Elizabeth Mechcatie

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment "to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy "is extremely important and … will open the floodgates to this drug," Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

"Most people with metastatic melanoma will see this drug," said Dr. Sosman, coauthor of the pivotal trial. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said "may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors." It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients.

On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO's annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as "very good." Those with a true response (5%-10%) "do extremely well."

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. "That's the group that actually gets the drug, their tumors seem to grow, but then they stabilize," so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes "a large group of patients who don't technically have a response, but have a durable stabilization of their disease," Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

"Physicians will have to be enlightened in how to manage these patients," Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy "can easily spiral out of control" and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. "It's a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for," he said.

Metastatic melanoma has been an "incredibly frustrating disease," with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the "incredible durability" among the subset of responders, about 5%-10% of those treated. "We used to consider melanoma the graveyard for phase III studies," with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these "may change the whole nature of the disease."He foresaw combining a drug that does not have a high response rate but has "incredible durability" with a drug such as a BRAF inhibitor, with "an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well."

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment "to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy "is extremely important and … will open the floodgates to this drug," Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

"Most people with metastatic melanoma will see this drug," said Dr. Sosman, coauthor of the pivotal trial. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said "may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors." It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients.

On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO's annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as "very good." Those with a true response (5%-10%) "do extremely well."

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. "That's the group that actually gets the drug, their tumors seem to grow, but then they stabilize," so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes "a large group of patients who don't technically have a response, but have a durable stabilization of their disease," Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

"Physicians will have to be enlightened in how to manage these patients," Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy "can easily spiral out of control" and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. "It's a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for," he said.

Metastatic melanoma has been an "incredibly frustrating disease," with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the "incredible durability" among the subset of responders, about 5%-10% of those treated. "We used to consider melanoma the graveyard for phase III studies," with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these "may change the whole nature of the disease."He foresaw combining a drug that does not have a high response rate but has "incredible durability" with a drug such as a BRAF inhibitor, with "an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well."

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment "to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy "is extremely important and … will open the floodgates to this drug," Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

"Most people with metastatic melanoma will see this drug," said Dr. Sosman, coauthor of the pivotal trial. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said "may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors." It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients.

On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO's annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as "very good." Those with a true response (5%-10%) "do extremely well."

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. "That's the group that actually gets the drug, their tumors seem to grow, but then they stabilize," so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes "a large group of patients who don't technically have a response, but have a durable stabilization of their disease," Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

"Physicians will have to be enlightened in how to manage these patients," Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy "can easily spiral out of control" and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. "It's a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for," he said.

Metastatic melanoma has been an "incredibly frustrating disease," with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the "incredible durability" among the subset of responders, about 5%-10% of those treated. "We used to consider melanoma the graveyard for phase III studies," with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these "may change the whole nature of the disease."He foresaw combining a drug that does not have a high response rate but has "incredible durability" with a drug such as a BRAF inhibitor, with "an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well."

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

The long wait is over. The Food and Drug Administration has approved ipilimumab – the first drug ever proven to prolong survival in stage IV melanoma – in a down-to-the wire decision announced by the agency on March 25.

The approved indication in unresectable and metastatic melanoma comes with a risk management plan addressing life-threatening toxicity associated with the new immunotherapy, as was seen in a pivotal clinical trial conducted in previously treated patients.

Ipilimumab is the first FDA-approved treatment “to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment, Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, noted in the announcement.

It is being marketed by Bristol-Myers Squibb under the trade name Yervoy. The approved dose is 3 mg/kg administered intravenously over 90 minutes every 3 weeks for a total of four doses.

That the FDA did not specify a line of therapy “is extremely important and … will open the floodgates to this drug,” Dr. Jeffrey Sosman, Ingram Professor of Cancer Research, professor of medicine, and director of the melanoma program at Vanderbilt University, Nashville, said in an interview after the announcement.

“Most people with metastatic melanoma will see this drug,” said Dr. Sosman, coauthor of the pivotal trial and associate editor of The Oncology Report. The indication does not exclude untreated patients, he noted.

A monoclonal antibody administered intravenously, ipilimumab blocks cytotoxic T-lymphocyte antigen (CTLA-4), a molecule that the FDA said “may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells … [and] may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.” It is being studied in other cancers as well.

