Sherry Boschert

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

LOS ANGELES – A large population-based study found better outcomes a year after childhood arterial ischemic stroke than were reported in previous studies that analyzed hospital-based cohorts.

The prospective Study of Outcome in Childhood Stroke (SOCS) followed cases of arterial ischemic stroke in children older than 27 days and younger than 16 years that were identified by British networks of medical specialists and surveillance databases from July 2008 through June 2009. The data collected cover 6 million children – 63% of children in England.

They found 82 cases of arterial ischemic stroke, for an incidence of 1.4/100,000 children per year, Dr. Andrew A. Mallick reported. Consent for follow-up assessments in the study was not available for seven patients, and six died (though none died primarily of stroke).

The parents of the remaining 69 children completed the International Pediatric Stroke Study Recovery and Recurrence Questionnaire. Their answers suggested that 32 (46%) children had fully recovered from the stroke and that 46 (67%) needed no extra help in daily activities.

Physician assessments using the Pediatric Stroke Outcome Measure suggested that 45% of the children were normal with no stroke-related deficits a year later. In the rest, physicians rated the severity of deficits as mild in 10% of children, moderate in 20%, and severe in 25%, said Dr. Mallick of the University of Bristol (England).

The percentages of children in the SOCS rated as fully recovered by parents and physicians compares favorably with the largest and most-often cited previous studies of outcome after childhood stroke, he said at the meeting, sponsored by the American Heart Association. Those studies reported normal function after arterial ischemic stroke in 32% and 13% of children (J. Child Neurol. 2000;15:316-24; Dev. Med. Child Neurol. 2000;42:455-61).

The previous studies followed patients from tertiary care children’s hospitals in Canada and England. Hospital-based registries generally include patients with more severe strokes who are at a higher risk of complications or death, he said.

The SOCS findings should affect prognosis after childhood arterial ischemic stroke and the design of clinical trials, Dr. Mallick said.

"We’ve seen from our data that almost half the children are prepared to make a full recovery. If some of the proposed therapies are relatively high risk, I think we need to carefully consider whether we want to be giving children who are going to recover anyway such potentially dangerous therapies," he said.

When neurologic deficits were seen in the SOCS, about half were sensorimotor deficits, approximately a quarter were cognition or behavioral deficits, and fewer were deficits in expressive or receptive speech, Dr. Mallick and his associates found.

He said he and his coinvestigators had no relevant financial disclosures. The Stroke Association (United Kingdom) funded the study.

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 meetingo 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 tied 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 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.

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

Source DR. COMI

View on The News

Drug Will Easily Find a Niche

The results were very positive on disease and on relapse rate reduction. These were both very good signs. In addition, laquinimod was a relatively or maybe very safe medication for people to take.

In contrast, some of the newer agents are having difficulty going through the phase III testing for approval. For example, one of the other agents has been held up in the Food and Drug Administration review because of safety concerns.

Another one that was just approved has risks for immune suppression. Laquinimod does not appear to have a risk for immune suppression, yet it has efficacy in relapsing-remitting MS.

Many patients who will tolerate one drug will not tolerate another drug, so it will be very easy to find a niche for this particular drug.

Most patients don't want an injectable therapy. On the other hand, we have to recognize that even an oral medication can pose some risks. Laquinimod does not seem to have any of those risks, but it causes immune modulation, so it may fit in early MS where it may show its greater efficacy.

What we've learned in the last 10 years – and most important of all – is not which drug to use, but when to treat, and to treat early, because treating early seems to be where we can see the best and most effect.

Laquinimod has a different mechanism of action. It seems to involve the signaling pathways that are in the innate immune system. We're learning about that now. There is going to be much more to be learned about this drug after it's approved in terms of its mechanisms of action.

SCOTT S. ZAMVIL, M.D., is professor of neurology at the University of California, San Francisco. He was not associated with the laquinimod study. He has been a consultant for Teva Pharmaceuticals, Biogen Idec, and Serono. In addition, Dr. Zamvil has received grant support or served on data safety monitoring boards for multiple drug companies.

