA-DRB1 allele status.
The median ages at disease onset were 12 years for TM, 11 years for neuromyelitis optica, and 14 years for MS; the median ages at sampling were 30, 16, and 16 years, respectively. The median age of healthy controls at the time of sampling was 16 years.
The majority of the patients were female (61%-70%) and white (all TM patients were white).
The results showed that TM patients were less likely to have been exposed to Epstein-Barr virus, compared with MS patients (odds ratio = 0.021; P less than .001), neuromyelitis optica patients (OR = 0.154; P = .054), and controls (P = .001). TM patients were more likely to have been exposed to HSV-1, although the data did not reach statistical significance.
TM patients also had higher levels of 25-hydroxyvitamin D, compared with MS patients (P = .037) and healthy controls (P = .01).
Meanwhile, there were no significant differences in the frequency of the HLA-DRB1*1501 allele or exposure to cytomegalovirus among TM patients, compared with MS and neuromyelitis optica patients and neurologic controls.
TM patients were significantly older and further from disease onset at the time of the blood draw, but the findings were adjusted for age at the time of the draw. The discrepancy in age "could explain the trend toward higher HSV-1 exposure in TM patients, but only strengthens the findings that TM patients have a lower prevalence of [Epstein-Barr virus] exposure than MS patients," she reported in the poster.
The difference in age could also explain the higher levels of 25-hydroxyvitamin D in TM patients, because they may have been on vitamin D supplementation after diagnosis.
The sample size for the study was small, and TM patients were not stratified by etiology or extent of cord involvement, although they all met criteria for TM, Ms. Weinfurtner said. The investigators were not able to adjust for race or ethnicity, because all TM patients were white.
Her study is not published and she said there’s a need for larger studies to confirm the findings.
Her research was supported by a grant from the Dean’s Office Medical Student Research Program at UCSF. The study is an offshoot of a large, multicenter study conducted by the Pediatric MS Network, which is in the third year of its 5-year period.
On Twitter @NaseemSMiller
ORLANDO – Epstein-Barr virus exposure and vitamin D insufficiency, which are some of the known risk factors for multiple sclerosis in children and adults, appear not to be associated with transverse myelitis, a small study has shown.
"What we found was that MS risk factors are specific for multiple sclerosis, and not necessarily for all autoimmune demyelinating diseases," said Kelley M. Weinfurtner, a third-year medical student at the University of California, San Francisco (UCSF), who presented a poster detailing the study at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Transverse myelitis (TM) has substantial clinical overlap, especially at early stages, with autoimmune diseases such as multiple sclerosis and neuromyelitis optica, according to Ms. Weinfurtner.
Risk factors for TM are not known, and finding what they are "could be helpful in terms of stratifying when patients come in with TM," and deciding whether the patients would be at risk of MS further down the line, she said.
Ms. Weinfurtner and her colleagues collected blood samples from patients with TM (16), neuromyelitis optica (34), and MS (184) at early stages of disease, and from neurologic controls (95) through the Stony Brook Pediatric MS Center and the Accelerated Cure Project for MS Guthy Jackson Biobank.
They measured serum 25-hydroxyvitamin D levels and checked the blood samples for Epstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV), and HLA-DRB1 allele status.
The median ages at disease onset were 12 years for TM, 11 years for neuromyelitis optica, and 14 years for MS; the median ages at sampling were 30, 16, and 16 years, respectively. The median age of healthy controls at the time of sampling was 16 years.
The majority of the patients were female (61%-70%) and white (all TM patients were white).
The results showed that TM patients were less likely to have been exposed to Epstein-Barr virus, compared with MS patients (odds ratio = 0.021; P less than .001), neuromyelitis optica patients (OR = 0.154; P = .054), and controls (P = .001). TM patients were more likely to have been exposed to HSV-1, although the data did not reach statistical significance.
TM patients also had higher levels of 25-hydroxyvitamin D, compared with MS patients (P = .037) and healthy controls (P = .01).
Meanwhile, there were no significant differences in the frequency of the HLA-DRB1*1501 allele or exposure to cytomegalovirus among TM patients, compared with MS and neuromyelitis optica patients and neurologic controls.
TM patients were significantly older and further from disease onset at the time of the blood draw, but the findings were adjusted for age at the time of the draw. The discrepancy in age "could explain the trend toward higher HSV-1 exposure in TM patients, but only strengthens the findings that TM patients have a lower prevalence of [Epstein-Barr virus] exposure than MS patients," she reported in the poster.
The difference in age could also explain the higher levels of 25-hydroxyvitamin D in TM patients, because they may have been on vitamin D supplementation after diagnosis.
The sample size for the study was small, and TM patients were not stratified by etiology or extent of cord involvement, although they all met criteria for TM, Ms. Weinfurtner said. The investigators were not able to adjust for race or ethnicity, because all TM patients were white.
Her study is not published and she said there’s a need for larger studies to confirm the findings.
Her research was supported by a grant from the Dean’s Office Medical Student Research Program at UCSF. The study is an offshoot of a large, multicenter study conducted by the Pediatric MS Network, which is in the third year of its 5-year period.
On Twitter @NaseemSMiller
ORLANDO – Epstein-Barr virus exposure and vitamin D insufficiency, which are some of the known risk factors for multiple sclerosis in children and adults, appear not to be associated with transverse myelitis, a small study has shown.
"What we found was that MS risk factors are specific for multiple sclerosis, and not necessarily for all autoimmune demyelinating diseases," said Kelley M. Weinfurtner, a third-year medical student at the University of California, San Francisco (UCSF), who presented a poster detailing the study at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Transverse myelitis (TM) has substantial clinical overlap, especially at early stages, with autoimmune diseases such as multiple sclerosis and neuromyelitis optica, according to Ms. Weinfurtner.
Risk factors for TM are not known, and finding what they are "could be helpful in terms of stratifying when patients come in with TM," and deciding whether the patients would be at risk of MS further down the line, she said.
Ms. Weinfurtner and her colleagues collected blood samples from patients with TM (16), neuromyelitis optica (34), and MS (184) at early stages of disease, and from neurologic controls (95) through the Stony Brook Pediatric MS Center and the Accelerated Cure Project for MS Guthy Jackson Biobank.
They measured serum 25-hydroxyvitamin D levels and checked the blood samples for Epstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV), and HLA-DRB1 allele status.
The median ages at disease onset were 12 years for TM, 11 years for neuromyelitis optica, and 14 years for MS; the median ages at sampling were 30, 16, and 16 years, respectively. The median age of healthy controls at the time of sampling was 16 years.
The majority of the patients were female (61%-70%) and white (all TM patients were white).
The results showed that TM patients were less likely to have been exposed to Epstein-Barr virus, compared with MS patients (odds ratio = 0.021; P less than .001), neuromyelitis optica patients (OR = 0.154; P = .054), and controls (P = .001). TM patients were more likely to have been exposed to HSV-1, although the data did not reach statistical significance.
TM patients also had higher levels of 25-hydroxyvitamin D, compared with MS patients (P = .037) and healthy controls (P = .01).
Meanwhile, there were no significant differences in the frequency of the HLA-DRB1*1501 allele or exposure to cytomegalovirus among TM patients, compared with MS and neuromyelitis optica patients and neurologic controls.
TM patients were significantly older and further from disease onset at the time of the blood draw, but the findings were adjusted for age at the time of the draw. The discrepancy in age "could explain the trend toward higher HSV-1 exposure in TM patients, but only strengthens the findings that TM patients have a lower prevalence of [Epstein-Barr virus] exposure than MS patients," she reported in the poster.
The difference in age could also explain the higher levels of 25-hydroxyvitamin D in TM patients, because they may have been on vitamin D supplementation after diagnosis.
The sample size for the study was small, and TM patients were not stratified by etiology or extent of cord involvement, although they all met criteria for TM, Ms. Weinfurtner said. The investigators were not able to adjust for race or ethnicity, because all TM patients were white.
Her study is not published and she said there’s a need for larger studies to confirm the findings.
Her research was supported by a grant from the Dean’s Office Medical Student Research Program at UCSF. The study is an offshoot of a large, multicenter study conducted by the Pediatric MS Network, which is in the third year of its 5-year period.
