CMSC 2013

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.

bjancin@frontlinemedcom.com

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.

bjancin@frontlinemedcom.com

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.

bjancin@frontlinemedcom.com

ORLANDO – The anti-JC virus antibody index appears to be an important new tool in further delineating the risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis patients, according to Dr. Patricia K. Coyle.

Indeed, progressive multifocal leukoencephalopathy (PML) risk stratification could very well transform natalizumab (Tysabri) from a second-line agent for relapsing forms of MS to first-line therapy, she predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

After all, it’s widely accepted that natalizumab is the most effective of all the Food and Drug Administration–approved treatments for MS. And adherence is a nonissue, since the medication has to be given monthly at an infusion center. Natalizumab is clearly the preferred agent for patients with highly active disease, those with a poor prognosis, and African Americans, because the databases demonstrate they respond so well to it.

"The only thing holding back natalizumab from first-line treatment status is the PML risk. But there’s afoot the possibility of considering natalizumab as a first-line agent by risk-stratifying patients," explained Dr. Coyle, professor of neurology and director of the MS comprehensive care center at Stony Brook (N.Y.) Medical Center.

It’s increasingly clear that an individual’s risk level can be refined on the basis of three factors: anti-JC virus antibody status, natalizumab treatment duration, and a history of prior immunosuppressive therapy.

The JC virus is a ubiquitous DNA polyomavirus shed in the urine of 25% of normal individuals. Up to 70% of the general population is seropositive. It’s ordinarily a benign virus, yet it’s a requirement for developing PML.

An analysis of large clinical trial databases indicates that anti-JC virus antibody–negative MS patients on natalizumab have a reassuringly low risk of developing PML: roughly 1 in 10,000. The good news is that antibody-positive patients with a low antibody index appear to have a similarly low risk.

In an analysis presented at the CMSC/ACTRIMS meeting by Dr. Tatiana Plavina and Dr. Meena Subramanyam of Biogen Idec, Weston, Mass., the investigators estimated the risk of PML in anti-JC virus antibody–positive patients with an antibody index of 0.9 or less at 1 in 10,000 patients during their first 24 months on natalizumab, inching up to 3 per 10,000 with 25-40 months of use, and 4 per 10,000 with 49-72 months of use.

In contrast, the PML risk in anti-JC virus antibody–positive patients with an antibody index above 1.5 was 10 per 10,000 during the first 24 months, 81 per 10,000 with 25-48 months on natalizumab, and 85 per 10,000 with 49-72 months. These risk estimates were based on analysis of close to 6,000 blood samples from 51 natalizumab users who developed PML and 2,242 others who didn’t.

"This needs to be confirmed in other large databases. If this holds up, measuring the antibody index is going to be something we’ll routinely be doing," Dr. Coyle commented.

In fact, she’s already doing it in her own practice. She now checks the anti-JC virus antibody status of her antibody-negative patients on natalizumab every 3 months.

"The goal is to identify PML at an early asymptomatic stage," she noted.

If a patient turns positive, she obtains the antibody index and uses it to guide patient management. The antibody index reflects antibody titers but is a more reliable measure. The antibody index is easily measured using a commercially available kit. Typically, the index appears to persist at the same level – low or high risk – for an extended period.

An important caveat about the anti-JC virus antibody index as a risk stratification tool is that it doesn’t work if a patient has had prior immunosuppressive therapy of any type, even if only for a relatively brief time.

"All bets are off if you have prior immunosuppression. You can’t use the risk figures. This speaks to the importance of carefully staging your therapies," according to the neurologist.

Although the risk of PML appears to rise after about 2 years on natalizumab, in her view there’s nothing magic about that time line. In an anti-JC virus antibody–positive patient with a low antibody index who wants to continue on natalizumab after being fully informed of the risks as understood today, Dr. Coyle is willing to do so. Under those circumstances she suggests backing off from infusions every 4 weeks to a 6- to 8-week schedule, with MRIs every 4 months instead of 6.

"There are no data to show backing off in this way reduces PML risk, but I think it’s rational," she explained.

Natalizumab is such an effective agent that if a patient with MS experiences breakthrough disease activity on the drug, it’s time to check for the possible presence of neutralizing antibodies to natalizumab.

"We have very good data that if somebody has formed persistent neutralizing antibodies, the drug is not working. And there’s no point in putting a patient at any extra risk for a drug that is not working," Dr. Coyle said.

A significant infusion reaction is another indicator that neutralizing antibodies may be present, she added.

What does the future hold for natalizumab?

Dr. Coyle predicted that in the short term the drug will see increasing use as physicians become comfortable with risk stratification as a means of identifying the portion of the MS population at low risk for PML. But she forecast that several years from now this highly effective medication will have fallen by the wayside.

"I think the era of natalizumab is ending," she said. "In my opinion it’s going to be supplanted by anti-CD20 agents in the next couple of years – drugs with equivalent efficacy and greater safety."

She reported having received honoraria from Biogen Idec and eight other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – The anti-JC virus antibody index appears to be an important new tool in further delineating the risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis patients, according to Dr. Patricia K. Coyle.

Indeed, progressive multifocal leukoencephalopathy (PML) risk stratification could very well transform natalizumab (Tysabri) from a second-line agent for relapsing forms of MS to first-line therapy, she predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

After all, it’s widely accepted that natalizumab is the most effective of all the Food and Drug Administration–approved treatments for MS. And adherence is a nonissue, since the medication has to be given monthly at an infusion center. Natalizumab is clearly the preferred agent for patients with highly active disease, those with a poor prognosis, and African Americans, because the databases demonstrate they respond so well to it.

"The only thing holding back natalizumab from first-line treatment status is the PML risk. But there’s afoot the possibility of considering natalizumab as a first-line agent by risk-stratifying patients," explained Dr. Coyle, professor of neurology and director of the MS comprehensive care center at Stony Brook (N.Y.) Medical Center.

It’s increasingly clear that an individual’s risk level can be refined on the basis of three factors: anti-JC virus antibody status, natalizumab treatment duration, and a history of prior immunosuppressive therapy.

The JC virus is a ubiquitous DNA polyomavirus shed in the urine of 25% of normal individuals. Up to 70% of the general population is seropositive. It’s ordinarily a benign virus, yet it’s a requirement for developing PML.

An analysis of large clinical trial databases indicates that anti-JC virus antibody–negative MS patients on natalizumab have a reassuringly low risk of developing PML: roughly 1 in 10,000. The good news is that antibody-positive patients with a low antibody index appear to have a similarly low risk.

In an analysis presented at the CMSC/ACTRIMS meeting by Dr. Tatiana Plavina and Dr. Meena Subramanyam of Biogen Idec, Weston, Mass., the investigators estimated the risk of PML in anti-JC virus antibody–positive patients with an antibody index of 0.9 or less at 1 in 10,000 patients during their first 24 months on natalizumab, inching up to 3 per 10,000 with 25-40 months of use, and 4 per 10,000 with 49-72 months of use.

In contrast, the PML risk in anti-JC virus antibody–positive patients with an antibody index above 1.5 was 10 per 10,000 during the first 24 months, 81 per 10,000 with 25-48 months on natalizumab, and 85 per 10,000 with 49-72 months. These risk estimates were based on analysis of close to 6,000 blood samples from 51 natalizumab users who developed PML and 2,242 others who didn’t.

"This needs to be confirmed in other large databases. If this holds up, measuring the antibody index is going to be something we’ll routinely be doing," Dr. Coyle commented.