Approval was based on an international study of 676 patients with previously-treated unresectable stage III or IV melanoma whose disease had progressed. The study compared ipilimumab treatment with an experimental tumor vaccine (gp100), gp100 alone, and ipilimumab alone. Median overall survival was 10 months among those who received ipilimumab plus the vaccine, 10.1 months among those who received ipilimumab alone, and 6.4 months among those who received the vaccine alone (N. Engl. J. Med. 2010;363:711-23).

In the study, 10%-15% of patients on ipilimumab developed grade 3 or 4 immune-related adverse events, and 7 of the 14 deaths related to ipilimumab were associated with immune-related adverse events. The FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS) to educate health care professionals about the risks of the drug, and a medication guide to explain the risks of treatment to patients. On March 21, several days before ipilimumab was approved, drugmaker Bristol-Myers-Squibb announced that that it had met the primary end point, improvement in overall survival, in a separate phase III trial conducted in previously untreated patients. This study compared ipilimumab plus dacarbazine with dacarbazine alone. The company said it would submit an abstract with the results to the American Society of Clinical Oncology for presentation in June at ASCO’s annual meeting.

Dr. Sosman pointed out that the second study used a higher dose of ipilimumab (10 mg/kg), an issue that will need to be addressed, since mg/kg is the FDA-approved dose.

He described the durability of response with ipilimumab as “very good.” Those with a true response (5%-10%) “do extremely well.”

Another group of patients who do extremely well technically have progression of disease - a well-known phenomenon with this drug, he said. “That’s the group that actually gets the drug, their tumors seem to grow, but then they stabilize,” so that at the end of the first 12 weeks of treatment, their scans show progression, but later scans show regression. This describes “a large group of patients who don’t technically have a response, but have a durable stabilization of their disease,” Dr. Sosman said.

The toxicities associated with ipilimumab are of a different nature than those of chemotherapy, he said. (The boxed warning states that severe immune-mediated reactions require permanent discontinuation of ipilimumab and treatment with systemic, high-dose corticosteroids.)

“Physicians will have to be enlightened in how to manage these patients,” Dr. Sosman said. For example, diarrhea associated with ipilimumab therapy “can easily spiral out of control” and requires an aggressive response that includes colonoscopy to visualize the bowel, and steroid therapy.

Other significant toxicities include uveitis, hypophysitis that can be problematic despite hormone replacement, hepatitis, and, rarely, neurologic problems. “It’s a real spectrum that you need to be very aware of and conscientious about following patients [and] patients have to be aware of what to look for,” he said.

Metastatic melanoma has been an “incredibly frustrating disease,” with only one treatment – high dose interleukin-2 – approved since dacarbazine was approved in 1975, Dr. Sosman noted. The approval of interleukin-2 in 1998 was not based on overall survival benefit or high response rate, but the “incredible durability” among the subset of responders, about 5%-10% of those treated. “We used to consider melanoma the graveyard for phase III studies,” with every study of regimens and drugs turning out negative, he said.

Dr. Sosman emphasized there is still a lot to learn, and that studies of treatment combinations are crucial, as these “may change the whole nature of the disease.” He foresaw combining a drug that does not have a high response rate but has “incredible durability” with a drug such as a BRAF inhibitor, with “an extremely high response rate that causes a lot of tumor death rapidly and can even make a sick patient well.”

He predicted that dacarbazine will fall by the wayside and will not be used in studies. It has a response rate of 5%-10% has never been shown to improve survival, and does not have a history of durability, he said.

Dr. Sosman disclosed that his institution received a grant from study sponsors BMS and Medarex for participating in the phase III trial.

* UPDATE: This article was updated on 3/28/2011.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

School-age children with epilepsy are significantly more likely to have psychiatric symptoms than are their peers who did not have epilepsy a large Norwegian population-based study shows. The latest study confirms previous findings that identified the same association, according to the authors.

The results "provide further support regarding the high prevalence of psychiatric disorders in the epilepsy population," with multiple risk factors "contributing in a complex picture, also influenced by gender differences," concluded Dr. Kristin Å. Alfstad of the National Centre for Epilepsy at Oslo University Hospital and her colleagues.

Identifying high-risk groups "may help clinicians and provide the possibility for implementing interventions to prevent more serious problems from arising," they wrote in the study, which appeared online March 25 in Epilepsia (doi:10.1111/j.1528-1167.2011.03038.x).

Their findings are based on an analysis of parent responses in a health profile questionnaire completed in 2002 by almost 15,000 students aged 8-13 years and their parents living in a socioeconomically diverse area outside of Oslo. Questions included those pertaining to emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems.