On Twitter @NaseemSMiller
AT THE cmsc/actrims ANNUAL MEETING
Major finding: TM patients were less likely to have been exposed to EBV, compared with MS patients (odds ratio = 0.021; P less than .001), neuromyelitis optica patients (OR = 0.154; P = .054), and controls (P = .001).
Data source: Collected blood samples from patients with TM (16), neuromyelitis optica (34), and MS (184) at early stages of disease, and from neurologic controls (95), through the Stony Brook Pediatric MS Centers and the Accelerated Cure Project for MS/Guthy Jackson Biobank.
Disclosures: Ms. Weinfurtner’s research was supported by a grant from the Dean’s Office Medical Student Research Program at UCSF.
Simvastatin May Reduce Brain Atrophy in Patients With Secondary Progressive MS
SAN DIEGO—Simvastatin may reduce the rate of brain atrophy by approximately 40% in patients with secondary progressive multiple sclerosis (SPMS), according to data presented at the 65th Annual Meeting of the American Academy of Neurology. The effect may be apparent after one year of treatment. Simvastatin also may affect physician- and patient-reported outcomes for these individuals.
Patients Did Not Take MS Drugs
In the MS-STAT trial, Jeremy Chataway, PhD, Consultant Neurologist at the Queen Square MS Centre, National Hospital for Neurology and Neurosurgery in London, and colleagues randomized 140 patients with SPMS in a one-to-one ratio. Patients underwent an MRI at baseline and initially received 40 mg per day of simvastatin or placebo. After one month, the dose was increased to 80 mg, and the treatment continued for two years. One month after the end of treatment, patients underwent a second MRI. The baseline and final MRIs were taken while the patients were off medication to avoid possible pseudoatrophy effects of simvastatin, said Dr. Chataway. The study’s primary outcome was the annualized rate of brain atrophy.
Participants responded to the MS Impact Scale-29 (MSIS-29) at baseline and at 24 months. At the same times, the researchers administered the Expanded Disability Status Scale (EDSS) and MS Functional Composite (MSFC).
At baseline, subjects with SPMS had been actively progressing for at least two years, could walk as far as 500 meters (EDSS 4.0) or at least 20 meters with bilateral assistance (6.5), and had a mean EDSS score of 5.8 and a median EDSS score of 6.0. No patients were taking disease-modifying treatments. Average disease duration was 20 years, and patients had had secondary progression for about seven years. Patients’ mean age was about 50.
Simvastatin Lessened the Impact of MS
More than 90% of patients returned for their second MRI, and a majority of patients were compliant with the medication. The mean rate of change in brain volume was about 0.6% per year among controls, compared with 0.3% per year among patients taking simvastatin.
Approximately 55% of patients taking placebo had higher EDSS scores after two years, compared with 40% of patients in the statin arm. At two years, patients taking simvastatin had lower MSIS-29 scores than patients taking placebo. Simvastatin did not affect MSFC scores, however.
The drug was associated with a 30% reduction in the accumulation of T2 lesions, but the difference was not statistically significant. The researchers found no difference in adverse events or serious adverse events between the two treatment arms.
The statin appeared not to affect any of the T-cell outcomes that the investigators measured. The lack of an effect suggests that simvastatin may work through a vascular, microvascular, or permeability mechanism, concluded Dr. Chataway.
—Erik Greb
Senior Associate Editor
Suggested Reading
Sorensen PS, Lycke J, Erälinna JP, et al. Simvastatin as add-on therapy to interferon b-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691-701.
Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet. 2004;363(9421):1607-1608.
Zamvil SS, Steinman, L. Cholesterol-lowering statins possess anti-inflammatory activity that might be useful for treatment of MS.
SAN DIEGO—Simvastatin may reduce the rate of brain atrophy by approximately 40% in patients with secondary progressive multiple sclerosis (SPMS), according to data presented at the 65th Annual Meeting of the American Academy of Neurology. The effect may be apparent after one year of treatment. Simvastatin also may affect physician- and patient-reported outcomes for these individuals.
Patients Did Not Take MS Drugs
In the MS-STAT trial, Jeremy Chataway, PhD, Consultant Neurologist at the Queen Square MS Centre, National Hospital for Neurology and Neurosurgery in London, and colleagues randomized 140 patients with SPMS in a one-to-one ratio. Patients underwent an MRI at baseline and initially received 40 mg per day of simvastatin or placebo. After one month, the dose was increased to 80 mg, and the treatment continued for two years. One month after the end of treatment, patients underwent a second MRI. The baseline and final MRIs were taken while the patients were off medication to avoid possible pseudoatrophy effects of simvastatin, said Dr. Chataway. The study’s primary outcome was the annualized rate of brain atrophy.
Participants responded to the MS Impact Scale-29 (MSIS-29) at baseline and at 24 months. At the same times, the researchers administered the Expanded Disability Status Scale (EDSS) and MS Functional Composite (MSFC).
At baseline, subjects with SPMS had been actively progressing for at least two years, could walk as far as 500 meters (EDSS 4.0) or at least 20 meters with bilateral assistance (6.5), and had a mean EDSS score of 5.8 and a median EDSS score of 6.0. No patients were taking disease-modifying treatments. Average disease duration was 20 years, and patients had had secondary progression for about seven years. Patients’ mean age was about 50.
Simvastatin Lessened the Impact of MS
More than 90% of patients returned for their second MRI, and a majority of patients were compliant with the medication. The mean rate of change in brain volume was about 0.6% per year among controls, compared with 0.3% per year among patients taking simvastatin.
Approximately 55% of patients taking placebo had higher EDSS scores after two years, compared with 40% of patients in the statin arm. At two years, patients taking simvastatin had lower MSIS-29 scores than patients taking placebo. Simvastatin did not affect MSFC scores, however.
The drug was associated with a 30% reduction in the accumulation of T2 lesions, but the difference was not statistically significant. The researchers found no difference in adverse events or serious adverse events between the two treatment arms.
The statin appeared not to affect any of the T-cell outcomes that the investigators measured. The lack of an effect suggests that simvastatin may work through a vascular, microvascular, or permeability mechanism, concluded Dr. Chataway.
—Erik Greb
Senior Associate Editor
Suggested Reading
Sorensen PS, Lycke J, Erälinna JP, et al. Simvastatin as add-on therapy to interferon b-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691-701.
Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet. 2004;363(9421):1607-1608.
Zamvil SS, Steinman, L. Cholesterol-lowering statins possess anti-inflammatory activity that might be useful for treatment of MS.
SAN DIEGO—Simvastatin may reduce the rate of brain atrophy by approximately 40% in patients with secondary progressive multiple sclerosis (SPMS), according to data presented at the 65th Annual Meeting of the American Academy of Neurology. The effect may be apparent after one year of treatment. Simvastatin also may affect physician- and patient-reported outcomes for these individuals.
Patients Did Not Take MS Drugs
In the MS-STAT trial, Jeremy Chataway, PhD, Consultant Neurologist at the Queen Square MS Centre, National Hospital for Neurology and Neurosurgery in London, and colleagues randomized 140 patients with SPMS in a one-to-one ratio. Patients underwent an MRI at baseline and initially received 40 mg per day of simvastatin or placebo. After one month, the dose was increased to 80 mg, and the treatment continued for two years. One month after the end of treatment, patients underwent a second MRI. The baseline and final MRIs were taken while the patients were off medication to avoid possible pseudoatrophy effects of simvastatin, said Dr. Chataway. The study’s primary outcome was the annualized rate of brain atrophy.
Participants responded to the MS Impact Scale-29 (MSIS-29) at baseline and at 24 months. At the same times, the researchers administered the Expanded Disability Status Scale (EDSS) and MS Functional Composite (MSFC).
At baseline, subjects with SPMS had been actively progressing for at least two years, could walk as far as 500 meters (EDSS 4.0) or at least 20 meters with bilateral assistance (6.5), and had a mean EDSS score of 5.8 and a median EDSS score of 6.0. No patients were taking disease-modifying treatments. Average disease duration was 20 years, and patients had had secondary progression for about seven years. Patients’ mean age was about 50.