In fact, she’s already doing it in her own practice. She now checks the anti-JC virus antibody status of her antibody-negative patients on natalizumab every 3 months.

"The goal is to identify PML at an early asymptomatic stage," she noted.

If a patient turns positive, she obtains the antibody index and uses it to guide patient management. The antibody index reflects antibody titers but is a more reliable measure. The antibody index is easily measured using a commercially available kit. Typically, the index appears to persist at the same level – low or high risk – for an extended period.

An important caveat about the anti-JC virus antibody index as a risk stratification tool is that it doesn’t work if a patient has had prior immunosuppressive therapy of any type, even if only for a relatively brief time.

"All bets are off if you have prior immunosuppression. You can’t use the risk figures. This speaks to the importance of carefully staging your therapies," according to the neurologist.

Although the risk of PML appears to rise after about 2 years on natalizumab, in her view there’s nothing magic about that time line. In an anti-JC virus antibody–positive patient with a low antibody index who wants to continue on natalizumab after being fully informed of the risks as understood today, Dr. Coyle is willing to do so. Under those circumstances she suggests backing off from infusions every 4 weeks to a 6- to 8-week schedule, with MRIs every 4 months instead of 6.

"There are no data to show backing off in this way reduces PML risk, but I think it’s rational," she explained.

Natalizumab is such an effective agent that if a patient with MS experiences breakthrough disease activity on the drug, it’s time to check for the possible presence of neutralizing antibodies to natalizumab.

"We have very good data that if somebody has formed persistent neutralizing antibodies, the drug is not working. And there’s no point in putting a patient at any extra risk for a drug that is not working," Dr. Coyle said.

A significant infusion reaction is another indicator that neutralizing antibodies may be present, she added.

What does the future hold for natalizumab?

Dr. Coyle predicted that in the short term the drug will see increasing use as physicians become comfortable with risk stratification as a means of identifying the portion of the MS population at low risk for PML. But she forecast that several years from now this highly effective medication will have fallen by the wayside.

"I think the era of natalizumab is ending," she said. "In my opinion it’s going to be supplanted by anti-CD20 agents in the next couple of years – drugs with equivalent efficacy and greater safety."

She reported having received honoraria from Biogen Idec and eight other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – The anti-JC virus antibody index appears to be an important new tool in further delineating the risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis patients, according to Dr. Patricia K. Coyle.

Indeed, progressive multifocal leukoencephalopathy (PML) risk stratification could very well transform natalizumab (Tysabri) from a second-line agent for relapsing forms of MS to first-line therapy, she predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

After all, it’s widely accepted that natalizumab is the most effective of all the Food and Drug Administration–approved treatments for MS. And adherence is a nonissue, since the medication has to be given monthly at an infusion center. Natalizumab is clearly the preferred agent for patients with highly active disease, those with a poor prognosis, and African Americans, because the databases demonstrate they respond so well to it.

"The only thing holding back natalizumab from first-line treatment status is the PML risk. But there’s afoot the possibility of considering natalizumab as a first-line agent by risk-stratifying patients," explained Dr. Coyle, professor of neurology and director of the MS comprehensive care center at Stony Brook (N.Y.) Medical Center.

It’s increasingly clear that an individual’s risk level can be refined on the basis of three factors: anti-JC virus antibody status, natalizumab treatment duration, and a history of prior immunosuppressive therapy.

The JC virus is a ubiquitous DNA polyomavirus shed in the urine of 25% of normal individuals. Up to 70% of the general population is seropositive. It’s ordinarily a benign virus, yet it’s a requirement for developing PML.

An analysis of large clinical trial databases indicates that anti-JC virus antibody–negative MS patients on natalizumab have a reassuringly low risk of developing PML: roughly 1 in 10,000. The good news is that antibody-positive patients with a low antibody index appear to have a similarly low risk.

In an analysis presented at the CMSC/ACTRIMS meeting by Dr. Tatiana Plavina and Dr. Meena Subramanyam of Biogen Idec, Weston, Mass., the investigators estimated the risk of PML in anti-JC virus antibody–positive patients with an antibody index of 0.9 or less at 1 in 10,000 patients during their first 24 months on natalizumab, inching up to 3 per 10,000 with 25-40 months of use, and 4 per 10,000 with 49-72 months of use.

In contrast, the PML risk in anti-JC virus antibody–positive patients with an antibody index above 1.5 was 10 per 10,000 during the first 24 months, 81 per 10,000 with 25-48 months on natalizumab, and 85 per 10,000 with 49-72 months. These risk estimates were based on analysis of close to 6,000 blood samples from 51 natalizumab users who developed PML and 2,242 others who didn’t.

"This needs to be confirmed in other large databases. If this holds up, measuring the antibody index is going to be something we’ll routinely be doing," Dr. Coyle commented.

In fact, she’s already doing it in her own practice. She now checks the anti-JC virus antibody status of her antibody-negative patients on natalizumab every 3 months.

"The goal is to identify PML at an early asymptomatic stage," she noted.

If a patient turns positive, she obtains the antibody index and uses it to guide patient management. The antibody index reflects antibody titers but is a more reliable measure. The antibody index is easily measured using a commercially available kit. Typically, the index appears to persist at the same level – low or high risk – for an extended period.

An important caveat about the anti-JC virus antibody index as a risk stratification tool is that it doesn’t work if a patient has had prior immunosuppressive therapy of any type, even if only for a relatively brief time.

"All bets are off if you have prior immunosuppression. You can’t use the risk figures. This speaks to the importance of carefully staging your therapies," according to the neurologist.

Although the risk of PML appears to rise after about 2 years on natalizumab, in her view there’s nothing magic about that time line. In an anti-JC virus antibody–positive patient with a low antibody index who wants to continue on natalizumab after being fully informed of the risks as understood today, Dr. Coyle is willing to do so. Under those circumstances she suggests backing off from infusions every 4 weeks to a 6- to 8-week schedule, with MRIs every 4 months instead of 6.

"There are no data to show backing off in this way reduces PML risk, but I think it’s rational," she explained.

Natalizumab is such an effective agent that if a patient with MS experiences breakthrough disease activity on the drug, it’s time to check for the possible presence of neutralizing antibodies to natalizumab.

"We have very good data that if somebody has formed persistent neutralizing antibodies, the drug is not working. And there’s no point in putting a patient at any extra risk for a drug that is not working," Dr. Coyle said.

A significant infusion reaction is another indicator that neutralizing antibodies may be present, she added.

What does the future hold for natalizumab?

Dr. Coyle predicted that in the short term the drug will see increasing use as physicians become comfortable with risk stratification as a means of identifying the portion of the MS population at low risk for PML. But she forecast that several years from now this highly effective medication will have fallen by the wayside.

"I think the era of natalizumab is ending," she said. "In my opinion it’s going to be supplanted by anti-CD20 agents in the next couple of years – drugs with equivalent efficacy and greater safety."

She reported having received honoraria from Biogen Idec and eight other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – In the expanding matrix of disease-modifying therapeutic options for multiple sclerosis, some "old companions" among the parenteral agents are likely headed by the wayside, Dr. Patricia K. Coyle predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Her plenary address, which highlighted parenteral agents now in the developmental pipeline, also touched on what’s likely to become of the current parenterals.

Here’s her expert analysis:

Interferon-betas and glatiramer acetate: These old standbys are Food and Drug Administration–approved for relapsing forms of MS and for clinically isolated syndrome. Their advantages: they’re fairly well tolerated and their safety profile, thoroughly established over the past 2 decades, holds absolutely no surprises. The big downside is that they are needle-injectable agents.

