Heidi Splete

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson’s disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was "the first successful randomized, double-blind gene therapy trial for a neurological disorder" and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported online March 17 in the Lancet Neurology.

In the study, 22 Parkinson’s patients with Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the gene for glutamic acid decarboxylase (GAD) into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson’s disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson’s disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the "off" state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

"The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points" at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator’s clinical global impression of Parkinson’s disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients’ ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study’s small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, "it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product," the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, Dr. Hutchinson said. The significant difference in outcomes between the groups is "a tribute" to the researchers’ attention to detail in a small surgical trial, he added (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

The study was funded by Neurologix Inc. Many of the investigators reported serving as speakers or consultants or receiving grant funding from many companies that manufacture treatments for Parkinson’s disease. Dr. Hutchinson had no financial conflicts to disclose.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online at http://www.cdc.gov/Features/PreventiveServices.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services on March 14.

Approximately 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, according to the authors of the report, "Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap."

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults aged 65 and older said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. In addition, approximately 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions for improving preventive care for older adults, including promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual.

The report also recommended several additional preventive services for older adults: screening and counseling for alcohol misuse; zoster vaccination; aspirin use; blood pressure screening; cervical cancer screening; depression screening and counseling; and obesity screening and counseling.

The full report is available online.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register. The findings were published online Feb. 17 in the Annals of the Rheumatic Diseases.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy.

The study was limited by the smaller size of certain treatment groups, but it is the largest of its type to date. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

"Further study is required to understand if longer-term anti-TNF treatment persistence would be improved by simply stopping these DMARDs or whether they should be substituted, where possible, with other DMARDs such as MTX, if tolerated," they said.

The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.