Simvastatin Lessened the Impact of MS
More than 90% of patients returned for their second MRI, and a majority of patients were compliant with the medication. The mean rate of change in brain volume was about 0.6% per year among controls, compared with 0.3% per year among patients taking simvastatin.
Approximately 55% of patients taking placebo had higher EDSS scores after two years, compared with 40% of patients in the statin arm. At two years, patients taking simvastatin had lower MSIS-29 scores than patients taking placebo. Simvastatin did not affect MSFC scores, however.
The drug was associated with a 30% reduction in the accumulation of T2 lesions, but the difference was not statistically significant. The researchers found no difference in adverse events or serious adverse events between the two treatment arms.
The statin appeared not to affect any of the T-cell outcomes that the investigators measured. The lack of an effect suggests that simvastatin may work through a vascular, microvascular, or permeability mechanism, concluded Dr. Chataway.
—Erik Greb
Senior Associate Editor
Suggested Reading
Sorensen PS, Lycke J, Erälinna JP, et al. Simvastatin as add-on therapy to interferon b-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691-701.
Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet. 2004;363(9421):1607-1608.
Zamvil SS, Steinman, L. Cholesterol-lowering statins possess anti-inflammatory activity that might be useful for treatment of MS.
Recommendations outline how to improve dimethyl fumarate tolerability
ORLANDO – The flushing frequently reported in conjunction with oral dimethyl fumarate therapy for relapsing forms of multiple sclerosis is greatly reduced by aspirin pretreatment, Dr. J. Theodore Phillips said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
In contrast, slowed titration of dimethyl fumarate (Tecfidera) does not diminish the gastrointestinal adverse effects which are the other common side effect encountered during the first month or two of therapy, added Dr. Phillips, a neurologist in the multiple sclerosis research program at the Baylor Institute for Immunology Research, Dallas.
Dr. Phillips was part of an expert consensus panel which presented recommendations for maximizing the tolerability of dimethyl fumarate, approved earlier this year as the third oral agent for treatment of MS.
In an interview, he said the recommendations are largely based upon expert opinion rather than being rigorously evidence-based guidelines. After the pivotal phase III DEFINE and CONFIRM clinical trials were completed, he and four other study leaders decided to poll the investigators who had enrolled at least 10 patients in the trials as to how they managed the flushing and GI upset problems which arose. The flushing and GI side effects were reported by 36% and 42%, respectively, of study patients randomized to the drug. The incidence decreased after the first month. These side effects were generally rated by investigators as mild-to-moderate in nature. Flushing resulted in study dropout in 2.5% of patients, while another 4.3% discontinued due to GI adverse events.
Thirty of the 84 invited clinical investigators completed the questionnaire. Meanwhile, investigators at Biogen Idec, which markets Tecfidera, conducted their own randomized, double-blind, phase IIIb study in 172 healthy volunteers, the results of which have been incorporated into the expert panel’s recommendations. Participants in the 8-week trial were randomized to one of four treatment arms: dimethyl fumarate titrated in standard fashion over 1 week plus 325 mg of non–enteric-coated aspirin taken 30 minutes beforehand during weeks 1-4, replaced by aspirin placebo in weeks 5-8; dimethyl fumarate plus aspirin placebo during weeks 1-4; dimethyl fumarate slow-titrated over the course of 3 weeks; and double placebo.
Roughly 80% of subjects on dimethyl fumarate without aspirin experienced flushing events, self-assessed as mild-to-moderate. In contrast, while subjects were on both dimethyl fumarate and aspirin, their flushing frequency and severity were similar to participants on double-placebo.
Slow titration of dimethyl fumarate had no impact on GI symptoms or flushing frequency or severity.
Given that slow titration of dimethyl fumarate proved ineffective in reducing GI symptoms in the phase IIIb study, the expert panel’s recommendations for managing nausea/vomiting or abdominal pain were to take the drug with food and consider prescribing a proton pump inhibitor or H2 receptor antagonist. Metoclopramide or domperidone is another recommended option for those with nausea/vomiting. For patients who experience medication-related diarrhea, the panel advised loperamide or other standard antidiarrheal agents.
"Vasocutaneous flushing and GI upset in association with dosing of Tecfidera could for obvious reasons affect a person’s enthusiasm for going on," Dr. Phillips observed. "The main thing is for the physician to set expectations by up-front acknowledging these issues as part of the risk/benefit discussion prior to initiating the drug. Tell the patient that if those side effects were to happen, we’ve got game plans to deal with them."
The investigator survey that formed the basis for the expert panel recommendations was funded by Biogen Idec. Dr. Phillips is on the company’s medical advisory board. He has also received honoraria from Avanir, Genzyme, Novartis, and Teva.
ORLANDO – The flushing frequently reported in conjunction with oral dimethyl fumarate therapy for relapsing forms of multiple sclerosis is greatly reduced by aspirin pretreatment, Dr. J. Theodore Phillips said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
In contrast, slowed titration of dimethyl fumarate (Tecfidera) does not diminish the gastrointestinal adverse effects which are the other common side effect encountered during the first month or two of therapy, added Dr. Phillips, a neurologist in the multiple sclerosis research program at the Baylor Institute for Immunology Research, Dallas.
Dr. Phillips was part of an expert consensus panel which presented recommendations for maximizing the tolerability of dimethyl fumarate, approved earlier this year as the third oral agent for treatment of MS.
In an interview, he said the recommendations are largely based upon expert opinion rather than being rigorously evidence-based guidelines. After the pivotal phase III DEFINE and CONFIRM clinical trials were completed, he and four other study leaders decided to poll the investigators who had enrolled at least 10 patients in the trials as to how they managed the flushing and GI upset problems which arose. The flushing and GI side effects were reported by 36% and 42%, respectively, of study patients randomized to the drug. The incidence decreased after the first month. These side effects were generally rated by investigators as mild-to-moderate in nature. Flushing resulted in study dropout in 2.5% of patients, while another 4.3% discontinued due to GI adverse events.
Thirty of the 84 invited clinical investigators completed the questionnaire. Meanwhile, investigators at Biogen Idec, which markets Tecfidera, conducted their own randomized, double-blind, phase IIIb study in 172 healthy volunteers, the results of which have been incorporated into the expert panel’s recommendations. Participants in the 8-week trial were randomized to one of four treatment arms: dimethyl fumarate titrated in standard fashion over 1 week plus 325 mg of non–enteric-coated aspirin taken 30 minutes beforehand during weeks 1-4, replaced by aspirin placebo in weeks 5-8; dimethyl fumarate plus aspirin placebo during weeks 1-4; dimethyl fumarate slow-titrated over the course of 3 weeks; and double placebo.
Roughly 80% of subjects on dimethyl fumarate without aspirin experienced flushing events, self-assessed as mild-to-moderate. In contrast, while subjects were on both dimethyl fumarate and aspirin, their flushing frequency and severity were similar to participants on double-placebo.
Slow titration of dimethyl fumarate had no impact on GI symptoms or flushing frequency or severity.
Given that slow titration of dimethyl fumarate proved ineffective in reducing GI symptoms in the phase IIIb study, the expert panel’s recommendations for managing nausea/vomiting or abdominal pain were to take the drug with food and consider prescribing a proton pump inhibitor or H2 receptor antagonist. Metoclopramide or domperidone is another recommended option for those with nausea/vomiting. For patients who experience medication-related diarrhea, the panel advised loperamide or other standard antidiarrheal agents.
"Vasocutaneous flushing and GI upset in association with dosing of Tecfidera could for obvious reasons affect a person’s enthusiasm for going on," Dr. Phillips observed. "The main thing is for the physician to set expectations by up-front acknowledging these issues as part of the risk/benefit discussion prior to initiating the drug. Tell the patient that if those side effects were to happen, we’ve got game plans to deal with them."
The investigator survey that formed the basis for the expert panel recommendations was funded by Biogen Idec. Dr. Phillips is on the company’s medical advisory board. He has also received honoraria from Avanir, Genzyme, Novartis, and Teva.