"I don’t think the market for interferon-betas and glatiramer acetate (Copaxone) is going to disappear, but I think it’s going to slowly shrink because now we have oral options. The biggest impact is going to be on treatment-naive, newly diagnosed patients. People are going to opt for an oral agent rather than an injectable," predicted Dr. Coyle, professor of neurology, vice chair for clinical affairs, and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) Medical Center.

"Also, it’s beginning to become a very crowded market among the interferon-betas. It’s likely you’re going to see one interferon-beta emerge as the dominant option in a shrinking market," she continued.

Natalizumab (Tysabri): This highly effective agent has been dogged by its associated risk of progressive multifocal leukoencephalopathy (PML), but could actually see increased use over the next several years as a consequence of emerging risk-stratification methods that identify a subset of MS patients at low PML risk on natalizumab. But once the novel anti-CD20 monoclonal antibodies reach the marketplace (see ocrelizumab and daclizumab, below), the natalizumab era will be over, in Dr. Coyle’s view.

Mitoxantrone: A true induction agent with sustained efficacy lasting after treatment is stopped. This drug is FDA-approved for all forms of MS except for primary progressive MS. But the associated cardiotoxicity and leukemia risks dictate lifetime monitoring for a drug that can only be given 10 or 11 times. That’s a deal breaker.

"As far as I can tell, mitoxantrone is not being used for MS at all in the U.S. any longer," according to the neurologist.

Rituximab (Rituxan): This IgG1-anti-CD20 chimeric monoclonal antibody rapidly depletes B cells for 4-12 months. Eventually, naive B cells return preferentially over memory B cells. Rituximab is already marketed for non-Hodgkin lymphoma and refractory rheumatoid arthritis. Its manufacturer doesn’t intend to seek an indication for MS; however, earlier highly promising phase II MS studies (N. Engl. J. Med. 2008;358:676-88; Ann. Neurol. 2009;66:460-71) have spurred intensive development of novel anti-CD20 monoclonal antibodies targeting this disease.

Off label, some neurologists are using 1,000 mg of rituximab intravenously followed 15 days later by 500 mg, with dosing repeated every 6 months, she said.

Turning to the parenteral agents of the future, Dr. Coyle said the first up is likely to be:

Alemtuzumab: This agent, which knocks out T cells, is now under FDA review for possible marketing approval based upon impressive phase III results.

Alemtuzumab is a true induction agent. It is given on 8 days over the course of 2 years, and never again. The effects appear to last for several years after the last dose. It is not, however, a cure for MS, Dr. Coyle stressed.

Pegylated interferon beta-1a: The first-year results of the ongoing 2-year phase III ADVANCE trial showed self-administered subcutaneous dosing every 2 weeks to be more effective than every 4 weeks. Will this become the dominant interferon-beta in the marketplace? Way too early to tell, in Dr. Coyle’s view. She also noted the possibility that generic interferon-betas may become available in the United States.

Glatiramer acetate 40 mg: This drug is given subcutaneously three times per week, rather than daily as with the familiar 20-mg formulation. In the GALA (Glatiramer Acetate Low Frequency Administration Study) trial, glatiramer acetate 40 mg had an annualized relapse rate 34% lower than placebo, as well as a 34% reduction in new or relapsing T2 lesions on brain MRI.

Ocrelizumab: The furthest along in development of the novel anti-CD20 agents, this humanized monoclonal antibody is currently in three phase III clinical trials: two for relapsing MS and another for primary progressive MS.

In a phase II study, various doses of ocrelizumab showed 73%-80% reductions in relapses and 89%-96% suppression of MRI contrast lesions.

"The data with ocrelizumab looks great. I think, personally, it could potentially replace natalizumab, depending upon the safety," Dr. Coyle said.

Development of ocrelizumab as a treatment for rheumatoid arthritis and lupus was discontinued because of concerns about an increase in opportunistic infections.

"We’ve not really seen that in the MS cohort so far. It’s a slight background concern. So far, ocrelizumab seems pretty safe," according to the neurologist.

Daclizumab (Zenapax): This subcutaneously administered agent is a humanized IgG1 monoclonal antibody against CD25 and is already on the market for the prevention of organ transplant rejection. It is in the ongoing DECIDE study, a phase III MS clinical trial with intramuscular interferon beta-1a as the comparator. Earlier studies raised some concerns regarding safety and tolerability.

A particularly interesting feature of daclizumab is that it appears to have a biomarker predictive of efficacy: an increase in CD56 bright natural killer cells. Biomarkers of efficacy are desperately needed for MS therapies.

Miscellaneous parenterals: These include other anti-CD20 monoclonal antibodies, among them ofatumumab (Arzerra), already marketed for treatment of refractory chronic lymphocytic leukemia; secukinumab, an anti-interleukin-17 monoclonal antibody that showed efficacy in terms of MRI lesions in a small study; an anti-LINGO-1 monoclonal antibody aimed at stimulating myelin repair; and stem cell therapies that are early in development.

Dr. Coyle predicted more efficacy biomarkers are coming, and noted that neuroprotection and CNS restoration are areas wide open for drug development. Her final prediction regarding parenteral therapies for MS: "A high-efficacy monoclonal antibody, if it’s safe and convenient, could seize the market. The safety will be the critical issue."

She reported having received honoraria from Acorda, Accordant, Bayer, Biogen Idec, EMD Serono, Genzyme/Sanofi Aventis, Novartis, Roche, and Tera.

bjancin@frontlinemedcom.com

ORLANDO – In the expanding matrix of disease-modifying therapeutic options for multiple sclerosis, some "old companions" among the parenteral agents are likely headed by the wayside, Dr. Patricia K. Coyle predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Her plenary address, which highlighted parenteral agents now in the developmental pipeline, also touched on what’s likely to become of the current parenterals.

Here’s her expert analysis:

Interferon-betas and glatiramer acetate: These old standbys are Food and Drug Administration–approved for relapsing forms of MS and for clinically isolated syndrome. Their advantages: they’re fairly well tolerated and their safety profile, thoroughly established over the past 2 decades, holds absolutely no surprises. The big downside is that they are needle-injectable agents.

"I don’t think the market for interferon-betas and glatiramer acetate (Copaxone) is going to disappear, but I think it’s going to slowly shrink because now we have oral options. The biggest impact is going to be on treatment-naive, newly diagnosed patients. People are going to opt for an oral agent rather than an injectable," predicted Dr. Coyle, professor of neurology, vice chair for clinical affairs, and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) Medical Center.

"Also, it’s beginning to become a very crowded market among the interferon-betas. It’s likely you’re going to see one interferon-beta emerge as the dominant option in a shrinking market," she continued.

Natalizumab (Tysabri): This highly effective agent has been dogged by its associated risk of progressive multifocal leukoencephalopathy (PML), but could actually see increased use over the next several years as a consequence of emerging risk-stratification methods that identify a subset of MS patients at low PML risk on natalizumab. But once the novel anti-CD20 monoclonal antibodies reach the marketplace (see ocrelizumab and daclizumab, below), the natalizumab era will be over, in Dr. Coyle’s view.

Mitoxantrone: A true induction agent with sustained efficacy lasting after treatment is stopped. This drug is FDA-approved for all forms of MS except for primary progressive MS. But the associated cardiotoxicity and leukemia risks dictate lifetime monitoring for a drug that can only be given 10 or 11 times. That’s a deal breaker.