The parents of 111 children reported their child as having or having had epilepsy. Among the 110 children (64 boys and 46 girls) with epilepsy whose questionnaires were completed, 38% had psychiatric symptoms, compared with 17% of the rest of the group, a statistically significant difference. The difference was evident in four areas: emotional problems, conduct problems, hyperactivity/inattention, and peer relationship problems. Emotional problems were more common among the girls, while problems with peer relationships and hyperactivity/inattention were more common among the boys.

In addition to epilepsy, low socioeconomic status was associated with psychiatric problems in the children, but with differences depending on gender: For example, when compared with the controls, the risk of having psychiatric symptoms was fourfold greater among the girls with epilepsy and about twofold greater among the boys with epilepsy; both significant differences. But in boys, the magnitude of the effects of low socioeconomic status on the risk of psychiatric symptoms was similar to that of having epilepsy. This was not seen in girls, for reasons the authors said were unclear, but might have been related to female adolescents having more negative attitudes toward having epilepsy than did male adolescents.

Referring to a 2003 large population-based study that found a 37% rate of psychopathology among children with epilepsy (Dev. Med. Child Neurol. 2003;45: 292-5) and a study published in 2006 (Epilepsy Behav. 2006;9:286-92) that also found a "comparable rate: Among children aged 13-16 years, "the current findings confirm the psychiatric comorbidity of epilepsy," the authors wrote.

More large-scale population-based studies that provide more specific data on epilepsy and possibly validating the psychiatric diagnosis "are needed to explore these problems further," and to study the link between psychopathology, gender, and age, they added.

"Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems," Dr. Alfstad said in a statement issued by the publisher of Epilepsia. "Identifying high-risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems."

The authors of the study had no disclosures related to the article. The study was financed by the National Centre for Epilepsy.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The warning about an increased risk of osteoporosis and fractures associated with proton pump inhibitors does not apply to over-the-counter formulations, the Food and Drug Administration announced March 23.

“Following a thorough review of available safety data, [the] FDA has concluded that fracture risk with short-term, low-dose PPI [proton pump inhibitor] use is unlikely,” the agency said in a statement. However, the statement pointed out that health care professionals “should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.”

The statement is a follow-up to an announcement the FDA made in May 2010, which said that the labels for OTC and prescription PPIs were being revised to include new information about the “possible” increases in the risk of hip, wrist, and spinal fractures associated with the use of these medications. The revision was based on an FDA review of several epidemiologic studies that reported an increased risk of these fractures with PPI use and indicated that treatment with high doses for 1 or more years was associated with the greatest risk.

But in the new statement, the FDA said that the available data show that patients at the greatest risk for fractures were treated with high doses of prescription PPIs, which are at doses higher than OTC PPI doses, and/or used a PPI for 1 or more years.

OTC PPIs in the United States are marketed as Prilosec OTC, Zegerid OTC, and Prevacid24HR.

Adverse reactions associated with PPIs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

GAITHERSBURG, MD. – A portable, battery-powered device that delivers electrical fields to the brain has a favorable risk-benefit profile in patients who have used up other treatment options for recurrent glioblastoma multiforme, according to a Food and Drug Administration advisory committee.

The FDA’s Neurological Devices Advisory Panel voted 7-3 with two abstentions on March 17 that the benefits of the NovoTTF-100A system exceed its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent glioblastoma multiforme (GBM).

Photo credit: ©Novocure

The device’s manufacturer, Israel-based Novocure Ltd., is seeking an indication in this population based on the results of a company-sponsored prospective randomized trial that compared treatment with the device to best standard of care (BSC) chemotherapy in 237 patients with recurrent GBM.

Panelists emphasized that the indication should reflect that patients have also failed chemotherapy options, and that while the treatment appears to be safe short term, the potential for chronic adverse effects should be monitored closely.

The device weighs about 6 pounds and is intended to be worn about 20 hours per day. It delivers "tumor treating fields" (TTF) via four electrodes placed on the scalp. This creates "a low intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division," according to the company. Normal cells are not affected, it said.

In the pivotal study, median overall survival, the primary end point, was 6.3 months among those treated with the device and 6.4 months among those treated with the best available chemotherapy. Investigators have presented subgroup analyses showing better survival in some populations.