ORLANDO – The flushing frequently reported in conjunction with oral dimethyl fumarate therapy for relapsing forms of multiple sclerosis is greatly reduced by aspirin pretreatment, Dr. J. Theodore Phillips said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
In contrast, slowed titration of dimethyl fumarate (Tecfidera) does not diminish the gastrointestinal adverse effects which are the other common side effect encountered during the first month or two of therapy, added Dr. Phillips, a neurologist in the multiple sclerosis research program at the Baylor Institute for Immunology Research, Dallas.
Dr. Phillips was part of an expert consensus panel which presented recommendations for maximizing the tolerability of dimethyl fumarate, approved earlier this year as the third oral agent for treatment of MS.
In an interview, he said the recommendations are largely based upon expert opinion rather than being rigorously evidence-based guidelines. After the pivotal phase III DEFINE and CONFIRM clinical trials were completed, he and four other study leaders decided to poll the investigators who had enrolled at least 10 patients in the trials as to how they managed the flushing and GI upset problems which arose. The flushing and GI side effects were reported by 36% and 42%, respectively, of study patients randomized to the drug. The incidence decreased after the first month. These side effects were generally rated by investigators as mild-to-moderate in nature. Flushing resulted in study dropout in 2.5% of patients, while another 4.3% discontinued due to GI adverse events.
Thirty of the 84 invited clinical investigators completed the questionnaire. Meanwhile, investigators at Biogen Idec, which markets Tecfidera, conducted their own randomized, double-blind, phase IIIb study in 172 healthy volunteers, the results of which have been incorporated into the expert panel’s recommendations. Participants in the 8-week trial were randomized to one of four treatment arms: dimethyl fumarate titrated in standard fashion over 1 week plus 325 mg of non–enteric-coated aspirin taken 30 minutes beforehand during weeks 1-4, replaced by aspirin placebo in weeks 5-8; dimethyl fumarate plus aspirin placebo during weeks 1-4; dimethyl fumarate slow-titrated over the course of 3 weeks; and double placebo.
Roughly 80% of subjects on dimethyl fumarate without aspirin experienced flushing events, self-assessed as mild-to-moderate. In contrast, while subjects were on both dimethyl fumarate and aspirin, their flushing frequency and severity were similar to participants on double-placebo.
Slow titration of dimethyl fumarate had no impact on GI symptoms or flushing frequency or severity.
Given that slow titration of dimethyl fumarate proved ineffective in reducing GI symptoms in the phase IIIb study, the expert panel’s recommendations for managing nausea/vomiting or abdominal pain were to take the drug with food and consider prescribing a proton pump inhibitor or H2 receptor antagonist. Metoclopramide or domperidone is another recommended option for those with nausea/vomiting. For patients who experience medication-related diarrhea, the panel advised loperamide or other standard antidiarrheal agents.
"Vasocutaneous flushing and GI upset in association with dosing of Tecfidera could for obvious reasons affect a person’s enthusiasm for going on," Dr. Phillips observed. "The main thing is for the physician to set expectations by up-front acknowledging these issues as part of the risk/benefit discussion prior to initiating the drug. Tell the patient that if those side effects were to happen, we’ve got game plans to deal with them."
The investigator survey that formed the basis for the expert panel recommendations was funded by Biogen Idec. Dr. Phillips is on the company’s medical advisory board. He has also received honoraria from Avanir, Genzyme, Novartis, and Teva.
AT THE CMSC/ACTRIMS ANNUAL MEETING
Fingolimod Slows MS Brain Atrophy Within Six Months
SAN DIEGO—Fingolimod slows brain atrophy in patients with multiple sclerosis (MS) and is the only approved drug that does so within the first six months of treatment, reported Jeffrey Cohen, MD, at the 65th Annual Meeting of the American Academy of Neurology.
The findings come from a combined analysis of the drug’s three clinical trials—FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which compared 0.5 mg and 1.25 mg daily against placebo for two years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which compared those doses against weekly intramuscular interferon beta-1a for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation using normalization of atrophy) at baseline and at six, 12, and 24 months. More than 3,000 patients ages 18 to 55 with clinically active relapsing-remitting MS participated.
“There was a consistent” 31% to 36% reduction in the rate of brain volume loss with both doses of fingolimod “compared to placebo and interferon beta-1a,” said Dr. Cohen. “There was no clear-cut dose effect between the two” doses. Dr. Cohen is Director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research, Cleveland Clinic.
In the two trials with placebo arms, patients who had received fingolimod had volume losses of about 0.85%, compared with 1.31% in patients who had received placebo. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The “benefit was seen as early as six months, in both FREEDOMS and FREEDOMS II,” said Dr. Cohen. “In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss—in other words, no pseudoatrophy.”
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab and glatiramer acetate, he noted.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who received it, regardless of baseline characteristics, according to Dr. Cohen.
Weak correlations were observed between accumulations of T2 lesions and disability during the study, perhaps because “brain volume and measures of disability don’t change much over two years,” Dr. Cohen said.
—M. Alexander Otto
IMNG Medical News
SAN DIEGO—Fingolimod slows brain atrophy in patients with multiple sclerosis (MS) and is the only approved drug that does so within the first six months of treatment, reported Jeffrey Cohen, MD, at the 65th Annual Meeting of the American Academy of Neurology.
The findings come from a combined analysis of the drug’s three clinical trials—FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which compared 0.5 mg and 1.25 mg daily against placebo for two years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which compared those doses against weekly intramuscular interferon beta-1a for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation using normalization of atrophy) at baseline and at six, 12, and 24 months. More than 3,000 patients ages 18 to 55 with clinically active relapsing-remitting MS participated.
“There was a consistent” 31% to 36% reduction in the rate of brain volume loss with both doses of fingolimod “compared to placebo and interferon beta-1a,” said Dr. Cohen. “There was no clear-cut dose effect between the two” doses. Dr. Cohen is Director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research, Cleveland Clinic.
In the two trials with placebo arms, patients who had received fingolimod had volume losses of about 0.85%, compared with 1.31% in patients who had received placebo. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The “benefit was seen as early as six months, in both FREEDOMS and FREEDOMS II,” said Dr. Cohen. “In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss—in other words, no pseudoatrophy.”
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab and glatiramer acetate, he noted.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who received it, regardless of baseline characteristics, according to Dr. Cohen.
Weak correlations were observed between accumulations of T2 lesions and disability during the study, perhaps because “brain volume and measures of disability don’t change much over two years,” Dr. Cohen said.
—M. Alexander Otto
IMNG Medical News
SAN DIEGO—Fingolimod slows brain atrophy in patients with multiple sclerosis (MS) and is the only approved drug that does so within the first six months of treatment, reported Jeffrey Cohen, MD, at the 65th Annual Meeting of the American Academy of Neurology.
The findings come from a combined analysis of the drug’s three clinical trials—FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which compared 0.5 mg and 1.25 mg daily against placebo for two years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which compared those doses against weekly intramuscular interferon beta-1a for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation using normalization of atrophy) at baseline and at six, 12, and 24 months. More than 3,000 patients ages 18 to 55 with clinically active relapsing-remitting MS participated.
“There was a consistent” 31% to 36% reduction in the rate of brain volume loss with both doses of fingolimod “compared to placebo and interferon beta-1a,” said Dr. Cohen. “There was no clear-cut dose effect between the two” doses. Dr. Cohen is Director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research, Cleveland Clinic.
In the two trials with placebo arms, patients who had received fingolimod had volume losses of about 0.85%, compared with 1.31% in patients who had received placebo. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The “benefit was seen as early as six months, in both FREEDOMS and FREEDOMS II,” said Dr. Cohen. “In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss—in other words, no pseudoatrophy.”
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab and glatiramer acetate, he noted.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who received it, regardless of baseline characteristics, according to Dr. Cohen.
Weak correlations were observed between accumulations of T2 lesions and disability during the study, perhaps because “brain volume and measures of disability don’t change much over two years,” Dr. Cohen said.