"As far as I can tell, mitoxantrone is not being used for MS at all in the U.S. any longer," according to the neurologist.

Rituximab (Rituxan): This IgG1-anti-CD20 chimeric monoclonal antibody rapidly depletes B cells for 4-12 months. Eventually, naive B cells return preferentially over memory B cells. Rituximab is already marketed for non-Hodgkin lymphoma and refractory rheumatoid arthritis. Its manufacturer doesn’t intend to seek an indication for MS; however, earlier highly promising phase II MS studies (N. Engl. J. Med. 2008;358:676-88; Ann. Neurol. 2009;66:460-71) have spurred intensive development of novel anti-CD20 monoclonal antibodies targeting this disease.

Off label, some neurologists are using 1,000 mg of rituximab intravenously followed 15 days later by 500 mg, with dosing repeated every 6 months, she said.

Turning to the parenteral agents of the future, Dr. Coyle said the first up is likely to be:

Alemtuzumab: This agent, which knocks out T cells, is now under FDA review for possible marketing approval based upon impressive phase III results.

Alemtuzumab is a true induction agent. It is given on 8 days over the course of 2 years, and never again. The effects appear to last for several years after the last dose. It is not, however, a cure for MS, Dr. Coyle stressed.

Pegylated interferon beta-1a: The first-year results of the ongoing 2-year phase III ADVANCE trial showed self-administered subcutaneous dosing every 2 weeks to be more effective than every 4 weeks. Will this become the dominant interferon-beta in the marketplace? Way too early to tell, in Dr. Coyle’s view. She also noted the possibility that generic interferon-betas may become available in the United States.

Glatiramer acetate 40 mg: This drug is given subcutaneously three times per week, rather than daily as with the familiar 20-mg formulation. In the GALA (Glatiramer Acetate Low Frequency Administration Study) trial, glatiramer acetate 40 mg had an annualized relapse rate 34% lower than placebo, as well as a 34% reduction in new or relapsing T2 lesions on brain MRI.

Ocrelizumab: The furthest along in development of the novel anti-CD20 agents, this humanized monoclonal antibody is currently in three phase III clinical trials: two for relapsing MS and another for primary progressive MS.

In a phase II study, various doses of ocrelizumab showed 73%-80% reductions in relapses and 89%-96% suppression of MRI contrast lesions.

"The data with ocrelizumab looks great. I think, personally, it could potentially replace natalizumab, depending upon the safety," Dr. Coyle said.

Development of ocrelizumab as a treatment for rheumatoid arthritis and lupus was discontinued because of concerns about an increase in opportunistic infections.

"We’ve not really seen that in the MS cohort so far. It’s a slight background concern. So far, ocrelizumab seems pretty safe," according to the neurologist.

Daclizumab (Zenapax): This subcutaneously administered agent is a humanized IgG1 monoclonal antibody against CD25 and is already on the market for the prevention of organ transplant rejection. It is in the ongoing DECIDE study, a phase III MS clinical trial with intramuscular interferon beta-1a as the comparator. Earlier studies raised some concerns regarding safety and tolerability.

A particularly interesting feature of daclizumab is that it appears to have a biomarker predictive of efficacy: an increase in CD56 bright natural killer cells. Biomarkers of efficacy are desperately needed for MS therapies.

Miscellaneous parenterals: These include other anti-CD20 monoclonal antibodies, among them ofatumumab (Arzerra), already marketed for treatment of refractory chronic lymphocytic leukemia; secukinumab, an anti-interleukin-17 monoclonal antibody that showed efficacy in terms of MRI lesions in a small study; an anti-LINGO-1 monoclonal antibody aimed at stimulating myelin repair; and stem cell therapies that are early in development.

Dr. Coyle predicted more efficacy biomarkers are coming, and noted that neuroprotection and CNS restoration are areas wide open for drug development. Her final prediction regarding parenteral therapies for MS: "A high-efficacy monoclonal antibody, if it’s safe and convenient, could seize the market. The safety will be the critical issue."

She reported having received honoraria from Acorda, Accordant, Bayer, Biogen Idec, EMD Serono, Genzyme/Sanofi Aventis, Novartis, Roche, and Tera.

bjancin@frontlinemedcom.com

ORLANDO – In the expanding matrix of disease-modifying therapeutic options for multiple sclerosis, some "old companions" among the parenteral agents are likely headed by the wayside, Dr. Patricia K. Coyle predicted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Her plenary address, which highlighted parenteral agents now in the developmental pipeline, also touched on what’s likely to become of the current parenterals.

Here’s her expert analysis:

Interferon-betas and glatiramer acetate: These old standbys are Food and Drug Administration–approved for relapsing forms of MS and for clinically isolated syndrome. Their advantages: they’re fairly well tolerated and their safety profile, thoroughly established over the past 2 decades, holds absolutely no surprises. The big downside is that they are needle-injectable agents.

"I don’t think the market for interferon-betas and glatiramer acetate (Copaxone) is going to disappear, but I think it’s going to slowly shrink because now we have oral options. The biggest impact is going to be on treatment-naive, newly diagnosed patients. People are going to opt for an oral agent rather than an injectable," predicted Dr. Coyle, professor of neurology, vice chair for clinical affairs, and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) Medical Center.

"Also, it’s beginning to become a very crowded market among the interferon-betas. It’s likely you’re going to see one interferon-beta emerge as the dominant option in a shrinking market," she continued.

Natalizumab (Tysabri): This highly effective agent has been dogged by its associated risk of progressive multifocal leukoencephalopathy (PML), but could actually see increased use over the next several years as a consequence of emerging risk-stratification methods that identify a subset of MS patients at low PML risk on natalizumab. But once the novel anti-CD20 monoclonal antibodies reach the marketplace (see ocrelizumab and daclizumab, below), the natalizumab era will be over, in Dr. Coyle’s view.

Mitoxantrone: A true induction agent with sustained efficacy lasting after treatment is stopped. This drug is FDA-approved for all forms of MS except for primary progressive MS. But the associated cardiotoxicity and leukemia risks dictate lifetime monitoring for a drug that can only be given 10 or 11 times. That’s a deal breaker.

"As far as I can tell, mitoxantrone is not being used for MS at all in the U.S. any longer," according to the neurologist.

Rituximab (Rituxan): This IgG1-anti-CD20 chimeric monoclonal antibody rapidly depletes B cells for 4-12 months. Eventually, naive B cells return preferentially over memory B cells. Rituximab is already marketed for non-Hodgkin lymphoma and refractory rheumatoid arthritis. Its manufacturer doesn’t intend to seek an indication for MS; however, earlier highly promising phase II MS studies (N. Engl. J. Med. 2008;358:676-88; Ann. Neurol. 2009;66:460-71) have spurred intensive development of novel anti-CD20 monoclonal antibodies targeting this disease.

Off label, some neurologists are using 1,000 mg of rituximab intravenously followed 15 days later by 500 mg, with dosing repeated every 6 months, she said.

Turning to the parenteral agents of the future, Dr. Coyle said the first up is likely to be:

Alemtuzumab: This agent, which knocks out T cells, is now under FDA review for possible marketing approval based upon impressive phase III results.

Alemtuzumab is a true induction agent. It is given on 8 days over the course of 2 years, and never again. The effects appear to last for several years after the last dose. It is not, however, a cure for MS, Dr. Coyle stressed.

