AAN Annual Meeting

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Oral therapies for relapsing-remitting multiple sclerosis that are in the development pipeline have neurologists feeling both excited and a bit apprehensive.

"There are a whole slew of orals coming," Dr. Mariko Kita said in an interview at the annual meeting of the American Academy of Neurology. "It’s really exciting, but I think it will be challenging for the clinician" because there will be inadequate guidance on which drug or drugs to prioritize in treatment, how best to combine various therapies, and other clinical questions.

"I think it’s going to be very intimidating, actually," said Dr. Kita, director of the Multiple Sclerosis Center at Virginia Mason Medical Center, Seattle.

She comoderated a session at the meeting on multiple sclerosis trials that included a report on a pooled analysis of safety data on the only approved oral therapy for multiple sclerosis, fingolimod (Gilenya). The session also included positive phase III clinical trial results for the experimental oral therapy teriflunomide. Earlier in the meeting, separate investigators reported positive phase III clinical trial results for the experimental oral therapy laquinimod.

Another oral agent under study, BG-12 (dimethyl fumarate), received Fast Track designation from the Food and Drug Administration and is in phase III clinical trials. Cladribine (Leustatin), which is currently marketed as chemotherapy for certain leukemias and lymphomas, initially was rejected by the FDA when it was submitted for approval as an oral therapy for multiple sclerosis. Following resubmission by the manufacturer, the FDA in early 2011 sent a letter to the company acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit considerations before it could be approved.

Dr. Kita’s comoderator, Dr. Benjamin N. Greenberg, commented after the session that with the expected approvals of several oral agents for multiple sclerosis over the next few years, "I’m getting concerned that there’s going to be a little bit of a free-for-all coming." But he added, "It’s good to have options. We’re all thrilled."

The only head-to-head comparison of an oral therapy against another active treatment for multiple sclerosis so far is a study of fingolimod vs. interferon, he noted. Direct comparisons of the various oral agents will be needed to help clinicians develop treatment strategies, said Dr. Greenberg, a neurologist at the University of Texas Southwestern Medical Center, Dallas.

Gilenya may have some superior efficacy, compared with once-weekly interferon dosing, Dr. Kita said, but its potential adverse cardiovascular effects and "downstream consequences in terms of effects on different organ systems makes another oral daily alternative with less toxicity that much more appealing."

Dr. Aaron Miller of Mount Sinai School of Medicine, New York, and Dr. Jerry S. Wolinsky of the University of Texas Health Science Center, Houston, presented results of the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial during the session. The multinational, double-blind study randomized 1,088 patients with relapsing-remitting multiple sclerosis to a single daily dose of 7 mg or 14 mg of teriflunomide or placebo for 2 years.

Results of the TEMSO trial were first reported in late 2010.

Both doses reduced the annualized relapse rate by approximately 31%, compared with placebo. The annualized relapse rate was 0.37 in each of the treatment groups and 0.54 in the placebo group. The risk of disability progression also was significantly reduced by 30% in the 14-mg group but was not significantly different in the 7-mg group, compared with placebo.

Both doses showed significant improvements, compared with placebo, in brain disease activity on various MRI tests, although some MRI measures of disease activity were significantly better only in the high-dose group, compared with placebo.

Results of the 2-year, randomized, double-blind study of laquinimod that was presented earlier at the meeting showed an annual relapse rate of 0.304 on laquinimod, a 23% reduction compared with a rate of 0.395 on placebo. The laquinimod group also showed 33% less brain atrophy and significant improvements in brain disease activity on various MRI measures.

Both teriflunomide and laquinimod appeared to be relatively well tolerated. But among 11 women who became pregnant in the TEMSO study, 3 of 4 spontaneous abortions occurred in the teriflunomide groups. Six of the other pregnant women underwent induced abortions, and one woman successfully delivered a healthy baby.

"I thought that the teriflunomide study was interesting. It was impressive to see that a fairly low dose like that, which seems to be very well tolerated, could have effects on both the MRI and on the clinical end points," Dr. Kita said. "My concern for it is making sure that we understand what the impact is on the female population, on the childbearing years. We know that its parent compound can have teratogenic effects, and I’m not sure we know yet how safe teriflunomide will be in the population."

Dr. Kita said she has no relevant conflicts of interest. Dr. Greenberg disclosed financial relationships with DioGenix, Biogen Idec (which is developing BG-12), EMD Serono (which is developing cladribine), Teva Neurosciences (which is developing laquinimod), and the Greater Good Foundation.

Sanofi-Aventis, which is developing teriflunomide, funded the TEMSO trial. Dr. Miller, Dr. Wolinsky, and many of their associates in the study disclosed relationships with Sanofi-Aventis and with numerous other companies that make therapies for multiple sclerosis. Three of their co-investigators were employees of Sanofi-Aventis.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

Among non–North American patients in Central and South America, however, the seizure rate in the placebo group fell by approximately 25%, and the drug treatment effect was not statistically different.