—M. Alexander Otto
IMNG Medical News
Anti-JCV Antibody Index May Further Define PML Risk
ORLANDO—In anti-JCV antibody–positive natalizumab-treated patients with multiple sclerosis (MS) and no prior immunosuppressant (IS) use, a higher anti-JCV antibody index correlates with an increased risk of progressive multifocal leukoencephalopathy (PML), according to research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Tatiana Plavina, PhD, Meena Subramanyam, PhD, and colleagues from Biogen Idec, Inc, examined the association between anti-JCV antibody index (anti-JCV antibody level as measured using the STRATIFY JCV DxSelect assay [Focus Diagnostics, Cypress, California]) and PML risk in anti-JCV–positive patients enrolled in natalizumab clinical studies and from postmarketing settings. Anti-JCV antibody index data were available from 71 natalizumab-treated PML patients at least six months prior to PML diagnosis and from 2,522 non-PML anti-JCV antibody–positive patients.
Low Index, Lower Risk
In cross-sectional analyses, anti-JCV antibody index was not associated with duration of natalizumab treatment (less than or equal to 24 versus more than 24 infusions) or prior IS use but was significantly associated with PML risk. A different relationship was observed between anti-JCV antibody index and PML by prior IS use. Hence, the association between anti-JCV antibody index and PML risk was assessed using all available longitudinal data in anti-JCV–positive patients without prior IS use, and estimated odds ratios across a range of thresholds of interest varied from 7 to 23 for the occurrence of PML at higher versus lower index.
According to previous work by Bloomgren et al, risk of PML in natalizumab-treated anti-JCV antibody–negative patients with MS is less than or equal to 0.1/1000. Anti-JCV antibody–positive patients with no prior IS use who have low anti-JCV antibody index may have severalfold lower PML risk, compared with current risk estimates assigned to all anti-JCV antibody–positive patients with no prior IS use as per the current algorithm. The researchers concluded that “anti-JCV antibody index may further differentiate PML risk for natalizumab-treated anti-JCV antibody–positive MS patients with no prior IS use.”
Stability of the Index Over Time
The researchers also looked at the longitudinal stability of the anti-JCV antibody index. In the AFFIRM and STRATIFY-1 study cohorts, of those patients who tested anti-JCV antibody-negative at baseline, 87% remained consistently negative and 96% remained consistently at lower risk (anti-JCV antibody index less than or equal to 0.9, 1.2, or 1.5) for a period of 18 months, with testing every six months. “These analyses may potentially better inform PML risk in patients who seroconvert or test intermittently positive,” the researchers said. Further, the investigators noted that 96% of natalizumab-treated patients who developed PML and had two or more samples available (n = 25) had pre-PML samples with an index consistently above 0.9.
—Glenn S. Williams
VP/Group Editor
Suggested Reading
Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880.
Lee P Plavina T, Castro A, et al. A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol. 2013;57(2):141-146.
Plavina T, Berman M, Njenga M, et al. Multi-site analytical validation of an assay to detect anti-JCV antibodies in human serum and plasma.
ORLANDO—In anti-JCV antibody–positive natalizumab-treated patients with multiple sclerosis (MS) and no prior immunosuppressant (IS) use, a higher anti-JCV antibody index correlates with an increased risk of progressive multifocal leukoencephalopathy (PML), according to research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Tatiana Plavina, PhD, Meena Subramanyam, PhD, and colleagues from Biogen Idec, Inc, examined the association between anti-JCV antibody index (anti-JCV antibody level as measured using the STRATIFY JCV DxSelect assay [Focus Diagnostics, Cypress, California]) and PML risk in anti-JCV–positive patients enrolled in natalizumab clinical studies and from postmarketing settings. Anti-JCV antibody index data were available from 71 natalizumab-treated PML patients at least six months prior to PML diagnosis and from 2,522 non-PML anti-JCV antibody–positive patients.
Low Index, Lower Risk
In cross-sectional analyses, anti-JCV antibody index was not associated with duration of natalizumab treatment (less than or equal to 24 versus more than 24 infusions) or prior IS use but was significantly associated with PML risk. A different relationship was observed between anti-JCV antibody index and PML by prior IS use. Hence, the association between anti-JCV antibody index and PML risk was assessed using all available longitudinal data in anti-JCV–positive patients without prior IS use, and estimated odds ratios across a range of thresholds of interest varied from 7 to 23 for the occurrence of PML at higher versus lower index.
According to previous work by Bloomgren et al, risk of PML in natalizumab-treated anti-JCV antibody–negative patients with MS is less than or equal to 0.1/1000. Anti-JCV antibody–positive patients with no prior IS use who have low anti-JCV antibody index may have severalfold lower PML risk, compared with current risk estimates assigned to all anti-JCV antibody–positive patients with no prior IS use as per the current algorithm. The researchers concluded that “anti-JCV antibody index may further differentiate PML risk for natalizumab-treated anti-JCV antibody–positive MS patients with no prior IS use.”
Stability of the Index Over Time
The researchers also looked at the longitudinal stability of the anti-JCV antibody index. In the AFFIRM and STRATIFY-1 study cohorts, of those patients who tested anti-JCV antibody-negative at baseline, 87% remained consistently negative and 96% remained consistently at lower risk (anti-JCV antibody index less than or equal to 0.9, 1.2, or 1.5) for a period of 18 months, with testing every six months. “These analyses may potentially better inform PML risk in patients who seroconvert or test intermittently positive,” the researchers said. Further, the investigators noted that 96% of natalizumab-treated patients who developed PML and had two or more samples available (n = 25) had pre-PML samples with an index consistently above 0.9.
—Glenn S. Williams
VP/Group Editor
Suggested Reading
Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880.
Lee P Plavina T, Castro A, et al. A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol. 2013;57(2):141-146.
Plavina T, Berman M, Njenga M, et al. Multi-site analytical validation of an assay to detect anti-JCV antibodies in human serum and plasma.
ORLANDO—In anti-JCV antibody–positive natalizumab-treated patients with multiple sclerosis (MS) and no prior immunosuppressant (IS) use, a higher anti-JCV antibody index correlates with an increased risk of progressive multifocal leukoencephalopathy (PML), according to research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Tatiana Plavina, PhD, Meena Subramanyam, PhD, and colleagues from Biogen Idec, Inc, examined the association between anti-JCV antibody index (anti-JCV antibody level as measured using the STRATIFY JCV DxSelect assay [Focus Diagnostics, Cypress, California]) and PML risk in anti-JCV–positive patients enrolled in natalizumab clinical studies and from postmarketing settings. Anti-JCV antibody index data were available from 71 natalizumab-treated PML patients at least six months prior to PML diagnosis and from 2,522 non-PML anti-JCV antibody–positive patients.
Low Index, Lower Risk
In cross-sectional analyses, anti-JCV antibody index was not associated with duration of natalizumab treatment (less than or equal to 24 versus more than 24 infusions) or prior IS use but was significantly associated with PML risk. A different relationship was observed between anti-JCV antibody index and PML by prior IS use. Hence, the association between anti-JCV antibody index and PML risk was assessed using all available longitudinal data in anti-JCV–positive patients without prior IS use, and estimated odds ratios across a range of thresholds of interest varied from 7 to 23 for the occurrence of PML at higher versus lower index.
According to previous work by Bloomgren et al, risk of PML in natalizumab-treated anti-JCV antibody–negative patients with MS is less than or equal to 0.1/1000. Anti-JCV antibody–positive patients with no prior IS use who have low anti-JCV antibody index may have severalfold lower PML risk, compared with current risk estimates assigned to all anti-JCV antibody–positive patients with no prior IS use as per the current algorithm. The researchers concluded that “anti-JCV antibody index may further differentiate PML risk for natalizumab-treated anti-JCV antibody–positive MS patients with no prior IS use.”
Stability of the Index Over Time
The researchers also looked at the longitudinal stability of the anti-JCV antibody index. In the AFFIRM and STRATIFY-1 study cohorts, of those patients who tested anti-JCV antibody-negative at baseline, 87% remained consistently negative and 96% remained consistently at lower risk (anti-JCV antibody index less than or equal to 0.9, 1.2, or 1.5) for a period of 18 months, with testing every six months. “These analyses may potentially better inform PML risk in patients who seroconvert or test intermittently positive,” the researchers said. Further, the investigators noted that 96% of natalizumab-treated patients who developed PML and had two or more samples available (n = 25) had pre-PML samples with an index consistently above 0.9.