Pegylated interferon beta-1a: The first-year results of the ongoing 2-year phase III ADVANCE trial showed self-administered subcutaneous dosing every 2 weeks to be more effective than every 4 weeks. Will this become the dominant interferon-beta in the marketplace? Way too early to tell, in Dr. Coyle’s view. She also noted the possibility that generic interferon-betas may become available in the United States.

Glatiramer acetate 40 mg: This drug is given subcutaneously three times per week, rather than daily as with the familiar 20-mg formulation. In the GALA (Glatiramer Acetate Low Frequency Administration Study) trial, glatiramer acetate 40 mg had an annualized relapse rate 34% lower than placebo, as well as a 34% reduction in new or relapsing T2 lesions on brain MRI.

Ocrelizumab: The furthest along in development of the novel anti-CD20 agents, this humanized monoclonal antibody is currently in three phase III clinical trials: two for relapsing MS and another for primary progressive MS.

In a phase II study, various doses of ocrelizumab showed 73%-80% reductions in relapses and 89%-96% suppression of MRI contrast lesions.

"The data with ocrelizumab looks great. I think, personally, it could potentially replace natalizumab, depending upon the safety," Dr. Coyle said.

Development of ocrelizumab as a treatment for rheumatoid arthritis and lupus was discontinued because of concerns about an increase in opportunistic infections.

"We’ve not really seen that in the MS cohort so far. It’s a slight background concern. So far, ocrelizumab seems pretty safe," according to the neurologist.

Daclizumab (Zenapax): This subcutaneously administered agent is a humanized IgG1 monoclonal antibody against CD25 and is already on the market for the prevention of organ transplant rejection. It is in the ongoing DECIDE study, a phase III MS clinical trial with intramuscular interferon beta-1a as the comparator. Earlier studies raised some concerns regarding safety and tolerability.

A particularly interesting feature of daclizumab is that it appears to have a biomarker predictive of efficacy: an increase in CD56 bright natural killer cells. Biomarkers of efficacy are desperately needed for MS therapies.

Miscellaneous parenterals: These include other anti-CD20 monoclonal antibodies, among them ofatumumab (Arzerra), already marketed for treatment of refractory chronic lymphocytic leukemia; secukinumab, an anti-interleukin-17 monoclonal antibody that showed efficacy in terms of MRI lesions in a small study; an anti-LINGO-1 monoclonal antibody aimed at stimulating myelin repair; and stem cell therapies that are early in development.

Dr. Coyle predicted more efficacy biomarkers are coming, and noted that neuroprotection and CNS restoration are areas wide open for drug development. Her final prediction regarding parenteral therapies for MS: "A high-efficacy monoclonal antibody, if it’s safe and convenient, could seize the market. The safety will be the critical issue."

She reported having received honoraria from Acorda, Accordant, Bayer, Biogen Idec, EMD Serono, Genzyme/Sanofi Aventis, Novartis, Roche, and Tera.

bjancin@frontlinemedcom.com

ORLANDO – Alemtuzumab is far more effective than is high-dose interferon beta-1a in treating patients with highly active relapsing-remitting multiple sclerosis despite prior therapy, according to a new subgroup analysis of the CARE-MS II trial.

Twenty-four percent of alemtuzumab-treated patients in the subgroup with highly-active disease at baseline remained entirely free of demonstrable MS disease activity – both clinically and by MRI – throughout the 2-year randomized trial. In contrast, none of the patients on subcutaneous interferon beta-1a (Rebif) achieved that high standard, Dr. Stephen Krieger reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s an unusual result to see in any of our trials and in any subgroups: zero percent of patients achieving an efficacy goal with one of our approved and highly efficacious agents. I think this demonstrates the high disease activity of these patients, the efficacy gradient between alemtuzumab and interferon, and it also highlights the unmet need for patients with highly-active disease," said Dr. Krieger of Mount Sinai Medical Center, New York.

The CARE-MS II subanalysis also strongly suggests alemtuzumab may provide an important new treatment option for this group of severely affected patients, he added.

Alemtuzumab is a humanized monoclonal antibody to CD52, a protein present on the surface of mature lymphocytes but not on the stem cells from which they originate. Alemtuzumab is approved as Campath for treatment of B-cell chronic lymphocytic leukemia. Genzyme has applied to the Food and Drug Administration and European regulators for a new indication under the trade name Lemtrada for treatment of MS.

CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) was a 2-year, rater-blinded, multicenter, international, phase III clinical trial in which 667 patients with relapsing-remitting MS who had experienced two or more relapses despite treatment during the 2 years immediately prior to enrollment. Participants were randomized 2:1 to alemtuzumab or interferon beta-1a. Alemtuzumab at 12 mg was administered intravenously on 5 consecutive days at the start of the study and again on 3 consecutive days at the 1-year mark, for a total of just 8 doses in 2 years. In contrast, subcutaneous interferon beta-1a at 44 mcg was given three times weekly throughout the study.

The overall results, now published (Lancet 2012;380:1829-39), showed the alemtuzumab group had reductions of 49% in the risk of relapse and 42% in the risk of sustained accumulation of disability, compared with the interferon group.

Dr. Krieger presented a new analysis restricted to the 145 CARE-MS II participants with the most highly active disease as defined by two or more relapses in the year prior to randomization as well as the presence of at least one gadolinium-enhancing lesion on baseline MRI.

"Basically, we’re taking the most active patients from the trial of the more active patients who had already experienced disease activity despite prior therapy," the neurologist explained.

The annualized relapse rate in these patients with highly active disease was 0.33 events with alemtuzumab and .65 events with interferon, for a 51% reduction in favor of the investigational agent. Sixty-four percent of the alemtuzumab group and 36% on interferon remained relapse free during the 2-year study.

Freedom from clinical disease activity was defined as being relapse free as well as free of sustained accumulation of disability, meaning an absence of at least a 1-point increase over baseline on the Expanded Disability Status Scale lasting for at least 6 months. Clinical disease activity–free status for the full 2 years of follow-up was attained by 61% of the alemtuzumab group, compared with 33% of patients on interferon. The adjusted odds ratio was 3.18, meaning patients with highly active disease were more than three times more likely to remain free of clinical disease activity throughout the study if they were on alemtuzumab rather than interferon.

Turning to the serial MRI results, Dr. Krieger noted that 40% of the alemtuzumab group remained free of disease activity by MRI, meaning no new gadolinium-enhancing lesions and no new or enlarging T2 lesions. Only 7.5% of patients with highly active disease assigned to interferon therapy remained free of MRI evidence of disease activity during the 2-year study. Patients on alemtuzumab were an adjusted ninefold more likely to be free of MRI activity than were those on interferon.

The post hoc composite endpoint of freedom from demonstrable MS disease activity required 2 years of freedom from relapse, freedom from MRI activity, and freedom from sustained accumulation of disability. This was the outcome achieved by 24% of patients on alemtuzumab and 0% of those on interferon.

The safety data in the subgroup with highly active disease reflected the findings in the overall CARE-MS II population. Infections occurred in 84% of highly active patients on alemtuzumab and 64% on interferon. Thyroid disorders occurred in 15.5% on alemtuzumab, compared with 2.4% on interferon. Adverse events leading to study discontinuation were seen in 1% on alemtuzumab, compared with 2.4% on interferon.

CARE-MS II was sponsored by Genzyme. Dr. Krieger is a consultant to Genzyme and half a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – Alemtuzumab is far more effective than is high-dose interferon beta-1a in treating patients with highly active relapsing-remitting multiple sclerosis despite prior therapy, according to a new subgroup analysis of the CARE-MS II trial.