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 meetingo 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 tied 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 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.

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

Source DR. COMI

View on The News

Drug Will Easily Find a Niche

The results were very positive on disease and on relapse rate reduction. These were both very good signs. In addition, laquinimod was a relatively or maybe very safe medication for people to take.

In contrast, some of the newer agents are having difficulty going through the phase III testing for approval. For example, one of the other agents has been held up in the Food and Drug Administration review because of safety concerns.

Another one that was just approved has risks for immune suppression. Laquinimod does not appear to have a risk for immune suppression, yet it has efficacy in relapsing-remitting MS.

Many patients who will tolerate one drug will not tolerate another drug, so it will be very easy to find a niche for this particular drug.

Most patients don't want an injectable therapy. On the other hand, we have to recognize that even an oral medication can pose some risks. Laquinimod does not seem to have any of those risks, but it causes immune modulation, so it may fit in early MS where it may show its greater efficacy.

What we've learned in the last 10 years – and most important of all – is not which drug to use, but when to treat, and to treat early, because treating early seems to be where we can see the best and most effect.

Laquinimod has a different mechanism of action. It seems to involve the signaling pathways that are in the innate immune system. We're learning about that now. There is going to be much more to be learned about this drug after it's approved in terms of its mechanisms of action.

SCOTT S. ZAMVIL, M.D., is professor of neurology at the University of California, San Francisco. He was not associated with the laquinimod study. He has been a consultant for Teva Pharmaceuticals, Biogen Idec, and Serono. In addition, Dr. Zamvil has received grant support or served on data safety monitoring boards for multiple drug companies.

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 meetingo 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 tied 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 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.

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

Source DR. COMI

View on The News

Drug Will Easily Find a Niche

The results were very positive on disease and on relapse rate reduction. These were both very good signs. In addition, laquinimod was a relatively or maybe very safe medication for people to take.

In contrast, some of the newer agents are having difficulty going through the phase III testing for approval. For example, one of the other agents has been held up in the Food and Drug Administration review because of safety concerns.

Another one that was just approved has risks for immune suppression. Laquinimod does not appear to have a risk for immune suppression, yet it has efficacy in relapsing-remitting MS.

Many patients who will tolerate one drug will not tolerate another drug, so it will be very easy to find a niche for this particular drug.

Most patients don't want an injectable therapy. On the other hand, we have to recognize that even an oral medication can pose some risks. Laquinimod does not seem to have any of those risks, but it causes immune modulation, so it may fit in early MS where it may show its greater efficacy.

What we've learned in the last 10 years – and most important of all – is not which drug to use, but when to treat, and to treat early, because treating early seems to be where we can see the best and most effect.

Laquinimod has a different mechanism of action. It seems to involve the signaling pathways that are in the innate immune system. We're learning about that now. There is going to be much more to be learned about this drug after it's approved in terms of its mechanisms of action.

SCOTT S. ZAMVIL, M.D., is professor of neurology at the University of California, San Francisco. He was not associated with the laquinimod study. He has been a consultant for Teva Pharmaceuticals, Biogen Idec, and Serono. In addition, Dr. Zamvil has received grant support or served on data safety monitoring boards for multiple drug companies.

LAS VEGAS – Climate change has expanded geographic ranges of tick and parasite vectors, pushing some infectious diseases that cause joint pain in children into unfamiliar territory, Dr. Sigfrid A. Muller said at a dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Lyme disease has spread well into Canada, and leishmaniasis is moving north from Mexico into Texas, Arizona, Oklahoma, and Ohio. Reports of Chagas disease are increasing in the United States and Central and South America. Peru and Ecuador are seeing more Carrion's disease, said Dr. Muller, a dermatologist in Las Vegas and chair of the International Society of Dermatology's Climate Change Task Force.

Global warming may be debated in the popular media, but there is little controversy about it in the scientific literature, he said. June 2010 was the warmest month on record (combining global land and ocean average surface temperatures) and the 304th consecutive month with a global temperature above the 20th-century average, according to the National Oceanic and Atmospheric Administration.