—Glenn S. Williams
VP/Group Editor
Suggested Reading
Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880.
Lee P Plavina T, Castro A, et al. A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol. 2013;57(2):141-146.
Plavina T, Berman M, Njenga M, et al. Multi-site analytical validation of an assay to detect anti-JCV antibodies in human serum and plasma.
News Briefs From the Fifth Cooperative Meeting of CMSC/ACTRIMS
Disease-Modifying Therapies Affect Quality of Life Differently for Men and Women
After three years of disease-modifying therapy (DMT) for multiple sclerosis (MS), physical health-related quality of life (HRQL) declines were experienced by both men and women, but especially in men, according to a study presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Karen V. L. Turpin, MSc, BScN, a PhD student at the University of Alberta in Edmonton, Canada, and colleagues examined the course of changes in HRQL over a three-year period in men and women with relapsing-remitting MS who were being treated with DMTs. The researchers used data from a study of 185 patients with relapsing-remitting MS carried out in Saskatchewan, Canada, that was designed to evaluate the long-term impact of DMTs. Study participants completed the SF-36 HRQL survey at three time points: pre-DMT, follow-up at one year, and follow-up at three years. The researchers investigated the course of changes over time in SF-36 subscale scores and the summary scale scores stratified by sex.
The majority of the sample was female (70.3%). The average age of the sample at the study initiation was 39.2, and the average Expanded Disability Status Scale (EDSS) score was 2.4 (ambulatory with minimal to mild disability). For women, there were initial improvements in all scores at one year. At two years, all scores had decreased and three of the physical health subtest scores (but not the mental health scores) had fallen below initial values. Men showed improvement at one year on role limitations due to physical and mental health problems and on the mental health summary scale. Most men’s gains were retained through year three, but there were substantial declines in the physical HRQL domain scores that were greater than declines experienced by women.
Overall, the researchers found that, compared with pre-DMT scores, there were sustained improvements in mental health at three years, but declines in physical health. Sex differences were apparent in the patterns of improvement and worsening over the course of the three-year follow-up, with the degree of improvement and worsening being especially marked for men. The sustained improvement in mental health scores suggests that, despite a worsening physical health, DMTs may lead to better mental and social health. This is important, the researchers said, because psychosocial well-being has been reported to be the most salient aspect of health for persons with relapsing-remitting MS.
Exercise Training Reduces Fatigue in Patients With MS
Exercise training is associated with a significant moderate reduction in fatigue among patients with multiple sclerosis (MS), according to data presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Lara A. Pilutti, PhD, from the University of Illinois at Urbana-Champaign, and colleagues conducted a meta-analysis to provide a quantitative review of randomized controlled trials examining the effects of exercise training on symptomatic fatigue in persons with MS. Electronic databases (eg, Web of Science, PubMed, PsycINFO, and Google Scholar) were searched for articles published between 1960 and October 2012 using the key words fatigue, tiredness, energy, mood, or lassitude in combination with exercise, physical activity, rehabilitation, or fitness with the additional search term multiple sclerosis. The initial search resulted in 311 articles, of which 74 were reviewed in detail, and 17 met inclusion criteria and provided enough data to compute effect sizes.
The 43 effect sizes from 17 randomized controlled trials with 568 MS participants yielded a weighted mean effect size of 0.45. The weighted mean effect size was slightly heterogeneous. Exploratory moderator analyses indicated that study location, disease duration, training supervision, and mode of exercise might be important variables for understanding the effects of exercise training on symptomatic fatigue.
Overall, exercise training was associated with a significant, nearly one-half standard deviation reduction in symptomatic fatigue among persons with MS. The overall effect size was substantially higher than that reported in other meta-analyses examining the effect of exercise training on walking mobility and quality of life. Further, the researchers reported that the overall effect size found in this study represents a clinically significant change in fatigue with exercise training based on a one-point change in Fatigue Severity Scale scores.
The cumulative evidence supports the association of exercise training with a significant, moderate reduction in fatigue among persons with MS. Based on their findings, the researchers recommend that exercise training should be considered as an effective alternative therapy for the management of fatigue in persons with MS.
Multipotent Adult Progenitor Cells May Become a Viable Treatment for MS
Treatment of patients with multiple sclerosis (MS) with human multipotent adult progenitor cells (MAPCs) may provide clinical benefit through modulation of immune status and promotion of remyelination, according to basic science research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Stem cell therapies are currently being investigated as potential therapeutic treatments for autoimmune disorders such as MS. However, the mechanistic interaction between the diseased tissue environment and transplanted cells is often poorly understood, leading to inefficient or inappropriate applications of cell therapies that may not afford significant health benefits.
Jason A. Hamilton, PhD, from Athersys, Inc, and colleagues investigated the potential use of human MAPCs as a cellular therapeutic for the treatment of MS. Their research evaluated the cells’ efficacy, dose, window of therapeutic benefit, and effects upon remyelination.
Experimental allergic encephalomyelitis (EAE) was induced in C57Bl/6 mice. Efficacy was examined after administering 1, 3, or 9 million cells IV, compared to control animals administered vehicle. Cells or vehicle was administered after significant symptom onset, and behavior was monitored for 28 days by a blinded observer. Window of therapeutic benefit was examined by administering 1 million cells IV at different time points in the course of disease. Myelin content was examined via luxol fast blue (LFB) staining and electron microscopy (EM). Investigation of the direct effects of MAPC upon remyelination was achieved via direct injection of cells or vehicle into lysolecithin (LPC) lesions in adult rat spinal cords. Lesions were characterized via LFB staining and immunocytochemistry.
Significant and sustained behavioral improvement was observed in response to all cell doses tested, when administered after symptom onset. Presymptomatic treatment did not prevent disease onset. Examination of myelination status demonstrated decreased average area of demyelinated lesions in spinal cords of cell-treated animals, as well as a significant decrease in the number of complete lesions. Further analysis via EM showed abundant evidence of newly remyelinated axons within cell-treated animals. Subsequent studies in LPC-lesioned rat spinal cords demonstrated increased remyelination in cell-treated lesions associated with significant induction of M2 macrophages in the core of the lesion.
According to the researchers, the results of their studies suggest that treatment with MAPCs may provide clinical benefit to patients with MS.
—Glenn S. Williams
Vice President, Group Editor
Disease-Modifying Therapies Affect Quality of Life Differently for Men and Women
After three years of disease-modifying therapy (DMT) for multiple sclerosis (MS), physical health-related quality of life (HRQL) declines were experienced by both men and women, but especially in men, according to a study presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Karen V. L. Turpin, MSc, BScN, a PhD student at the University of Alberta in Edmonton, Canada, and colleagues examined the course of changes in HRQL over a three-year period in men and women with relapsing-remitting MS who were being treated with DMTs. The researchers used data from a study of 185 patients with relapsing-remitting MS carried out in Saskatchewan, Canada, that was designed to evaluate the long-term impact of DMTs. Study participants completed the SF-36 HRQL survey at three time points: pre-DMT, follow-up at one year, and follow-up at three years. The researchers investigated the course of changes over time in SF-36 subscale scores and the summary scale scores stratified by sex.
The majority of the sample was female (70.3%). The average age of the sample at the study initiation was 39.2, and the average Expanded Disability Status Scale (EDSS) score was 2.4 (ambulatory with minimal to mild disability). For women, there were initial improvements in all scores at one year. At two years, all scores had decreased and three of the physical health subtest scores (but not the mental health scores) had fallen below initial values. Men showed improvement at one year on role limitations due to physical and mental health problems and on the mental health summary scale. Most men’s gains were retained through year three, but there were substantial declines in the physical HRQL domain scores that were greater than declines experienced by women.
Overall, the researchers found that, compared with pre-DMT scores, there were sustained improvements in mental health at three years, but declines in physical health. Sex differences were apparent in the patterns of improvement and worsening over the course of the three-year follow-up, with the degree of improvement and worsening being especially marked for men. The sustained improvement in mental health scores suggests that, despite a worsening physical health, DMTs may lead to better mental and social health. This is important, the researchers said, because psychosocial well-being has been reported to be the most salient aspect of health for persons with relapsing-remitting MS.
