Sherry Boschert

SAN FRANCISCO – A collaborative, community-based program to improve care for publicly insured children has reduced emergency department visits, hospitalizations, and costs, thanks in large part to a strong focus on asthma care.

Dr. Tom Peterson and his associates emulated a similar program at Denver Children’s Hospital to start the Children’s Healthcare Access Program (CHAP) for pediatric Medicaid recipients in Grand Rapids, Mich. Their 3-year-old program has been so successful that other Michigan counties are now copying it.

"It’s not just an asthma program, but asthma is the biggest and most collaborative project we’ve pulled together" in CHAP, he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In its first 3 years, CHAP connected almost 2,000 new Medicaid patients with clinicians and helped those clinicians access approximately $500,000 in provider incentives such as pay-for-performance incentives, he said. Of the approximately 15,300 children covered by CHAP, almost 6,000 were referred for CHAP services, including transportation for patients who might otherwise be no-shows for appointments.

In the CHAP population overall, emergency department visits decreased by 12% and hospitalizations decreased by 14%, reported Dr. Peterson, a pediatrician and executive director of safety, quality, and community health at Helen DeVos Children’s Hospital, Grand Rapids. Much greater decreases were seen in teaching clinics involved in CHAP.

Previous research by Dr. Peterson showed that children with public insurance or no insurance in Michigan were twice as likely to have asthma as were privately insured children (J. Pediatrics 2011;158:313-8.e2).

His hospital partnered with the Asthma Network of West Michigan and a managed care organization to pull together a group consisting of 40 pediatricians; 10-12 family physicians; and midlevel providers from four private practices, nine community- and school-based clinics, a pediatric resident teaching clinic, and a nurse practitioner clinic in CHAP.

The program features a team of six or seven people who help improve the children’s "medical homes" in primary care practices and help clinicians by coordinating the care. "Education is a significant piece of this, not just for the families but also for providers, sites, and patients," Dr. Peterson said.

CHAP can help practices improve efficiencies and scheduling. It helps coordinate care with mental health services, transportation, and other services. Education covers not just asthma but also flu shots, diet and nutrition, and inappropriate use of emergency departments. CHAP also acts as a neutral convener of meetings with community stakeholders (some of whom had never met together) to address systemic issues.

The asthma program within CHAP provides ongoing education and training of health care providers, families, and patients. High-risk children get monthly home-based visits for disease management for the first 6 months, then two visits in the next 6 months. CHAP pays attention to transitions of care between inpatient stays and medical homes, and now includes schools in postdischarge care. Services currently are provided by four certified, culturally skilled, multilingual asthma educators and two social workers, who may visit families to assist with psychosocial barriers to asthma care. CHAP also provides funding for home-based asthma case management through the Asthma Network of West Michigan.

Among seven high-risk children with asthma in CHAP’s case-management program, emergency department visits have decreased by 30% and hospitalizations have decreased by 63%, he said.

CHAP’s asthma team includes five pediatricians, asthma educators, an asthma and allergy specialist, school leaders or nurses, Medicaid health plan representatives and case managers, the Children’s Hospital quality improvement specialist, CHAP’s medical director and manager, and data analysts. "It’s a pretty diverse group of people to get together," Dr. Peterson said.

The CHAP team assesses participating medical practices for 12 characteristics "that we think constitute a really good asthma site," he said. These include asthma in-service training for staff and education for patients, having an in-office asthma educator, referring appropriate patients to CHAP or the Asthma Network of West Michigan, teaching peak flow monitoring, assessing exposure to environmental tobacco, in-office spirometry, use of management plans, the Asthma Control Test and an asthma registry, and routine 6-month asthma visits.

With 1 point allotted for each of the 12 factors, the average score of CHAP practices increased from 6 to 10 in the first 3 years of the program.

Priority Health, a managed care organization, provided kits for the program. CHAP is funded by the hospital and by a variety of private and corporate foundations, including the Douglas and Maria DeVos Foundation, W.K. Kellogg Foundation, Steelcase Foundation, Sebastian Foundation, Early Childhood Investment Corporation, Frey Foundation, Grand Rapids Community Foundation, Heart of West Michigan United Way, O’Donovan Family Foundation, and PNC Grow Up Great. Dr. Peterson said he has no conflicts of interest.

SAN FRANCISCO – A collaborative, community-based program to improve care for publicly insured children has reduced emergency department visits, hospitalizations, and costs, thanks in large part to a strong focus on asthma care.