"I tend to believe the North American data, but that has to be confirmed," Dr. French said. She speculated that patient selection influenced the regional differences. "In North America, we have EEG monitoring and can confirm that they have epilepsy before we enroll them in trials," which is less likely to happen in some other areas, she said.

Perampanel is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. Most antiepileptics are channel-acting drugs or work via inhibition, Dr. French noted. "This is the first drug to block the excitatory side," she said.

Dr. Marc Nuwer, professor of neurology at the University of California, Los Angeles, said in an interview that the most exciting thing about perampanel is that it establishes a new category of drugs. "We’re all going to be trying it out" if perampanel gets approved.

Dr. Nuwer did not have a role in the perampanel studies. He said he has no conflicts of interest.

A second phase III trial identical in design to this one is underway to verify the results, Dr. French said. Results are expected to be available in the summer of 2011.

The study’s design was similar to an earlier multinational, randomized, placebo-controlled study of lower doses of perampanel in 712 patients with refractory partial seizures that was reported at the annual meeting of the American Epilepsy Society in 2010. In that study, 19 weeks of adjunctive perampanel therapy significantly reduced the frequency of seizures by 34% in patients randomized to receive a once-daily 8-mg dose and by 29% in patients randomized to a 4-mg dose, compared with a 14% reduction in the placebo group. Patients randomized to a 2-mg dose saw a 16% drop in seizures, which was not significantly different, compared with placebo.

Both studies started with 6 weeks of observation to count the number of seizures, then a 6-week titration phase followed by a 13-week maintenance period. Patients continued taking their regular antiepileptic therapy during the studies and were offered enrollment in open-label extension studies after completion of the trials.

Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

HONOLULU – Two years of taking the investigational oral drug laquinimod reduced multiple sclerosis relapses and slowed progression toward disability and brain atrophy, compared with placebo, in a phase III study of 1,106 patients with relapsing-remitting multiple sclerosis.

The annualized relapse rate declined by 23% among patients who took laquinimod 0.6 mg daily in the randomized trial, which involved 139 centers in 24 countries, Dr. Giancarlo Comi and his associates reported at the annual meeting of the American Academy of Neurology. The annualized relapse rates were 0.304 on laquinimod and 0.395 on placebo.

The laquinimod group also showed a 36% reduction in disability progression, which "is quite a big thing, more than what has been reported" in previous drug studies, said Dr. Comi, director of the department of neurology and the institute of experimental neurology at the Scientific Institute and University of Vita-Salute San Raffaele, Milan.

Most importantly, he said in an interview, the laquinimod group showed 33% less brain atrophy over the course of the study. "That’s interesting because most drugs fail to have an effect on this," he said.

These multiple benefits may be due to laquinimod’s novel mechanism of action, which addresses both the disease’s acute inflammatory activity and the accumulation of irreversible tissue damage, he said.

The results suggest that laquinimod is a "very promising" treatment, Dr. Comi said. "In the end, what matters is how much damage there is to the patient and how much the drug was able to prevent that."

Baseline characteristics of the two groups were similar, including demographics, clinical factors and MRI findings. At the start of the study, 46% of the laquinimod group and 40% of the placebo group had active disease. Patients in both groups had had MS for an average of 9 years.

Patients underwent clinical evaluations every 3 months and yearly MRI exams. By the end of the study, the mean number of gadolinium-enhanced lesions on MRI was 37% lower in the laquinimod group and the mean number of new T2 lesions was 30% lower, compared with placebo. The mean number of new T1 lesions, which are characterized by more severe tissue damage, was 27% lower with the drug, compared with placebo.

Laquinimod appeared to be well tolerated. Seventy-nine percent of patients who were randomized to laquinimod and 77% of patients who were randomized to placebo finished the double-blind study.

Elevations of liver enzymes were more common in the laquinimod group (7%) than in the placebo group (3%), but these were transient and reversible and did not lead to any signs of liver problems, Dr. Comi said. Liver enzyme elevations greater than three times the upper limit of normal occurred in 2% of the placebo group and 5% of the laquinimod group.

The overall rates of adverse events were low (22% on laquinimod and 16% on placebo) and did not differ significantly between the drug and placebo groups. Two patients on placebo died from unrelated causes, with no deaths in the laquinimod group. The laquinimod group reported higher rates of abdominal pain (5%) and back pain (16%), compared with placebo (3% and 9%, respectively).

In 2010, the oral medication fingolimod (Gilenya) was approved as adjunctive therapy for relapsing-remitting MS. Concerns about increased risks for cardiac problems, immune suppression, and cancer with fingolimod were not a problem in the laquinimod study, Dr. Comi said.