Twenty-four percent of alemtuzumab-treated patients in the subgroup with highly-active disease at baseline remained entirely free of demonstrable MS disease activity – both clinically and by MRI – throughout the 2-year randomized trial. In contrast, none of the patients on subcutaneous interferon beta-1a (Rebif) achieved that high standard, Dr. Stephen Krieger reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s an unusual result to see in any of our trials and in any subgroups: zero percent of patients achieving an efficacy goal with one of our approved and highly efficacious agents. I think this demonstrates the high disease activity of these patients, the efficacy gradient between alemtuzumab and interferon, and it also highlights the unmet need for patients with highly-active disease," said Dr. Krieger of Mount Sinai Medical Center, New York.

The CARE-MS II subanalysis also strongly suggests alemtuzumab may provide an important new treatment option for this group of severely affected patients, he added.

Alemtuzumab is a humanized monoclonal antibody to CD52, a protein present on the surface of mature lymphocytes but not on the stem cells from which they originate. Alemtuzumab is approved as Campath for treatment of B-cell chronic lymphocytic leukemia. Genzyme has applied to the Food and Drug Administration and European regulators for a new indication under the trade name Lemtrada for treatment of MS.

CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) was a 2-year, rater-blinded, multicenter, international, phase III clinical trial in which 667 patients with relapsing-remitting MS who had experienced two or more relapses despite treatment during the 2 years immediately prior to enrollment. Participants were randomized 2:1 to alemtuzumab or interferon beta-1a. Alemtuzumab at 12 mg was administered intravenously on 5 consecutive days at the start of the study and again on 3 consecutive days at the 1-year mark, for a total of just 8 doses in 2 years. In contrast, subcutaneous interferon beta-1a at 44 mcg was given three times weekly throughout the study.

The overall results, now published (Lancet 2012;380:1829-39), showed the alemtuzumab group had reductions of 49% in the risk of relapse and 42% in the risk of sustained accumulation of disability, compared with the interferon group.

Dr. Krieger presented a new analysis restricted to the 145 CARE-MS II participants with the most highly active disease as defined by two or more relapses in the year prior to randomization as well as the presence of at least one gadolinium-enhancing lesion on baseline MRI.

"Basically, we’re taking the most active patients from the trial of the more active patients who had already experienced disease activity despite prior therapy," the neurologist explained.

The annualized relapse rate in these patients with highly active disease was 0.33 events with alemtuzumab and .65 events with interferon, for a 51% reduction in favor of the investigational agent. Sixty-four percent of the alemtuzumab group and 36% on interferon remained relapse free during the 2-year study.

Freedom from clinical disease activity was defined as being relapse free as well as free of sustained accumulation of disability, meaning an absence of at least a 1-point increase over baseline on the Expanded Disability Status Scale lasting for at least 6 months. Clinical disease activity–free status for the full 2 years of follow-up was attained by 61% of the alemtuzumab group, compared with 33% of patients on interferon. The adjusted odds ratio was 3.18, meaning patients with highly active disease were more than three times more likely to remain free of clinical disease activity throughout the study if they were on alemtuzumab rather than interferon.

Turning to the serial MRI results, Dr. Krieger noted that 40% of the alemtuzumab group remained free of disease activity by MRI, meaning no new gadolinium-enhancing lesions and no new or enlarging T2 lesions. Only 7.5% of patients with highly active disease assigned to interferon therapy remained free of MRI evidence of disease activity during the 2-year study. Patients on alemtuzumab were an adjusted ninefold more likely to be free of MRI activity than were those on interferon.

The post hoc composite endpoint of freedom from demonstrable MS disease activity required 2 years of freedom from relapse, freedom from MRI activity, and freedom from sustained accumulation of disability. This was the outcome achieved by 24% of patients on alemtuzumab and 0% of those on interferon.

The safety data in the subgroup with highly active disease reflected the findings in the overall CARE-MS II population. Infections occurred in 84% of highly active patients on alemtuzumab and 64% on interferon. Thyroid disorders occurred in 15.5% on alemtuzumab, compared with 2.4% on interferon. Adverse events leading to study discontinuation were seen in 1% on alemtuzumab, compared with 2.4% on interferon.

CARE-MS II was sponsored by Genzyme. Dr. Krieger is a consultant to Genzyme and half a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – Alemtuzumab is far more effective than is high-dose interferon beta-1a in treating patients with highly active relapsing-remitting multiple sclerosis despite prior therapy, according to a new subgroup analysis of the CARE-MS II trial.

Twenty-four percent of alemtuzumab-treated patients in the subgroup with highly-active disease at baseline remained entirely free of demonstrable MS disease activity – both clinically and by MRI – throughout the 2-year randomized trial. In contrast, none of the patients on subcutaneous interferon beta-1a (Rebif) achieved that high standard, Dr. Stephen Krieger reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s an unusual result to see in any of our trials and in any subgroups: zero percent of patients achieving an efficacy goal with one of our approved and highly efficacious agents. I think this demonstrates the high disease activity of these patients, the efficacy gradient between alemtuzumab and interferon, and it also highlights the unmet need for patients with highly-active disease," said Dr. Krieger of Mount Sinai Medical Center, New York.

The CARE-MS II subanalysis also strongly suggests alemtuzumab may provide an important new treatment option for this group of severely affected patients, he added.

Alemtuzumab is a humanized monoclonal antibody to CD52, a protein present on the surface of mature lymphocytes but not on the stem cells from which they originate. Alemtuzumab is approved as Campath for treatment of B-cell chronic lymphocytic leukemia. Genzyme has applied to the Food and Drug Administration and European regulators for a new indication under the trade name Lemtrada for treatment of MS.

CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) was a 2-year, rater-blinded, multicenter, international, phase III clinical trial in which 667 patients with relapsing-remitting MS who had experienced two or more relapses despite treatment during the 2 years immediately prior to enrollment. Participants were randomized 2:1 to alemtuzumab or interferon beta-1a. Alemtuzumab at 12 mg was administered intravenously on 5 consecutive days at the start of the study and again on 3 consecutive days at the 1-year mark, for a total of just 8 doses in 2 years. In contrast, subcutaneous interferon beta-1a at 44 mcg was given three times weekly throughout the study.

The overall results, now published (Lancet 2012;380:1829-39), showed the alemtuzumab group had reductions of 49% in the risk of relapse and 42% in the risk of sustained accumulation of disability, compared with the interferon group.

Dr. Krieger presented a new analysis restricted to the 145 CARE-MS II participants with the most highly active disease as defined by two or more relapses in the year prior to randomization as well as the presence of at least one gadolinium-enhancing lesion on baseline MRI.

"Basically, we’re taking the most active patients from the trial of the more active patients who had already experienced disease activity despite prior therapy," the neurologist explained.

The annualized relapse rate in these patients with highly active disease was 0.33 events with alemtuzumab and .65 events with interferon, for a 51% reduction in favor of the investigational agent. Sixty-four percent of the alemtuzumab group and 36% on interferon remained relapse free during the 2-year study.

Freedom from clinical disease activity was defined as being relapse free as well as free of sustained accumulation of disability, meaning an absence of at least a 1-point increase over baseline on the Expanded Disability Status Scale lasting for at least 6 months. Clinical disease activity–free status for the full 2 years of follow-up was attained by 61% of the alemtuzumab group, compared with 33% of patients on interferon. The adjusted odds ratio was 3.18, meaning patients with highly active disease were more than three times more likely to remain free of clinical disease activity throughout the study if they were on alemtuzumab rather than interferon.