Dr. Tom Peterson and his associates emulated a similar program at Denver Children’s Hospital to start the Children’s Healthcare Access Program (CHAP) for pediatric Medicaid recipients in Grand Rapids, Mich. Their 3-year-old program has been so successful that other Michigan counties are now copying it.

"It’s not just an asthma program, but asthma is the biggest and most collaborative project we’ve pulled together" in CHAP, he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In its first 3 years, CHAP connected almost 2,000 new Medicaid patients with clinicians and helped those clinicians access approximately $500,000 in provider incentives such as pay-for-performance incentives, he said. Of the approximately 15,300 children covered by CHAP, almost 6,000 were referred for CHAP services, including transportation for patients who might otherwise be no-shows for appointments.

In the CHAP population overall, emergency department visits decreased by 12% and hospitalizations decreased by 14%, reported Dr. Peterson, a pediatrician and executive director of safety, quality, and community health at Helen DeVos Children’s Hospital, Grand Rapids. Much greater decreases were seen in teaching clinics involved in CHAP.

Previous research by Dr. Peterson showed that children with public insurance or no insurance in Michigan were twice as likely to have asthma as were privately insured children (J. Pediatrics 2011;158:313-8.e2).

His hospital partnered with the Asthma Network of West Michigan and a managed care organization to pull together a group consisting of 40 pediatricians; 10-12 family physicians; and midlevel providers from four private practices, nine community- and school-based clinics, a pediatric resident teaching clinic, and a nurse practitioner clinic in CHAP.

The program features a team of six or seven people who help improve the children’s "medical homes" in primary care practices and help clinicians by coordinating the care. "Education is a significant piece of this, not just for the families but also for providers, sites, and patients," Dr. Peterson said.

CHAP can help practices improve efficiencies and scheduling. It helps coordinate care with mental health services, transportation, and other services. Education covers not just asthma but also flu shots, diet and nutrition, and inappropriate use of emergency departments. CHAP also acts as a neutral convener of meetings with community stakeholders (some of whom had never met together) to address systemic issues.

The asthma program within CHAP provides ongoing education and training of health care providers, families, and patients. High-risk children get monthly home-based visits for disease management for the first 6 months, then two visits in the next 6 months. CHAP pays attention to transitions of care between inpatient stays and medical homes, and now includes schools in postdischarge care. Services currently are provided by four certified, culturally skilled, multilingual asthma educators and two social workers, who may visit families to assist with psychosocial barriers to asthma care. CHAP also provides funding for home-based asthma case management through the Asthma Network of West Michigan.

Among seven high-risk children with asthma in CHAP’s case-management program, emergency department visits have decreased by 30% and hospitalizations have decreased by 63%, he said.

CHAP’s asthma team includes five pediatricians, asthma educators, an asthma and allergy specialist, school leaders or nurses, Medicaid health plan representatives and case managers, the Children’s Hospital quality improvement specialist, CHAP’s medical director and manager, and data analysts. "It’s a pretty diverse group of people to get together," Dr. Peterson said.

The CHAP team assesses participating medical practices for 12 characteristics "that we think constitute a really good asthma site," he said. These include asthma in-service training for staff and education for patients, having an in-office asthma educator, referring appropriate patients to CHAP or the Asthma Network of West Michigan, teaching peak flow monitoring, assessing exposure to environmental tobacco, in-office spirometry, use of management plans, the Asthma Control Test and an asthma registry, and routine 6-month asthma visits.

With 1 point allotted for each of the 12 factors, the average score of CHAP practices increased from 6 to 10 in the first 3 years of the program.

Priority Health, a managed care organization, provided kits for the program. CHAP is funded by the hospital and by a variety of private and corporate foundations, including the Douglas and Maria DeVos Foundation, W.K. Kellogg Foundation, Steelcase Foundation, Sebastian Foundation, Early Childhood Investment Corporation, Frey Foundation, Grand Rapids Community Foundation, Heart of West Michigan United Way, O’Donovan Family Foundation, and PNC Grow Up Great. Dr. Peterson said he has no conflicts of interest.

SAN FRANCISCO – A collaborative, community-based program to improve care for publicly insured children has reduced emergency department visits, hospitalizations, and costs, thanks in large part to a strong focus on asthma care.

Dr. Tom Peterson and his associates emulated a similar program at Denver Children’s Hospital to start the Children’s Healthcare Access Program (CHAP) for pediatric Medicaid recipients in Grand Rapids, Mich. Their 3-year-old program has been so successful that other Michigan counties are now copying it.