Scientists predict changes already underway will warm the planet at least 2 or 3 degrees Centigrade this century, and perhaps double or triple that if humans don't alter the behaviors that contribute to climate change. Current scientific estimates suggest that an increase of 2 degrees Centigrade may be the “tipping point” that triggers irreversible changes (such as methane release from melting permafrost) with unpredictable but severe consequences for the planet and its inhabitants, Dr. Muller said.

Some projected changes already are being seen in the extreme summer heat in western Russia, flooding in Pakistan, intense wildfires in Australia, and drought in regions of the United States and elsewhere. The patterns of resulting changes in joint diseases due to infection from these conditions will vary regionally depending on altitude, latitude, storms, deforestation, desertification, urbanization, land use patterns, energy production, and transportation.

Dr. Muller highlighted changes in several diseases:

▸ Lyme disease. Lyme disease used to be limited to five U.S. geographic regions, but its geographic range has expanded into many areas of Canada as temperatures have become more hospitable to the rodents and deer that act as vectors and reservoirs, spreading into southern and northern Ontario, southern Québec, Manitoba, the Prairie Provinces, the Maritime Provinces, and British Columbia.

▸ Carrion's disease. Children bear the brunt of this reemerging disease that has spread to new areas between the jungle and highlands of Peru and Ecuador. Its symptoms take the form of bone pain, among others. Changes in sea surface temperatures that triggered extreme seasonal rain patterns known as El Niño events in the 1980s and 1990s were associated with a nearly fourfold increase in Carrion's disease in Peru's Ancash region.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Climate change has expanded geographic ranges of tick and parasite vectors, pushing some infectious diseases that cause joint pain in children into unfamiliar territory, Dr. Sigfrid A. Muller said at a dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Lyme disease has spread well into Canada, and leishmaniasis is moving north from Mexico into Texas, Arizona, Oklahoma, and Ohio. Reports of Chagas disease are increasing in the United States and Central and South America. Peru and Ecuador are seeing more Carrion's disease, said Dr. Muller, a dermatologist in Las Vegas and chair of the International Society of Dermatology's Climate Change Task Force.

Global warming may be debated in the popular media, but there is little controversy about it in the scientific literature, he said. June 2010 was the warmest month on record (combining global land and ocean average surface temperatures) and the 304th consecutive month with a global temperature above the 20th-century average, according to the National Oceanic and Atmospheric Administration.

Scientists predict changes already underway will warm the planet at least 2 or 3 degrees Centigrade this century, and perhaps double or triple that if humans don't alter the behaviors that contribute to climate change. Current scientific estimates suggest that an increase of 2 degrees Centigrade may be the “tipping point” that triggers irreversible changes (such as methane release from melting permafrost) with unpredictable but severe consequences for the planet and its inhabitants, Dr. Muller said.

Some projected changes already are being seen in the extreme summer heat in western Russia, flooding in Pakistan, intense wildfires in Australia, and drought in regions of the United States and elsewhere. The patterns of resulting changes in joint diseases due to infection from these conditions will vary regionally depending on altitude, latitude, storms, deforestation, desertification, urbanization, land use patterns, energy production, and transportation.

Dr. Muller highlighted changes in several diseases:

▸ Lyme disease. Lyme disease used to be limited to five U.S. geographic regions, but its geographic range has expanded into many areas of Canada as temperatures have become more hospitable to the rodents and deer that act as vectors and reservoirs, spreading into southern and northern Ontario, southern Québec, Manitoba, the Prairie Provinces, the Maritime Provinces, and British Columbia.