Turning to the serial MRI results, Dr. Krieger noted that 40% of the alemtuzumab group remained free of disease activity by MRI, meaning no new gadolinium-enhancing lesions and no new or enlarging T2 lesions. Only 7.5% of patients with highly active disease assigned to interferon therapy remained free of MRI evidence of disease activity during the 2-year study. Patients on alemtuzumab were an adjusted ninefold more likely to be free of MRI activity than were those on interferon.

The post hoc composite endpoint of freedom from demonstrable MS disease activity required 2 years of freedom from relapse, freedom from MRI activity, and freedom from sustained accumulation of disability. This was the outcome achieved by 24% of patients on alemtuzumab and 0% of those on interferon.

The safety data in the subgroup with highly active disease reflected the findings in the overall CARE-MS II population. Infections occurred in 84% of highly active patients on alemtuzumab and 64% on interferon. Thyroid disorders occurred in 15.5% on alemtuzumab, compared with 2.4% on interferon. Adverse events leading to study discontinuation were seen in 1% on alemtuzumab, compared with 2.4% on interferon.

CARE-MS II was sponsored by Genzyme. Dr. Krieger is a consultant to Genzyme and half a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

ORLANDO – Patients who had multiple sclerosis for a long time or frequently used the Internet were not as accepting of a pilot telecare program as were newer MS patients who didn’t use computers often, according to a small study.

The difference is partly due to the greater body of knowledge that patients with a longer history of MS have gained over the years, sometimes through going online frequently, said Eunme Cha, an epidemiologist at Johns Hopkins University, Baltimore. She presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Naseem S. Miller/IMNG Medical Media

Participants reported that the program had benefits, such as helping them to keep a daily diary of their symptoms and to communicate with their physicians and nurses.

Ms. Cha and her colleagues at the Washington DC VA Medical Center recruited 20 veterans in Washington to use the Home Automated Telemanagement (HAT) system, an online tool they could access via their home computers.

"I wouldn’t say that this is going to replace the entire doctor visit," Ms. Cha said. "But they come pretty far to see the doctor. Traffic is pretty bad in D.C. Some patients travel an entire day to get to their doctor appointment, so they really liked the fact that they could get things done at home."

Mult. Scler.2012;18:472-80A few studies have shown that telemedicine programs can be helpful in the care management of patients with MS. For instance, a 2012 study of 40 patients found that "telecare is a powerful tool for monitoring MS patients at home, carries the potential to improve health care while reducing costs, and should be considered for implementation as part of the management of chronic neurological diseases" (Mult. Scler. 2012;18:472-80).

"I think telemedicine is going to grow in every field of neurology and in every field of medicine that you don’t have to have a hands-on procedure," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC). He was not involved in the study.

But there are challenges to overcome. For example, physicians need to be licensed in every state where they are going to be using telemedicine, Dr. Lisak said in an interview. "But if the politics and the economics can be solved, this is very helpful for people and hospitals that are underserved by subspecialists, and even specialists."

For the pilot study, the research staff visited the patients’ homes, provided them with a link to the MS HAT program, and trained them on the system. 

"We asked the patients to log in every day and enter "my diary" so that they can report their symptoms on a daily basis," said Ms. Cha. "And then physicians and nurses can log in to the clinician site and see what the patient has put in. Also, patients can put in questions to doctors and nurses. So we try to facilitate communication between patients and physicians."

The 20 veterans (mean age, 54 years) included 14 men and 12 African Americans. They had MS for a mean of 15 years. Sixteen patients said they used a computer at home, and the same number reported using the Internet daily. The patients had a mean Expanded Disability Scale Score (EDSS) of 5.3. Their MS subtypes included secondary progressive (11 patients), relapsing-remitting (6), and primary progressive (3). 

A linear regression analysis showed that the length of time patients had MS, how often patients used a computer at home, and English proficiency were all significant predictors of how well the patients accepted the MS HAT program. Meanwhile, race, age, and years of education had no significant relationship with acceptance of the telecare program.

Patients also reported back the benefits of the program, their concerns, and their suggestions. Some said that they liked the ability to report their symptoms right away, keep track of their symptoms, and refresh their memory. They reported concerns with the length of the daily questionnaire and sometimes the redundancy of the content. 

Ms. Cha and her colleagues said that "tailoring this technology to patient needs and preferences may improve its acceptance by veterans in MS."

The team is now looking into conducting a clinical trial, comparing a traditional patient group with those who use the telemedicine program, to see if there are any differences in clinical outcomes and patients’ disease management. 

Ms. Cha had no disclosures. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com
On Twitter @NaseemSMiller

ORLANDO – Patients who had multiple sclerosis for a long time or frequently used the Internet were not as accepting of a pilot telecare program as were newer MS patients who didn’t use computers often, according to a small study.

The difference is partly due to the greater body of knowledge that patients with a longer history of MS have gained over the years, sometimes through going online frequently, said Eunme Cha, an epidemiologist at Johns Hopkins University, Baltimore. She presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Naseem S. Miller/IMNG Medical Media

Participants reported that the program had benefits, such as helping them to keep a daily diary of their symptoms and to communicate with their physicians and nurses.

Ms. Cha and her colleagues at the Washington DC VA Medical Center recruited 20 veterans in Washington to use the Home Automated Telemanagement (HAT) system, an online tool they could access via their home computers.

"I wouldn’t say that this is going to replace the entire doctor visit," Ms. Cha said. "But they come pretty far to see the doctor. Traffic is pretty bad in D.C. Some patients travel an entire day to get to their doctor appointment, so they really liked the fact that they could get things done at home."

Mult. Scler.2012;18:472-80A few studies have shown that telemedicine programs can be helpful in the care management of patients with MS. For instance, a 2012 study of 40 patients found that "telecare is a powerful tool for monitoring MS patients at home, carries the potential to improve health care while reducing costs, and should be considered for implementation as part of the management of chronic neurological diseases" (Mult. Scler. 2012;18:472-80).

"I think telemedicine is going to grow in every field of neurology and in every field of medicine that you don’t have to have a hands-on procedure," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC). He was not involved in the study.

But there are challenges to overcome. For example, physicians need to be licensed in every state where they are going to be using telemedicine, Dr. Lisak said in an interview. "But if the politics and the economics can be solved, this is very helpful for people and hospitals that are underserved by subspecialists, and even specialists."

For the pilot study, the research staff visited the patients’ homes, provided them with a link to the MS HAT program, and trained them on the system. 

"We asked the patients to log in every day and enter "my diary" so that they can report their symptoms on a daily basis," said Ms. Cha. "And then physicians and nurses can log in to the clinician site and see what the patient has put in. Also, patients can put in questions to doctors and nurses. So we try to facilitate communication between patients and physicians."

The 20 veterans (mean age, 54 years) included 14 men and 12 African Americans. They had MS for a mean of 15 years. Sixteen patients said they used a computer at home, and the same number reported using the Internet daily. The patients had a mean Expanded Disability Scale Score (EDSS) of 5.3. Their MS subtypes included secondary progressive (11 patients), relapsing-remitting (6), and primary progressive (3). 

A linear regression analysis showed that the length of time patients had MS, how often patients used a computer at home, and English proficiency were all significant predictors of how well the patients accepted the MS HAT program. Meanwhile, race, age, and years of education had no significant relationship with acceptance of the telecare program.