Both the FDA and the panelists had concerns about methodologic problems in the study, which was designed to show that TTF therapy is superior to the best standard of care chemotherapy. But those voting positively cited the safety of the device, and evidence that it benefited some patients with few treatment options. Median survival of patients diagnosed with GBM is 15 months, and the 5-year overall survival rate is less than 10%, according to data cited by the company and the FDA.

NovoCure is conducting a phase III study of the device in patients with newly diagnosed GBM, in combination with temozolomide. The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The FDA usually follows the recommendations of its advisory committees. Panel members have been cleared of potential conflicts of interest by the FDA before meetings.

GAITHERSBURG, MD. – A portable, battery-powered device that delivers electrical fields to the brain has a favorable risk-benefit profile in patients who have used up other treatment options for recurrent glioblastoma multiforme, according to a Food and Drug Administration advisory committee.

The FDA’s Neurological Devices Advisory Panel voted 7-3 with two abstentions on March 17 that the benefits of the NovoTTF-100A system exceed its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent glioblastoma multiforme (GBM).

Photo credit: ©Novocure

The device’s manufacturer, Israel-based Novocure Ltd., is seeking an indication in this population based on the results of a company-sponsored prospective randomized trial that compared treatment with the device to best standard of care (BSC) chemotherapy in 237 patients with recurrent GBM.

Panelists emphasized that the indication should reflect that patients have also failed chemotherapy options, and that while the treatment appears to be safe short term, the potential for chronic adverse effects should be monitored closely.

The device weighs about 6 pounds and is intended to be worn about 20 hours per day. It delivers "tumor treating fields" (TTF) via four electrodes placed on the scalp. This creates "a low intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division," according to the company. Normal cells are not affected, it said.

In the pivotal study, median overall survival, the primary end point, was 6.3 months among those treated with the device and 6.4 months among those treated with the best available chemotherapy. Investigators have presented subgroup analyses showing better survival in some populations.

Both the FDA and the panelists had concerns about methodologic problems in the study, which was designed to show that TTF therapy is superior to the best standard of care chemotherapy. But those voting positively cited the safety of the device, and evidence that it benefited some patients with few treatment options. Median survival of patients diagnosed with GBM is 15 months, and the 5-year overall survival rate is less than 10%, according to data cited by the company and the FDA.

NovoCure is conducting a phase III study of the device in patients with newly diagnosed GBM, in combination with temozolomide. The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The FDA usually follows the recommendations of its advisory committees. Panel members have been cleared of potential conflicts of interest by the FDA before meetings.

GAITHERSBURG, MD. – A portable, battery-powered device that delivers electrical fields to the brain has a favorable risk-benefit profile in patients who have used up other treatment options for recurrent glioblastoma multiforme, according to a Food and Drug Administration advisory committee.

The FDA’s Neurological Devices Advisory Panel voted 7-3 with two abstentions on March 17 that the benefits of the NovoTTF-100A system exceed its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent glioblastoma multiforme (GBM).

Photo credit: ©Novocure

The device’s manufacturer, Israel-based Novocure Ltd., is seeking an indication in this population based on the results of a company-sponsored prospective randomized trial that compared treatment with the device to best standard of care (BSC) chemotherapy in 237 patients with recurrent GBM.

Panelists emphasized that the indication should reflect that patients have also failed chemotherapy options, and that while the treatment appears to be safe short term, the potential for chronic adverse effects should be monitored closely.

The device weighs about 6 pounds and is intended to be worn about 20 hours per day. It delivers "tumor treating fields" (TTF) via four electrodes placed on the scalp. This creates "a low intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division," according to the company. Normal cells are not affected, it said.

In the pivotal study, median overall survival, the primary end point, was 6.3 months among those treated with the device and 6.4 months among those treated with the best available chemotherapy. Investigators have presented subgroup analyses showing better survival in some populations.

Both the FDA and the panelists had concerns about methodologic problems in the study, which was designed to show that TTF therapy is superior to the best standard of care chemotherapy. But those voting positively cited the safety of the device, and evidence that it benefited some patients with few treatment options. Median survival of patients diagnosed with GBM is 15 months, and the 5-year overall survival rate is less than 10%, according to data cited by the company and the FDA.

NovoCure is conducting a phase III study of the device in patients with newly diagnosed GBM, in combination with temozolomide. The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The FDA usually follows the recommendations of its advisory committees. Panel members have been cleared of potential conflicts of interest by the FDA before meetings.