▸ Carrion's disease. Children bear the brunt of this reemerging disease that has spread to new areas between the jungle and highlands of Peru and Ecuador. Its symptoms take the form of bone pain, among others. Changes in sea surface temperatures that triggered extreme seasonal rain patterns known as El Niño events in the 1980s and 1990s were associated with a nearly fourfold increase in Carrion's disease in Peru's Ancash region.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Climate change has expanded geographic ranges of tick and parasite vectors, pushing some infectious diseases that cause joint pain in children into unfamiliar territory, Dr. Sigfrid A. Muller said at a dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Lyme disease has spread well into Canada, and leishmaniasis is moving north from Mexico into Texas, Arizona, Oklahoma, and Ohio. Reports of Chagas disease are increasing in the United States and Central and South America. Peru and Ecuador are seeing more Carrion's disease, said Dr. Muller, a dermatologist in Las Vegas and chair of the International Society of Dermatology's Climate Change Task Force.

Global warming may be debated in the popular media, but there is little controversy about it in the scientific literature, he said. June 2010 was the warmest month on record (combining global land and ocean average surface temperatures) and the 304th consecutive month with a global temperature above the 20th-century average, according to the National Oceanic and Atmospheric Administration.

Scientists predict changes already underway will warm the planet at least 2 or 3 degrees Centigrade this century, and perhaps double or triple that if humans don't alter the behaviors that contribute to climate change. Current scientific estimates suggest that an increase of 2 degrees Centigrade may be the “tipping point” that triggers irreversible changes (such as methane release from melting permafrost) with unpredictable but severe consequences for the planet and its inhabitants, Dr. Muller said.

Some projected changes already are being seen in the extreme summer heat in western Russia, flooding in Pakistan, intense wildfires in Australia, and drought in regions of the United States and elsewhere. The patterns of resulting changes in joint diseases due to infection from these conditions will vary regionally depending on altitude, latitude, storms, deforestation, desertification, urbanization, land use patterns, energy production, and transportation.

Dr. Muller highlighted changes in several diseases:

▸ Lyme disease. Lyme disease used to be limited to five U.S. geographic regions, but its geographic range has expanded into many areas of Canada as temperatures have become more hospitable to the rodents and deer that act as vectors and reservoirs, spreading into southern and northern Ontario, southern Québec, Manitoba, the Prairie Provinces, the Maritime Provinces, and British Columbia.

▸ Carrion's disease. Children bear the brunt of this reemerging disease that has spread to new areas between the jungle and highlands of Peru and Ecuador. Its symptoms take the form of bone pain, among others. Changes in sea surface temperatures that triggered extreme seasonal rain patterns known as El Niño events in the 1980s and 1990s were associated with a nearly fourfold increase in Carrion's disease in Peru's Ancash region.

SDEF and this news organization are owned by Elsevier.

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 – 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.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A small, retrospective study suggests that patients with aspirin-exacerbated respiratory disease may be safely desensitized to aspirin in an office setting rather than in a hospital.

Each of 15 patients who underwent a 1-day aspirin desensitization protocol in a clinic completed the protocol and ingested a cumulative total of 568 mg of aspirin on average by the end of the day. Each was then able to tolerate taking aspirin up to 650 mg b.i.d., Richard S. Dunn and Dr. Richard W. Hendershot reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In-hospital aspirin desensitization for patients with aspirin-exacerbated respiratory disease typically takes 2-3 days, and some clinicians recommend doing it in an ICU, said Mr. Dunn, a fourth-year medical student at the University of Utah, Salt Lake City. Dr. Hendershot is an allergy and immunology specialist with Intermountain Healthcare in Salt Lake City.

The outpatient protocol took 8-9 hours. The cost to desensitize a patient averaged $2,678 in the outpatient clinic, compared with an average daily cost for ICU care of $13,347 reported in the literature.

Desensitization started with application of intranasal ketorolac three times over half-hour intervals. Patients then ingested 81 mg of aspirin and increased the dose by 81 mg every 2 hours to a final dose of 325 mg.

They were closely monitored during the desensitization. No complications were seen in 56% of patients. FEV₁ (forced expiratory volume in 1 second) decreased by more than 20% in 19% of patients; 13% of patients developed flushing, and dyspnea or urticaria was each seen in 6% of patients.

