Heidi Splete

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.

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.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.