Exercise Training Reduces Fatigue in Patients With MS
Exercise training is associated with a significant moderate reduction in fatigue among patients with multiple sclerosis (MS), according to data presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Lara A. Pilutti, PhD, from the University of Illinois at Urbana-Champaign, and colleagues conducted a meta-analysis to provide a quantitative review of randomized controlled trials examining the effects of exercise training on symptomatic fatigue in persons with MS. Electronic databases (eg, Web of Science, PubMed, PsycINFO, and Google Scholar) were searched for articles published between 1960 and October 2012 using the key words fatigue, tiredness, energy, mood, or lassitude in combination with exercise, physical activity, rehabilitation, or fitness with the additional search term multiple sclerosis. The initial search resulted in 311 articles, of which 74 were reviewed in detail, and 17 met inclusion criteria and provided enough data to compute effect sizes.
The 43 effect sizes from 17 randomized controlled trials with 568 MS participants yielded a weighted mean effect size of 0.45. The weighted mean effect size was slightly heterogeneous. Exploratory moderator analyses indicated that study location, disease duration, training supervision, and mode of exercise might be important variables for understanding the effects of exercise training on symptomatic fatigue.
Overall, exercise training was associated with a significant, nearly one-half standard deviation reduction in symptomatic fatigue among persons with MS. The overall effect size was substantially higher than that reported in other meta-analyses examining the effect of exercise training on walking mobility and quality of life. Further, the researchers reported that the overall effect size found in this study represents a clinically significant change in fatigue with exercise training based on a one-point change in Fatigue Severity Scale scores.
The cumulative evidence supports the association of exercise training with a significant, moderate reduction in fatigue among persons with MS. Based on their findings, the researchers recommend that exercise training should be considered as an effective alternative therapy for the management of fatigue in persons with MS.
Multipotent Adult Progenitor Cells May Become a Viable Treatment for MS
Treatment of patients with multiple sclerosis (MS) with human multipotent adult progenitor cells (MAPCs) may provide clinical benefit through modulation of immune status and promotion of remyelination, according to basic science research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Stem cell therapies are currently being investigated as potential therapeutic treatments for autoimmune disorders such as MS. However, the mechanistic interaction between the diseased tissue environment and transplanted cells is often poorly understood, leading to inefficient or inappropriate applications of cell therapies that may not afford significant health benefits.
Jason A. Hamilton, PhD, from Athersys, Inc, and colleagues investigated the potential use of human MAPCs as a cellular therapeutic for the treatment of MS. Their research evaluated the cells’ efficacy, dose, window of therapeutic benefit, and effects upon remyelination.
Experimental allergic encephalomyelitis (EAE) was induced in C57Bl/6 mice. Efficacy was examined after administering 1, 3, or 9 million cells IV, compared to control animals administered vehicle. Cells or vehicle was administered after significant symptom onset, and behavior was monitored for 28 days by a blinded observer. Window of therapeutic benefit was examined by administering 1 million cells IV at different time points in the course of disease. Myelin content was examined via luxol fast blue (LFB) staining and electron microscopy (EM). Investigation of the direct effects of MAPC upon remyelination was achieved via direct injection of cells or vehicle into lysolecithin (LPC) lesions in adult rat spinal cords. Lesions were characterized via LFB staining and immunocytochemistry.
Significant and sustained behavioral improvement was observed in response to all cell doses tested, when administered after symptom onset. Presymptomatic treatment did not prevent disease onset. Examination of myelination status demonstrated decreased average area of demyelinated lesions in spinal cords of cell-treated animals, as well as a significant decrease in the number of complete lesions. Further analysis via EM showed abundant evidence of newly remyelinated axons within cell-treated animals. Subsequent studies in LPC-lesioned rat spinal cords demonstrated increased remyelination in cell-treated lesions associated with significant induction of M2 macrophages in the core of the lesion.
According to the researchers, the results of their studies suggest that treatment with MAPCs may provide clinical benefit to patients with MS.
—Glenn S. Williams
Vice President, Group Editor
Disease-Modifying Therapies Affect Quality of Life Differently for Men and Women
After three years of disease-modifying therapy (DMT) for multiple sclerosis (MS), physical health-related quality of life (HRQL) declines were experienced by both men and women, but especially in men, according to a study presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Karen V. L. Turpin, MSc, BScN, a PhD student at the University of Alberta in Edmonton, Canada, and colleagues examined the course of changes in HRQL over a three-year period in men and women with relapsing-remitting MS who were being treated with DMTs. The researchers used data from a study of 185 patients with relapsing-remitting MS carried out in Saskatchewan, Canada, that was designed to evaluate the long-term impact of DMTs. Study participants completed the SF-36 HRQL survey at three time points: pre-DMT, follow-up at one year, and follow-up at three years. The researchers investigated the course of changes over time in SF-36 subscale scores and the summary scale scores stratified by sex.
The majority of the sample was female (70.3%). The average age of the sample at the study initiation was 39.2, and the average Expanded Disability Status Scale (EDSS) score was 2.4 (ambulatory with minimal to mild disability). For women, there were initial improvements in all scores at one year. At two years, all scores had decreased and three of the physical health subtest scores (but not the mental health scores) had fallen below initial values. Men showed improvement at one year on role limitations due to physical and mental health problems and on the mental health summary scale. Most men’s gains were retained through year three, but there were substantial declines in the physical HRQL domain scores that were greater than declines experienced by women.
Overall, the researchers found that, compared with pre-DMT scores, there were sustained improvements in mental health at three years, but declines in physical health. Sex differences were apparent in the patterns of improvement and worsening over the course of the three-year follow-up, with the degree of improvement and worsening being especially marked for men. The sustained improvement in mental health scores suggests that, despite a worsening physical health, DMTs may lead to better mental and social health. This is important, the researchers said, because psychosocial well-being has been reported to be the most salient aspect of health for persons with relapsing-remitting MS.
Exercise Training Reduces Fatigue in Patients With MS
Exercise training is associated with a significant moderate reduction in fatigue among patients with multiple sclerosis (MS), according to data presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Lara A. Pilutti, PhD, from the University of Illinois at Urbana-Champaign, and colleagues conducted a meta-analysis to provide a quantitative review of randomized controlled trials examining the effects of exercise training on symptomatic fatigue in persons with MS. Electronic databases (eg, Web of Science, PubMed, PsycINFO, and Google Scholar) were searched for articles published between 1960 and October 2012 using the key words fatigue, tiredness, energy, mood, or lassitude in combination with exercise, physical activity, rehabilitation, or fitness with the additional search term multiple sclerosis. The initial search resulted in 311 articles, of which 74 were reviewed in detail, and 17 met inclusion criteria and provided enough data to compute effect sizes.
The 43 effect sizes from 17 randomized controlled trials with 568 MS participants yielded a weighted mean effect size of 0.45. The weighted mean effect size was slightly heterogeneous. Exploratory moderator analyses indicated that study location, disease duration, training supervision, and mode of exercise might be important variables for understanding the effects of exercise training on symptomatic fatigue.
Overall, exercise training was associated with a significant, nearly one-half standard deviation reduction in symptomatic fatigue among persons with MS. The overall effect size was substantially higher than that reported in other meta-analyses examining the effect of exercise training on walking mobility and quality of life. Further, the researchers reported that the overall effect size found in this study represents a clinically significant change in fatigue with exercise training based on a one-point change in Fatigue Severity Scale scores.
The cumulative evidence supports the association of exercise training with a significant, moderate reduction in fatigue among persons with MS. Based on their findings, the researchers recommend that exercise training should be considered as an effective alternative therapy for the management of fatigue in persons with MS.
Multipotent Adult Progenitor Cells May Become a Viable Treatment for MS
Treatment of patients with multiple sclerosis (MS) with human multipotent adult progenitor cells (MAPCs) may provide clinical benefit through modulation of immune status and promotion of remyelination, according to basic science research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Stem cell therapies are currently being investigated as potential therapeutic treatments for autoimmune disorders such as MS. However, the mechanistic interaction between the diseased tissue environment and transplanted cells is often poorly understood, leading to inefficient or inappropriate applications of cell therapies that may not afford significant health benefits.