Approximately 21% of people with asthma and 40% of patients with asthma who are dependent on glucocorticoids have aspirin-exacerbated respiratory disease. These patients often present with asthma, chronic rhinosinusitis, and nasal polyps. If they ingest a cyclooxygenase-1 inhibitor, they develop asthma symptoms, rhinorrhea, periorbital edema, urticaria, pruritus, angioedema, anaphylaxis, or other symptoms.

The design of the desensitization protocol was borrowed from a similar protocol that was tested in a controlled study of 100 patients (Ann. Allergy Asthma Immunol. 2010;105:130-5).

A patient who could not afford desensitization in the hospital inspired the development of the outpatient protocol that was used in the study.

The results suggest that aspirin desensitization for the treatment of aspirin-exacerbated respiratory disease can be done safely and efficaciously in the outpatient setting in less time and with less cost, compared with inpatient treatment protocols, the investigators concluded.

The investigators reported having no conflicts of interest.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.

SAN FRANCISCO – A 9-mm wheal after skin prick testing provided a 95% positive predictive value for egg or peanut allergy in an analysis of data from 5,000 12-month-old infants recruited from the general population.

The current clinical practice of diagnosing peanut or egg allergy in infants who develop wheals larger than 8 mm from skin prick testing is appropriate in the general population, Lyle Gurrin, Ph.D., and his associates reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Infants with a wheal of any size after a skin prick test were invited for a diagnostic oral food challenge unless they had a convincing reaction in the previous month.

The analysis included 181 infants who underwent peanut challenges, 310 with egg challenges, and 71 with sesame challenges. None of the wheal sizes after sesame challenges reached a 95% positive predictive value for allergy, said Dr. Gurrin of the University of Melbourne.

Previous studies have suggested skin-prick-test wheal sizes provide a 95% likelihood of food allergy if the wheal is 8 mm or larger for egg allergy and 7 mm or larger for peanut allergy. Most of those were small studies of high-risk patients drawn from clinics, not the general population. The studies included a broad range of ages and relied on a history of ingestion reaction rather than performing a formal food challenge.

The current analysis used data from the larger HealthNuts study, a population-based study of Australian 1-year-old infants that was conducted to identify the prevalence of food allergy and modifiable risk factors. Investigators recruited parents and infants at childhood immunization sessions, and 2,848 (73%) agreed to participate. Skin prick tests showed sensitization (a wheal of 1 mm or larger) to peanut in 9%, to raw egg white in 16%, and to sesame in 3% (J. Allergy Clin. Immunol. 2011;127:668-676.e2).

Oral food challenges in these sensitized patients proved that 3% of the entire cohort was allergic to peanut, 9% was allergic to raw egg 1%, and had sesame allergy. Of the infants with raw egg allergy, 80% were able to tolerate baked egg. Some infants were allergic to more than one food. Overall, more than 10% of the cohort had challenge-proven IgE-mediated allergy to one of the common allergenic foods of childhood.

Further analysis of wheal-size thresholds for diagnosis will stratify the findings by the presence or absence of eczema, a family history of allergy, and the ingestion/reaction history, Dr. Gurrin said.

A positive oral food challenge was defined as three or more concurrent, noncontact urticaria lasting at least 5 minutes, vomiting, periorbital angioedema, or anaphylaxis occurring within 2 hours of ingesting the test food.

No patients were excluded from the HealthNuts study due to severe eczema, said one of Dr. Gurrin’s study associates, Dr. Katrina Allen, also of the university.

Less than 1% of infants in the study were dark skinned, but demographic factors did not differ significantly between infants who were excluded from the study and those who were enrolled, she said during the question-and-answer session after Dr. Gurrin's presentation.

The demographic characteristics of infants in the HealthNuts study were similar to population data from the Perinatal Data Collection Unit, but the mothers of HealthNuts infants tended to be older than in the general population.

A brief questionnaire completed by parents who declined to participate in the HealthNuts study suggested that nonparticipating infants were less likely to have a family history of allergy and more likely to already be eating and tolerating peanuts.

The study was funded by the Australian National Health and Medical Research Council, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the U.S. Department of Defense, and the Australian Egg Corp. Dr. Gurrin and Dr. Allen said they had no relevant financial disclosures.