"It’s not just an asthma program, but asthma is the biggest and most collaborative project we’ve pulled together" in CHAP, he said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In its first 3 years, CHAP connected almost 2,000 new Medicaid patients with clinicians and helped those clinicians access approximately $500,000 in provider incentives such as pay-for-performance incentives, he said. Of the approximately 15,300 children covered by CHAP, almost 6,000 were referred for CHAP services, including transportation for patients who might otherwise be no-shows for appointments.

In the CHAP population overall, emergency department visits decreased by 12% and hospitalizations decreased by 14%, reported Dr. Peterson, a pediatrician and executive director of safety, quality, and community health at Helen DeVos Children’s Hospital, Grand Rapids. Much greater decreases were seen in teaching clinics involved in CHAP.

Previous research by Dr. Peterson showed that children with public insurance or no insurance in Michigan were twice as likely to have asthma as were privately insured children (J. Pediatrics 2011;158:313-8.e2).

His hospital partnered with the Asthma Network of West Michigan and a managed care organization to pull together a group consisting of 40 pediatricians; 10-12 family physicians; and midlevel providers from four private practices, nine community- and school-based clinics, a pediatric resident teaching clinic, and a nurse practitioner clinic in CHAP.

The program features a team of six or seven people who help improve the children’s "medical homes" in primary care practices and help clinicians by coordinating the care. "Education is a significant piece of this, not just for the families but also for providers, sites, and patients," Dr. Peterson said.

CHAP can help practices improve efficiencies and scheduling. It helps coordinate care with mental health services, transportation, and other services. Education covers not just asthma but also flu shots, diet and nutrition, and inappropriate use of emergency departments. CHAP also acts as a neutral convener of meetings with community stakeholders (some of whom had never met together) to address systemic issues.

The asthma program within CHAP provides ongoing education and training of health care providers, families, and patients. High-risk children get monthly home-based visits for disease management for the first 6 months, then two visits in the next 6 months. CHAP pays attention to transitions of care between inpatient stays and medical homes, and now includes schools in postdischarge care. Services currently are provided by four certified, culturally skilled, multilingual asthma educators and two social workers, who may visit families to assist with psychosocial barriers to asthma care. CHAP also provides funding for home-based asthma case management through the Asthma Network of West Michigan.

Among seven high-risk children with asthma in CHAP’s case-management program, emergency department visits have decreased by 30% and hospitalizations have decreased by 63%, he said.

CHAP’s asthma team includes five pediatricians, asthma educators, an asthma and allergy specialist, school leaders or nurses, Medicaid health plan representatives and case managers, the Children’s Hospital quality improvement specialist, CHAP’s medical director and manager, and data analysts. "It’s a pretty diverse group of people to get together," Dr. Peterson said.

The CHAP team assesses participating medical practices for 12 characteristics "that we think constitute a really good asthma site," he said. These include asthma in-service training for staff and education for patients, having an in-office asthma educator, referring appropriate patients to CHAP or the Asthma Network of West Michigan, teaching peak flow monitoring, assessing exposure to environmental tobacco, in-office spirometry, use of management plans, the Asthma Control Test and an asthma registry, and routine 6-month asthma visits.

With 1 point allotted for each of the 12 factors, the average score of CHAP practices increased from 6 to 10 in the first 3 years of the program.

Priority Health, a managed care organization, provided kits for the program. CHAP is funded by the hospital and by a variety of private and corporate foundations, including the Douglas and Maria DeVos Foundation, W.K. Kellogg Foundation, Steelcase Foundation, Sebastian Foundation, Early Childhood Investment Corporation, Frey Foundation, Grand Rapids Community Foundation, Heart of West Michigan United Way, O’Donovan Family Foundation, and PNC Grow Up Great. Dr. Peterson said he has no conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they've made some major changes.

A new section addresses diagnosis and classification of non-small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.

The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.

And it dumps the term �bronchioalveolar carcinoma� while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-85).

The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.

The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, �not only for pathologic staging but also for clinical staging,� said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.

The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel's statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.

Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.

P Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.

P Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.

P Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.

The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.

�Adenocarcinoma in situ� and �minimally invasive adenocarcinoma� appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.

The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype.

�This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings,�  according to Dr. Travis.

Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.

Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained.

�Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data,� he said.

One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca.

Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized.

The rest of the committee reported no financial conflicts of interest.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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