Jason A. Hamilton, PhD, from Athersys, Inc, and colleagues investigated the potential use of human MAPCs as a cellular therapeutic for the treatment of MS. Their research evaluated the cells’ efficacy, dose, window of therapeutic benefit, and effects upon remyelination.
Experimental allergic encephalomyelitis (EAE) was induced in C57Bl/6 mice. Efficacy was examined after administering 1, 3, or 9 million cells IV, compared to control animals administered vehicle. Cells or vehicle was administered after significant symptom onset, and behavior was monitored for 28 days by a blinded observer. Window of therapeutic benefit was examined by administering 1 million cells IV at different time points in the course of disease. Myelin content was examined via luxol fast blue (LFB) staining and electron microscopy (EM). Investigation of the direct effects of MAPC upon remyelination was achieved via direct injection of cells or vehicle into lysolecithin (LPC) lesions in adult rat spinal cords. Lesions were characterized via LFB staining and immunocytochemistry.
Significant and sustained behavioral improvement was observed in response to all cell doses tested, when administered after symptom onset. Presymptomatic treatment did not prevent disease onset. Examination of myelination status demonstrated decreased average area of demyelinated lesions in spinal cords of cell-treated animals, as well as a significant decrease in the number of complete lesions. Further analysis via EM showed abundant evidence of newly remyelinated axons within cell-treated animals. Subsequent studies in LPC-lesioned rat spinal cords demonstrated increased remyelination in cell-treated lesions associated with significant induction of M2 macrophages in the core of the lesion.
According to the researchers, the results of their studies suggest that treatment with MAPCs may provide clinical benefit to patients with MS.
—Glenn S. Williams
Vice President, Group Editor
Tool May Identify Risk of Transition to Secondary Progressive MS
SAN DIEGO—A new statistical model may be able to estimate a patient’s current risk of progressing from relapsing-remitting multiple sclerosis (MS) to secondary progressive MS. If future investigations prove the model robust, it eventually may help select high-risk patients for clinical trials and aid in the design of trials in which secondary progressive MS is an outcome, said Helen Tedeholm, MSci, a doctoral student at the University of Gothenburg in Sweden.
At the 65th Annual Meeting of the American Academy of Neurology, Ms. Tedeholm and colleagues presented their study of 157 untreated patients diagnosed with relapsing-remitting MS according to the Poser criteria. All patients had had a distinct second relapse of the disease and were followed up for more than 45 years.
The researchers created Poisson regression models with secondary progressive MS as an outcome using previously validated clinical characteristics as variables. The variables were confirmed for each patient as they arose at any time during the course of relapsing-remitting MS.
Of the original cohort, 118 patients developed secondary progressive MS. The risk of secondary progressive MS peaked when the patients were approximately age 30. Three of the variables that the investigators tested—current age, severity of the last relapse, and time since the last relapse—were independently significant predictors of transition to secondary progressive MS.
Ms. Tedeholm and colleagues developed a statistical model that included information from the second relapse onward, as well as the time and clinical characteristics of relapses. The risk of transition to secondary progressive MS increased sharply with a relapse with a high severity score, but it decreased with a relapse with a low severity score.
By applying the model to individual patients, the researchers calculated their current risk of developing secondary progressive MS. Among the study participants, 40 had the highest risk of progressive MS (greater than 0.14 events/year), and 41 had the lowest risk (less than 0.015 events/year).
—Erik Greb
Senior Associate Editor
Suggested Reading
Martinelli-Boneschi F, Esposito F, Brambilla P, et al. A genome-wide association study in progressive multiple sclerosis. Mult Scler. 2012;18(10):1384-1394. Roudbari SA, Ansar MM, Yousefzad A. Smoking as a risk factor for development of secondary progressive multiple sclerosis: A study in IRAN, Guilan. J Neurol Sci. 2013 Apr 26 [Epub ahead of print].
SAN DIEGO—A new statistical model may be able to estimate a patient’s current risk of progressing from relapsing-remitting multiple sclerosis (MS) to secondary progressive MS. If future investigations prove the model robust, it eventually may help select high-risk patients for clinical trials and aid in the design of trials in which secondary progressive MS is an outcome, said Helen Tedeholm, MSci, a doctoral student at the University of Gothenburg in Sweden.
At the 65th Annual Meeting of the American Academy of Neurology, Ms. Tedeholm and colleagues presented their study of 157 untreated patients diagnosed with relapsing-remitting MS according to the Poser criteria. All patients had had a distinct second relapse of the disease and were followed up for more than 45 years.
The researchers created Poisson regression models with secondary progressive MS as an outcome using previously validated clinical characteristics as variables. The variables were confirmed for each patient as they arose at any time during the course of relapsing-remitting MS.
Of the original cohort, 118 patients developed secondary progressive MS. The risk of secondary progressive MS peaked when the patients were approximately age 30. Three of the variables that the investigators tested—current age, severity of the last relapse, and time since the last relapse—were independently significant predictors of transition to secondary progressive MS.
Ms. Tedeholm and colleagues developed a statistical model that included information from the second relapse onward, as well as the time and clinical characteristics of relapses. The risk of transition to secondary progressive MS increased sharply with a relapse with a high severity score, but it decreased with a relapse with a low severity score.
By applying the model to individual patients, the researchers calculated their current risk of developing secondary progressive MS. Among the study participants, 40 had the highest risk of progressive MS (greater than 0.14 events/year), and 41 had the lowest risk (less than 0.015 events/year).
—Erik Greb
Senior Associate Editor
Suggested Reading
Martinelli-Boneschi F, Esposito F, Brambilla P, et al. A genome-wide association study in progressive multiple sclerosis. Mult Scler. 2012;18(10):1384-1394. Roudbari SA, Ansar MM, Yousefzad A. Smoking as a risk factor for development of secondary progressive multiple sclerosis: A study in IRAN, Guilan. J Neurol Sci. 2013 Apr 26 [Epub ahead of print].
SAN DIEGO—A new statistical model may be able to estimate a patient’s current risk of progressing from relapsing-remitting multiple sclerosis (MS) to secondary progressive MS. If future investigations prove the model robust, it eventually may help select high-risk patients for clinical trials and aid in the design of trials in which secondary progressive MS is an outcome, said Helen Tedeholm, MSci, a doctoral student at the University of Gothenburg in Sweden.
At the 65th Annual Meeting of the American Academy of Neurology, Ms. Tedeholm and colleagues presented their study of 157 untreated patients diagnosed with relapsing-remitting MS according to the Poser criteria. All patients had had a distinct second relapse of the disease and were followed up for more than 45 years.
The researchers created Poisson regression models with secondary progressive MS as an outcome using previously validated clinical characteristics as variables. The variables were confirmed for each patient as they arose at any time during the course of relapsing-remitting MS.
Of the original cohort, 118 patients developed secondary progressive MS. The risk of secondary progressive MS peaked when the patients were approximately age 30. Three of the variables that the investigators tested—current age, severity of the last relapse, and time since the last relapse—were independently significant predictors of transition to secondary progressive MS.
Ms. Tedeholm and colleagues developed a statistical model that included information from the second relapse onward, as well as the time and clinical characteristics of relapses. The risk of transition to secondary progressive MS increased sharply with a relapse with a high severity score, but it decreased with a relapse with a low severity score.
By applying the model to individual patients, the researchers calculated their current risk of developing secondary progressive MS. Among the study participants, 40 had the highest risk of progressive MS (greater than 0.14 events/year), and 41 had the lowest risk (less than 0.015 events/year).
—Erik Greb
Senior Associate Editor
Suggested Reading
Martinelli-Boneschi F, Esposito F, Brambilla P, et al. A genome-wide association study in progressive multiple sclerosis. Mult Scler. 2012;18(10):1384-1394. Roudbari SA, Ansar MM, Yousefzad A. Smoking as a risk factor for development of secondary progressive multiple sclerosis: A study in IRAN, Guilan. J Neurol Sci. 2013 Apr 26 [Epub ahead of print].