One patient in the placebo group developed pericarditis. There was no evidence of decreased immune function on laquinimod. For example, 17% on placebo on 20% on laquinimod developed herpes infection. There were six cases of cancer in the placebo group and eight in the laquinimod group, for rates of 1.1% and 1.5%, respectively.

A parallel trial is underway to confirm the findings, and results from that trial are expected in the fall of 2011, he said.

Teva Pharmaceuticals, which is developing laquinimod, funded the study. Dr. Comi has received compensation from Teva, Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering Pharma. Some of his associates in the study reported relationships with Teva and other companies manufacturing drugs for MS.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.

Results from a randomized trial show that low-intensity treadmill exercise leads to more consistent improvements in the gait and mobility of patients with Parkinson’s disease than does high-intensity treadmill exercise or stretching and resistance exercise.

However, only patients who participated in stretching and resistance exercise experienced significant improvements in the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS).

Photo credit: Sharon Boston, University of Maryland School of Medicine, Baltimore.

"There isn’t a neurologist who cares for patients with Parkinson’s that doesn’t have their patients ask them, ‘What should I do to help myself? What kind of exercise, if any, should I do?’ " Dr. Lisa M. Shulman said in an interview in advance of the annual meeting of the American Academy of Neurology, where the research was presented. "We haven’t had a good answer to that question for years. This study is a good start in terms of telling patients what they can do to help themselves. I’ve begun to tell my patients that they should do a combination of low-intensity treadmill exercise and stretching resistance training to get the range of benefits that we demonstrated in our study."

Dr. Shulman, a professor of neurology at the University of Maryland, Baltimore, and her associates enrolled 67 Parkinson’s patients who had trouble walking into one of three groups: high-intensity treadmill (30 minutes at 70%-80% heart rate reserve); low-intensity treadmill (50 minutes at 40%-50% heart rate reserve); or stretching and resistance exercises (two sets of 10 repetitions of leg presses, extensions, and curls performed on exercise machines). The study participants exercised three times a week for 3 months and were supervised by exercise physiologists at the Baltimore Veterans Affairs Medical Center.

Baseline pre- and posttraining measures included the 6-minute walk; 10-meter and 50-foot gait speeds; peak oxygen consumption; and the UPDRS, which evaluates disease symptoms such as tremor, rigidity, loss of dexterity, slowness, walking, and balance.

The mean age of patients was 66 years and 75% were male. Dr. Shulman reported that at the end of 3 months, all modes of exercise improved distance on the 6-minute walk, with significant improvements in the low-intensity treadmill group and in the stretching/resistance group, and a trend toward significance in the high-intensity treadmill group. The greatest improvement was seen in the low-intensity treadmill group, in which patients walked 11% further over 6 minutes, a distance equivalent to half a city block.

Both treadmill groups significantly improved their 10-meter fast gait, but the low-intensity treadmill group demonstrated greater improvement on the 50-foot fast gait. Both treadmill groups improved peak oxygen consumption.

Only patients in the stretching/resistance group experienced significant improvements in the motor component of the UPDRS, the key measure of Parkinsonian motor symptoms.

"The fact that the low-intensity treadmill group had more consistent benefit in terms of gait and mobility was surprising," Dr. Shulman said. "Our main interest was improvement in gait and mobility, because those are the most disabling symptoms of Parkinson’s disease. A key fact is that it wasn’t necessary to greatly increase the intensity of walking to achieve benefit. That means that more people with a greater range of disability can benefit from exercise in Parkinson’s disease."

The positive impact of stretching and resistance exercise was also surprising, she said. "People with Parkinson’s who have rigidity tend to develop a stooped posture; they tend to lose their range of motion and general mobility because they’re stiff and slow," Dr. Shulman said. "One possibility is that the stretching and strengthening exercises in that group relieved symptoms of loss of range of motion and stiffness over time."

She acknowledged certain limitations of the study, including the fact that outcomes were evaluated only at 90 days and that it was a single-blinded (not a double-blinded) analysis. "There isn’t any way to get around that, since patients in exercise trials are aware of their exercise training," she noted. "It’s ironic that all of our patients were hoping that they would be assigned to the high-intensity treadmill group. They all wanted to be in that group because it was clearly the most strenuous group. When they were assigned to the low-intensity group or to the stretching/resistance group, they were somewhat disappointed, yet those were precisely the groups that were most effective."

The study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the VA Center of Excellence in Exercise and Robotics for Neurological Disorders, and the Baltimore VA Medical Center’s Geriatric Research, Education, and Clinical Center.

Dr. Shulman said that she had no relevant financial conflicts to disclose.