Patients also reported back the benefits of the program, their concerns, and their suggestions. Some said that they liked the ability to report their symptoms right away, keep track of their symptoms, and refresh their memory. They reported concerns with the length of the daily questionnaire and sometimes the redundancy of the content. 

Ms. Cha and her colleagues said that "tailoring this technology to patient needs and preferences may improve its acceptance by veterans in MS."

The team is now looking into conducting a clinical trial, comparing a traditional patient group with those who use the telemedicine program, to see if there are any differences in clinical outcomes and patients’ disease management. 

Ms. Cha had no disclosures. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com
On Twitter @NaseemSMiller

ORLANDO – Patients who had multiple sclerosis for a long time or frequently used the Internet were not as accepting of a pilot telecare program as were newer MS patients who didn’t use computers often, according to a small study.

The difference is partly due to the greater body of knowledge that patients with a longer history of MS have gained over the years, sometimes through going online frequently, said Eunme Cha, an epidemiologist at Johns Hopkins University, Baltimore. She presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Naseem S. Miller/IMNG Medical Media

Participants reported that the program had benefits, such as helping them to keep a daily diary of their symptoms and to communicate with their physicians and nurses.

Ms. Cha and her colleagues at the Washington DC VA Medical Center recruited 20 veterans in Washington to use the Home Automated Telemanagement (HAT) system, an online tool they could access via their home computers.

"I wouldn’t say that this is going to replace the entire doctor visit," Ms. Cha said. "But they come pretty far to see the doctor. Traffic is pretty bad in D.C. Some patients travel an entire day to get to their doctor appointment, so they really liked the fact that they could get things done at home."

Mult. Scler.2012;18:472-80A few studies have shown that telemedicine programs can be helpful in the care management of patients with MS. For instance, a 2012 study of 40 patients found that "telecare is a powerful tool for monitoring MS patients at home, carries the potential to improve health care while reducing costs, and should be considered for implementation as part of the management of chronic neurological diseases" (Mult. Scler. 2012;18:472-80).

"I think telemedicine is going to grow in every field of neurology and in every field of medicine that you don’t have to have a hands-on procedure," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC). He was not involved in the study.

But there are challenges to overcome. For example, physicians need to be licensed in every state where they are going to be using telemedicine, Dr. Lisak said in an interview. "But if the politics and the economics can be solved, this is very helpful for people and hospitals that are underserved by subspecialists, and even specialists."

For the pilot study, the research staff visited the patients’ homes, provided them with a link to the MS HAT program, and trained them on the system. 

"We asked the patients to log in every day and enter "my diary" so that they can report their symptoms on a daily basis," said Ms. Cha. "And then physicians and nurses can log in to the clinician site and see what the patient has put in. Also, patients can put in questions to doctors and nurses. So we try to facilitate communication between patients and physicians."

The 20 veterans (mean age, 54 years) included 14 men and 12 African Americans. They had MS for a mean of 15 years. Sixteen patients said they used a computer at home, and the same number reported using the Internet daily. The patients had a mean Expanded Disability Scale Score (EDSS) of 5.3. Their MS subtypes included secondary progressive (11 patients), relapsing-remitting (6), and primary progressive (3). 

A linear regression analysis showed that the length of time patients had MS, how often patients used a computer at home, and English proficiency were all significant predictors of how well the patients accepted the MS HAT program. Meanwhile, race, age, and years of education had no significant relationship with acceptance of the telecare program.

Patients also reported back the benefits of the program, their concerns, and their suggestions. Some said that they liked the ability to report their symptoms right away, keep track of their symptoms, and refresh their memory. They reported concerns with the length of the daily questionnaire and sometimes the redundancy of the content. 

Ms. Cha and her colleagues said that "tailoring this technology to patient needs and preferences may improve its acceptance by veterans in MS."

The team is now looking into conducting a clinical trial, comparing a traditional patient group with those who use the telemedicine program, to see if there are any differences in clinical outcomes and patients’ disease management. 

Ms. Cha had no disclosures. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com
On Twitter @NaseemSMiller

ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.

In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.

Bruce Jancin/IMNG Medical Media

The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.

The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.

A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.

In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.

The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.

The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.

One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.

Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.

The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.

The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.

bjancin@frontlinemedcom.com

ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.

In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.

Bruce Jancin/IMNG Medical Media

The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.

The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.

A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.

In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.

The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.

The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.

One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.

Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.

The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.

The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.

bjancin@frontlinemedcom.com

ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.

In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.

Bruce Jancin/IMNG Medical Media

The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.

The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.

A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.

In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.

The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.

The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.

One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.

Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.

The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.

The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.

bjancin@frontlinemedcom.com

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

ORLANDO – Sepsis, pulmonary infections, aspiration, and ischemic heart disease accounted for the bulk of excess mortality seen in patients with multiple sclerosis, compared with the matched general population, in a large U.S. study.

"Increased awareness of these potentially fatal conditions for patients with MS can improve patient care by increasing physician vigilance and facilitating early intervention," Dr. Michael J. Corwin said at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Because MS is a chronic, progressive, incurable disease, the death certificates of MS patients often list MS as the underlying cause of death. Accepting that at face value would mean nearly two-thirds of excess mortality seen in the study was because of advanced MS, said Dr. Corwin. But with the use of a novel cause-of-death algorithm, he and his colleagues were able to identify key intermediate and potentially interruptible steps on the pathway from end-stage MS to death.

He presented a retrospective matched cohort study of 30,402 patients with MS and 89,818 matched non-MS comparators, all drawn from a large, national, U.S. commercial health-plan database. The mortality rate was doubled among the MS population: 5.2%, compared with 2.6% in controls. This translated to a death rate of 899 per 100,000 person-years in the MS group and 446 per 100,000 person-years in the control group, reported Dr. Corwin, an associate professor of pediatrics and epidemiology at Boston University’s Schools of Medicine and Public Health.

The study entailed detailed analysis of the death records of 1,579 MS patients and 2,332 matched controls. Because of the notorious lack of uniformity in the way death certificate data are recorded, it can be difficult to determine the immediate cause of death from these records, noted Dr. Corwin. Therefore, he and his coinvestigators developed the algorithm for doing so.

Specifically, the algorithm showed that infection accounted for 21% of the excess mortality in the MS population, cardiovascular disease 13%, and pulmonary disease 10%. Collectively, these three causes of death accounted for 44% of the excess mortality. Another 29% of the excess remained attributable to late-stage MS because of the lack of additional death record data that might have allowed a more specific categorization.

Delving more deeply into the principal causes of death, the investigators determined that sepsis was the No. 1 contributor to the excess mortality seen in the MS population. It accounted for 45 of the 453 excess deaths per 100,000 person-years. Sepsis was followed by pulmonary infection at 41, pulmonary aspiration at 27, and ischemic heart disease at 17.

The prominent role of pulmonary infections in contributing to excess mortality in patients with MS seen in this study confirms a finding from the 21-year follow-up of the landmark, multicenter, interferon beta-1b randomized treatment trial (BMJ Open 2012 Nov 30;2(6). pii: e001972 [doi: 10.1136/bmjopen-2012-001972]). Respiratory diseases were also the top cause of excess mortality found among MS patients in a recent, large, British, national population-based registry (Eur. J. Neurol. 2012;19:1007-14).

Dr. Corwin is a principal in Care-Safe, a consulting firm contracted by Bayer HealthCare Pharmaceuticals to conduct the U.S. study.

bjancin@frontlinemedcom.com

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller