Amy Karon

Each 6.5-cm decrease in adult height was linked to a 13.5% rise in the risk of coronary artery disease, investigators reported online in the New England Journal of Medicine.

An association between shorter height and lipid abnormalities could partially explain the finding, but the study also found overlapping biological pathways that contribute to both adult height and atherosclerosis, said Dr. Christopher Nelson at the University of Leicester in the United Kingdom and his associates. “Our study validates the epidemiologic observation of an inverse association between height and coronary artery disease,” they said.

©Kativ/iStockphoto

Past studies have linked shorter adult height with coronary artery disease (CAD) and relevant risk factors such as diabetes and high LDL cholesterol. To explore genetic reasons for the association, the investigators analyzed 180 single-nucleotide polymorphisms (SNPs) known to account for about 10% of the variation in adult height, using data from more than 18,000 individuals. They also modeled the link between CAD and final adult height among more than 128,300 controls and more than 650,000 individuals with a history of myocardial infarction, coronary revascularization, or angiographic coronary disease (N. Engl. J. Med. 2015 Apr. 8 [doi:10.1056/NEJMoa1404881]). Risk of CAD rose by 13.5% for each 6.5-cm (1 standard deviation) decrease in adult height, while having relatively more height-promoting SNPs was significantly protective against CAD, said the researchers. Among 12 risk factors for CAD, only LDL cholesterol and triglycerides achieved significance in the model, and these accounted for only about 30% of total CAD risk, they reported.

The analysis also revealed several genetic pathways that influenced adult height and atherosclerosis, including BMP- and TGF-beta-signaling pathways, axon-guidance pathways, and the STAT3 and IGF-I pathways, the investigators reported. “Taken together, these findings suggest that several overlapping and complex biologic pathways on the one hand influence development and height and on the other hand influence the risk of atherosclerosis through an effect on vascular biology and function,” they said.

Notably, the study found no significant inverse link between CAD and height among women. “Whether this represents a genuine difference in the effect of genetically determined height on the risk of CAD between men and women, or simply reflects the reduced power from the much smaller sample size available for analysis in women is unclear,” the investigators said.

The study was funded by the British Heart Foundation, the United Kingdom National Institute for Health Research, the European Union project CVgenes@target, and the Leducq Foundation. Several coauthors reported grant support from research foundations and/or receiving grants, lecture, consulting, or advisory board fees from pharmaceutical companies.

Each 6.5-cm decrease in adult height was linked to a 13.5% rise in the risk of coronary artery disease, investigators reported online in the New England Journal of Medicine.

An association between shorter height and lipid abnormalities could partially explain the finding, but the study also found overlapping biological pathways that contribute to both adult height and atherosclerosis, said Dr. Christopher Nelson at the University of Leicester in the United Kingdom and his associates. “Our study validates the epidemiologic observation of an inverse association between height and coronary artery disease,” they said.

©Kativ/iStockphoto

Past studies have linked shorter adult height with coronary artery disease (CAD) and relevant risk factors such as diabetes and high LDL cholesterol. To explore genetic reasons for the association, the investigators analyzed 180 single-nucleotide polymorphisms (SNPs) known to account for about 10% of the variation in adult height, using data from more than 18,000 individuals. They also modeled the link between CAD and final adult height among more than 128,300 controls and more than 650,000 individuals with a history of myocardial infarction, coronary revascularization, or angiographic coronary disease (N. Engl. J. Med. 2015 Apr. 8 [doi:10.1056/NEJMoa1404881]). Risk of CAD rose by 13.5% for each 6.5-cm (1 standard deviation) decrease in adult height, while having relatively more height-promoting SNPs was significantly protective against CAD, said the researchers. Among 12 risk factors for CAD, only LDL cholesterol and triglycerides achieved significance in the model, and these accounted for only about 30% of total CAD risk, they reported.

The analysis also revealed several genetic pathways that influenced adult height and atherosclerosis, including BMP- and TGF-beta-signaling pathways, axon-guidance pathways, and the STAT3 and IGF-I pathways, the investigators reported. “Taken together, these findings suggest that several overlapping and complex biologic pathways on the one hand influence development and height and on the other hand influence the risk of atherosclerosis through an effect on vascular biology and function,” they said.

Notably, the study found no significant inverse link between CAD and height among women. “Whether this represents a genuine difference in the effect of genetically determined height on the risk of CAD between men and women, or simply reflects the reduced power from the much smaller sample size available for analysis in women is unclear,” the investigators said.

The study was funded by the British Heart Foundation, the United Kingdom National Institute for Health Research, the European Union project CVgenes@target, and the Leducq Foundation. Several coauthors reported grant support from research foundations and/or receiving grants, lecture, consulting, or advisory board fees from pharmaceutical companies.

Each 6.5-cm decrease in adult height was linked to a 13.5% rise in the risk of coronary artery disease, investigators reported online in the New England Journal of Medicine.

An association between shorter height and lipid abnormalities could partially explain the finding, but the study also found overlapping biological pathways that contribute to both adult height and atherosclerosis, said Dr. Christopher Nelson at the University of Leicester in the United Kingdom and his associates. “Our study validates the epidemiologic observation of an inverse association between height and coronary artery disease,” they said.

©Kativ/iStockphoto

Past studies have linked shorter adult height with coronary artery disease (CAD) and relevant risk factors such as diabetes and high LDL cholesterol. To explore genetic reasons for the association, the investigators analyzed 180 single-nucleotide polymorphisms (SNPs) known to account for about 10% of the variation in adult height, using data from more than 18,000 individuals. They also modeled the link between CAD and final adult height among more than 128,300 controls and more than 650,000 individuals with a history of myocardial infarction, coronary revascularization, or angiographic coronary disease (N. Engl. J. Med. 2015 Apr. 8 [doi:10.1056/NEJMoa1404881]). Risk of CAD rose by 13.5% for each 6.5-cm (1 standard deviation) decrease in adult height, while having relatively more height-promoting SNPs was significantly protective against CAD, said the researchers. Among 12 risk factors for CAD, only LDL cholesterol and triglycerides achieved significance in the model, and these accounted for only about 30% of total CAD risk, they reported.

The analysis also revealed several genetic pathways that influenced adult height and atherosclerosis, including BMP- and TGF-beta-signaling pathways, axon-guidance pathways, and the STAT3 and IGF-I pathways, the investigators reported. “Taken together, these findings suggest that several overlapping and complex biologic pathways on the one hand influence development and height and on the other hand influence the risk of atherosclerosis through an effect on vascular biology and function,” they said.

Notably, the study found no significant inverse link between CAD and height among women. “Whether this represents a genuine difference in the effect of genetically determined height on the risk of CAD between men and women, or simply reflects the reduced power from the much smaller sample size available for analysis in women is unclear,” the investigators said.

The study was funded by the British Heart Foundation, the United Kingdom National Institute for Health Research, the European Union project CVgenes@target, and the Leducq Foundation. Several coauthors reported grant support from research foundations and/or receiving grants, lecture, consulting, or advisory board fees from pharmaceutical companies.

Requiring patients to meet at least two criteria for systemic inflammatory response syndrome (SIRS) excluded one in every eight patients with infection and organ failure, and did not help predict mortality, according to a large multicenter retrospective study.

Patients with SIRS-negative severe sepsis had “substantial mortality and … epidemiologic characteristics and changes that were essentially identical to those of patients with SIRS-positive severe sepsis,” wrote Dr. Kirsi-Maija Kaukonen at Monash University in Melbourne, and her associates. “Our findings challenge the sensitivity, face validity, and construct validity of the rule regarding two or more SIRS criteria in diagnosing or defining severe sepsis in patients in the ICU,” the researchers wrote in a report in the New England Journal of Medicine, published simultaneously with their presentation at the annual meeting of the International Society on Intensive Care and Emergency Medicine.

©Andrei Malov/Thinkstock.com

Since 1992, the American College of Chest Physicians and Society of Critical Care Medicine have defined severe sepsis as suspected or proven infection, organ failure, and signs that meet at least two SIRS criteria. But affected elderly patients and those who take medications that affect heart rate, respiratory rate, or body temperature might not meet the definition, the researchers said (N. Eng. J. Med. 2015 [doi:10.1056/NEJMoa1415236]).

To test the validity of the definition, they retrospectively studied 109,663 patients with infection and organ failure treated over 14 years at 172 intensive care units in Australia and New Zealand. About 88% of patients had SIRS-positive severe sepsis, while 12% had SIRS-negative severe sepsis.

The two groups had similar characteristic and declines in mortality (for SIRS-positive patients, a drop from 36% to 18.3%; for SIRS-negative patients, a decrease from 27% to 9%; P = .12 for between-group difference), reported the investigators. The odds of mortality rose linearly by about 13% for each additional SIRS criterion (odds ratio, 1.13; 95% confidence interval, 1.11-1.15; P < .001), but there was no additional increase in mortality risk at the two-criteria threshold. Rates of discharge to rehabilitation and long-term care facilities also were similar between the two groups.

Applying the two-SIRS criterion within 24 hours of ICU admission – the most common time window for recruitment into sepsis trials – would exclude about one in every eight patients with infection and organ failure, the investigators concluded. “These patients have substantial mortality and their epidemiologic data are identical to those of patients with classic SIRS-positive severe sepsis, which suggests that these two groups represent different clinical phenotypes of the same process,” they wrote.

The Australian and New Zealand Intensive Care Research Centre funded the study. Dr. Kaukonen reported receiving grant support from the Academy of Finland. The other authors declared no relevant conflicts of interest.

Requiring patients to meet at least two criteria for systemic inflammatory response syndrome (SIRS) excluded one in every eight patients with infection and organ failure, and did not help predict mortality, according to a large multicenter retrospective study.

Patients with SIRS-negative severe sepsis had “substantial mortality and … epidemiologic characteristics and changes that were essentially identical to those of patients with SIRS-positive severe sepsis,” wrote Dr. Kirsi-Maija Kaukonen at Monash University in Melbourne, and her associates. “Our findings challenge the sensitivity, face validity, and construct validity of the rule regarding two or more SIRS criteria in diagnosing or defining severe sepsis in patients in the ICU,” the researchers wrote in a report in the New England Journal of Medicine, published simultaneously with their presentation at the annual meeting of the International Society on Intensive Care and Emergency Medicine.

©Andrei Malov/Thinkstock.com

Since 1992, the American College of Chest Physicians and Society of Critical Care Medicine have defined severe sepsis as suspected or proven infection, organ failure, and signs that meet at least two SIRS criteria. But affected elderly patients and those who take medications that affect heart rate, respiratory rate, or body temperature might not meet the definition, the researchers said (N. Eng. J. Med. 2015 [doi:10.1056/NEJMoa1415236]).

To test the validity of the definition, they retrospectively studied 109,663 patients with infection and organ failure treated over 14 years at 172 intensive care units in Australia and New Zealand. About 88% of patients had SIRS-positive severe sepsis, while 12% had SIRS-negative severe sepsis.

The two groups had similar characteristic and declines in mortality (for SIRS-positive patients, a drop from 36% to 18.3%; for SIRS-negative patients, a decrease from 27% to 9%; P = .12 for between-group difference), reported the investigators. The odds of mortality rose linearly by about 13% for each additional SIRS criterion (odds ratio, 1.13; 95% confidence interval, 1.11-1.15; P < .001), but there was no additional increase in mortality risk at the two-criteria threshold. Rates of discharge to rehabilitation and long-term care facilities also were similar between the two groups.

Applying the two-SIRS criterion within 24 hours of ICU admission – the most common time window for recruitment into sepsis trials – would exclude about one in every eight patients with infection and organ failure, the investigators concluded. “These patients have substantial mortality and their epidemiologic data are identical to those of patients with classic SIRS-positive severe sepsis, which suggests that these two groups represent different clinical phenotypes of the same process,” they wrote.

The Australian and New Zealand Intensive Care Research Centre funded the study. Dr. Kaukonen reported receiving grant support from the Academy of Finland. The other authors declared no relevant conflicts of interest.

Requiring patients to meet at least two criteria for systemic inflammatory response syndrome (SIRS) excluded one in every eight patients with infection and organ failure, and did not help predict mortality, according to a large multicenter retrospective study.

Patients with SIRS-negative severe sepsis had “substantial mortality and … epidemiologic characteristics and changes that were essentially identical to those of patients with SIRS-positive severe sepsis,” wrote Dr. Kirsi-Maija Kaukonen at Monash University in Melbourne, and her associates. “Our findings challenge the sensitivity, face validity, and construct validity of the rule regarding two or more SIRS criteria in diagnosing or defining severe sepsis in patients in the ICU,” the researchers wrote in a report in the New England Journal of Medicine, published simultaneously with their presentation at the annual meeting of the International Society on Intensive Care and Emergency Medicine.

©Andrei Malov/Thinkstock.com

Since 1992, the American College of Chest Physicians and Society of Critical Care Medicine have defined severe sepsis as suspected or proven infection, organ failure, and signs that meet at least two SIRS criteria. But affected elderly patients and those who take medications that affect heart rate, respiratory rate, or body temperature might not meet the definition, the researchers said (N. Eng. J. Med. 2015 [doi:10.1056/NEJMoa1415236]).

To test the validity of the definition, they retrospectively studied 109,663 patients with infection and organ failure treated over 14 years at 172 intensive care units in Australia and New Zealand. About 88% of patients had SIRS-positive severe sepsis, while 12% had SIRS-negative severe sepsis.

The two groups had similar characteristic and declines in mortality (for SIRS-positive patients, a drop from 36% to 18.3%; for SIRS-negative patients, a decrease from 27% to 9%; P = .12 for between-group difference), reported the investigators. The odds of mortality rose linearly by about 13% for each additional SIRS criterion (odds ratio, 1.13; 95% confidence interval, 1.11-1.15; P < .001), but there was no additional increase in mortality risk at the two-criteria threshold. Rates of discharge to rehabilitation and long-term care facilities also were similar between the two groups.

Applying the two-SIRS criterion within 24 hours of ICU admission – the most common time window for recruitment into sepsis trials – would exclude about one in every eight patients with infection and organ failure, the investigators concluded. “These patients have substantial mortality and their epidemiologic data are identical to those of patients with classic SIRS-positive severe sepsis, which suggests that these two groups represent different clinical phenotypes of the same process,” they wrote.

The Australian and New Zealand Intensive Care Research Centre funded the study. Dr. Kaukonen reported receiving grant support from the Academy of Finland. The other authors declared no relevant conflicts of interest.

SAN FRANCISCO – An investigational topical sebum inhibitor met its primary endpoints in a phase IIa trial, significantly reducing inflammatory and noninflammatory lesions in patients with facial acne vulgaris, researchers reported at the annual meeting of the American Academy of Dermatology.

“This study demonstrated that DRM01, belonging to a novel class of topical acne therapeutic agents, is well tolerated and shows evidence of efficacy for treatment of facial acne vulgaris,” said Dr. Robert Bissonnette of Innovaderm Research. Patients had no serious adverse events related to treatment, although the topical product caused erythema at the application site, he said.

The DRM01 agent inhibits sebum production by competing with acetyl coenzyme A carboxylase, which facilitates the first and rate-limiting step in fatty acid synthesis. “It has shown pronounced impact on triacylglycerols, which are considered the most important component of sebum in acne vulgaris,” said Dr. Bissonnette.

The researchers randomized 108 patients with moderate to severe facial acne to 12 weeks of twice-daily treatment with either 7.5% DRM01 or the vehicle gel. On average, patients had 29 inflammatory lesions and 40 noninflammatory lesions at baseline, and approximately two-thirds were women.

At week 12, the DRM01 group had an average 63.9% reduction in inflammatory lesions, compared with 45.9% for the vehicle control group (P < .001), Dr. Bissonnette said. The DRM01 group also had a 48.1% reduction in non-inflammatory lesions, compared with 28.8% for the control group (P =.003). Furthermore, 24.5% of patients who received DRM01 improved by at least two grades on the Investigator’s Global Assessment score, compared with only 7.3% of the control group (P = .007).

Most adverse events were mild or moderate and affected similar proportions of patients in each group, said Dr. Bissonnette. More than 5% of patients in both groups experienced application site dryness, burning, and stinging, but only patients in the treatment group reported application site erythema, he said. Nasopharyngitis affected 24.5% of patients treated with DRM01 and 12.7% of those treated with the vehicle, but was considered unrelated to treatment.

Researchers do not know how or whether DRM01 reduces inflammation, Dr. Bissonnette said in response to a question from an audience member. The study also was not able to show that DRM01 significantly reduced sebum production compared with the gel vehicle. “It could be a data quality problem, as the sites had not all been fully trained in doing those measurements,” he said.

Dermira manufactures DRM01 and sponsored the study. Dr. Bissonnette reported having served as a researcher for Dermira.

SAN FRANCISCO – An investigational topical sebum inhibitor met its primary endpoints in a phase IIa trial, significantly reducing inflammatory and noninflammatory lesions in patients with facial acne vulgaris, researchers reported at the annual meeting of the American Academy of Dermatology.

“This study demonstrated that DRM01, belonging to a novel class of topical acne therapeutic agents, is well tolerated and shows evidence of efficacy for treatment of facial acne vulgaris,” said Dr. Robert Bissonnette of Innovaderm Research. Patients had no serious adverse events related to treatment, although the topical product caused erythema at the application site, he said.

The DRM01 agent inhibits sebum production by competing with acetyl coenzyme A carboxylase, which facilitates the first and rate-limiting step in fatty acid synthesis. “It has shown pronounced impact on triacylglycerols, which are considered the most important component of sebum in acne vulgaris,” said Dr. Bissonnette.

The researchers randomized 108 patients with moderate to severe facial acne to 12 weeks of twice-daily treatment with either 7.5% DRM01 or the vehicle gel. On average, patients had 29 inflammatory lesions and 40 noninflammatory lesions at baseline, and approximately two-thirds were women.

At week 12, the DRM01 group had an average 63.9% reduction in inflammatory lesions, compared with 45.9% for the vehicle control group (P < .001), Dr. Bissonnette said. The DRM01 group also had a 48.1% reduction in non-inflammatory lesions, compared with 28.8% for the control group (P =.003). Furthermore, 24.5% of patients who received DRM01 improved by at least two grades on the Investigator’s Global Assessment score, compared with only 7.3% of the control group (P = .007).

Most adverse events were mild or moderate and affected similar proportions of patients in each group, said Dr. Bissonnette. More than 5% of patients in both groups experienced application site dryness, burning, and stinging, but only patients in the treatment group reported application site erythema, he said. Nasopharyngitis affected 24.5% of patients treated with DRM01 and 12.7% of those treated with the vehicle, but was considered unrelated to treatment.

Researchers do not know how or whether DRM01 reduces inflammation, Dr. Bissonnette said in response to a question from an audience member. The study also was not able to show that DRM01 significantly reduced sebum production compared with the gel vehicle. “It could be a data quality problem, as the sites had not all been fully trained in doing those measurements,” he said.

Dermira manufactures DRM01 and sponsored the study. Dr. Bissonnette reported having served as a researcher for Dermira.

SAN FRANCISCO – An investigational topical sebum inhibitor met its primary endpoints in a phase IIa trial, significantly reducing inflammatory and noninflammatory lesions in patients with facial acne vulgaris, researchers reported at the annual meeting of the American Academy of Dermatology.

“This study demonstrated that DRM01, belonging to a novel class of topical acne therapeutic agents, is well tolerated and shows evidence of efficacy for treatment of facial acne vulgaris,” said Dr. Robert Bissonnette of Innovaderm Research. Patients had no serious adverse events related to treatment, although the topical product caused erythema at the application site, he said.

The DRM01 agent inhibits sebum production by competing with acetyl coenzyme A carboxylase, which facilitates the first and rate-limiting step in fatty acid synthesis. “It has shown pronounced impact on triacylglycerols, which are considered the most important component of sebum in acne vulgaris,” said Dr. Bissonnette.

The researchers randomized 108 patients with moderate to severe facial acne to 12 weeks of twice-daily treatment with either 7.5% DRM01 or the vehicle gel. On average, patients had 29 inflammatory lesions and 40 noninflammatory lesions at baseline, and approximately two-thirds were women.

At week 12, the DRM01 group had an average 63.9% reduction in inflammatory lesions, compared with 45.9% for the vehicle control group (P < .001), Dr. Bissonnette said. The DRM01 group also had a 48.1% reduction in non-inflammatory lesions, compared with 28.8% for the control group (P =.003). Furthermore, 24.5% of patients who received DRM01 improved by at least two grades on the Investigator’s Global Assessment score, compared with only 7.3% of the control group (P = .007).

Most adverse events were mild or moderate and affected similar proportions of patients in each group, said Dr. Bissonnette. More than 5% of patients in both groups experienced application site dryness, burning, and stinging, but only patients in the treatment group reported application site erythema, he said. Nasopharyngitis affected 24.5% of patients treated with DRM01 and 12.7% of those treated with the vehicle, but was considered unrelated to treatment.

Researchers do not know how or whether DRM01 reduces inflammation, Dr. Bissonnette said in response to a question from an audience member. The study also was not able to show that DRM01 significantly reduced sebum production compared with the gel vehicle. “It could be a data quality problem, as the sites had not all been fully trained in doing those measurements,” he said.

Dermira manufactures DRM01 and sponsored the study. Dr. Bissonnette reported having served as a researcher for Dermira.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

SAN FRANCISCO – An investigational interleukin-23 inhibitor for moderate to severe plaque psoriasis achieved almost twice the PASI 90 response rate of ustekinumab and generated no major safety signals, based on data from randomized trial of 166 patients.

At 12 weeks, 77% of patients treated with 90- or 180-mg doses of BI 655066 were clear or almost clear, compared with 40% of patients treated with weight-based ustekinumab (P < .0001), Dr. Kim A. Papp reported at the annual meeting of the American Academy of Dermatology.

Response to the 180-mg dose of BI 655066 was both early and durable, he noted. “At 4 weeks, we were starting to see these patients do very well. At week 12, almost 80% of patients who received the 180-mg dose achieved PASI 90, and that response was maintained through 24 weeks,” he said. In contrast, the 90-mg dose of BI 65506 was associated with a decline in PASI 90 response after week 16, added Dr. Papp of Probity Medical Research in Waterloo, Ontario.

Past studies have shown that IL-23 plays a key role in psoriasis by mediating the Th17 cell pathway. The BI 655066 agent is a monoclonal antibody that selectively targets IL23p19, while ustekinumab (STELARA) is an IL12/23 antagonist approved for treatment of moderate or severe plaque psoriasis or active psoriatic arthritis. To compare the two biologics, Dr. Papp and his associates randomized 166 patients with moderate or severe plaque psoriasis to subcutaneous treatment with BI 655066 (18 mg at baseline, 90 mg at baseline and week 4, or 180 mg at baseline and week 4) or weight-based ustekinumab (45 or 90 mg at baseline and week 4.) The patient cohorts were demographically similar, had comparable histories of exposure to anti–tumor necrosis factor agents, and their average baseline PASI scores were about 19 to 20, said Dr. Papp.

In all, 90% of patients treated with 90- or 180-mg doses of BI 655066 had achieved static Physicians Global Assessment scores of clear or almost clear at week 12, compared with 67.5% of patients who received ustekinumab, Dr. Papp reported. Furthermore, 46% of BI 655066 patients achieved PASI 100 (complete clearing) at week 12, compared with 17.5% of ustekinumab patients. At week 20, PASI 100 response rates were 62% for the 180-mg group, 53% for the 90-mg group, and 30% for the ustekinumab group, he said.

Rates of adverse events were low and similar for the treatment groups, said Dr. Papp. The most common adverse events were nasopharyngitis and headache, although some patients reported arthralgia and myalgia. The investigators identified no severe or serious treatment-related side effects, nor any sign that adverse effects were more common at higher treatment doses, Dr. Papp said.

Researchers are continuing to assess the safety and efficacy of BI 655066 in an open-label extension trial of patients with plaque psoriasis. That study is using week 48 PASI 90 response as its primary endpoint and will track adverse events for 24 months.

Boehringer Ingelheim funded the study. Dr. Papp disclosed reported relevant relationships with Boehringer Ingelheim and with several other pharmaceutical companies.

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.

“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”

The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.

The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”

For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”

The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”

Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.

Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.

Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”

Finally, the ACR position statement recommended that biosimilars have distinctive names to easily distinguish them from their reference agents. Otherwise, name confusion could lead to prescribing errors and mistakes during surveillance for adverse events, the organization said.

“We will continue to follow the various issues surrounding the distribution, monitoring, and reimbursement of biosimilars very closely as state and federal policies are proposed that affect our patients and the rheumatologists who serve them,” Dr. St.Clair concluded. “Ensuring patients have easy access to affordable treatment options and rheumatology care continues to be a high priority for us.”

SAN FRANCISCO – Weekly treatment with 40 mg of adalimumab yielded the strongest clinical responses in adults with moderate to severe hidradenitis suppurativa with a safety profile similar to less intensive doses, according to data from two phase III trials.

Overall, 43% of adalimumab-treated patients achieved the predefined clinical response at 36 weeks, compared with 28% of patients who first received adalimumab and switched to placebo, Dr. Alexa Kimball said at the annual meeting of the American Academy of Dermatology. The 40-mg weekly dose also beat placebo in demographic subgroup analyses, said Dr. Kimball, professor of dermatology at Harvard Medical School in Boston. “Greater responses rates with this dose, combined with no difference in safety across the three treatment arms, suggests that weekly dosing was the optimal medium-term dosing strategy in hidradenitis suppurativa,” she added.

Hidradenitis suppurativa (also called acne inversa) is a chronic follicular occlusive skin disease that affects about 1%-4% of adults, particularly women, smokers, and obese or overweight patients. The disease has very few treatment options. Patients can develop recurrent abscesses, draining sinuses, and scarring, all of which negatively affect quality of life.

Adalimumab is an anti–tumor necrosis factor–alpha agent that previously bested placebo for hidradenitis suppurativa in phase II trials. Dr. Kimball and associates analyzed data on 633 patients with moderate to severe disease from two phase III, placebo-controlled trials (PIONEER I and II). For the first 12 weeks, patients were randomized to placebo or to 40 mg of adalimumab weekly. At week 12, patients were rerandomized to 40 mg adalimumab weekly, 40 mg of adalimumab every other week, or to placebo. The researchers defined treatment response as at least a 50% drop in abscesses and inflammatory nodules, with no numerical increase in individual numbers of abscesses or draining fistulas.

At week 12, 50.6% of patients who had received 40 mg of adalimumab weekly had achieved treatment response, compared with 26.8% of the placebo group (P < .001), with no new or unexpected adverse events, said Dr. Kimball. The weekly 40-mg dose also beat placebo in subgroups stratified by smoking status, sex, disease duration, disease severity, and age, she said. Adalimumab outperformed placebo for patients of black race or who had a body mass index (BMI) of at least 40 kg/m², although the differences did not reach statistical significance. Treated patients also had 23% fewer flares (defined as a 25% increase in lesion count; P = .001), and 18.9 average days of flare, compared with 32 days for the placebo group (P = .001), Dr. Kimball reported.

Past studies have linked adalimumab to serious systemic infections, demyelinating disorders, and lymphoma and other malignancies. No patients in the PIONEER trials developed these adverse events except for nonmelanoma skin cancer, said Dr. Kimball. In all, 2% of patients in each arm developed adverse events that led them to stop treatment, she added. Rates of infection were similar among the treatment groups. Although one patient (1%) on 40 mg weekly for 36 weeks developed pneumonia, none of the patients in the other arms developed serious infections.

Abbvie is the manufacturer of adalimumab and sponsored the trials. Dr. Kimball reported receiving consulting honoraria and research grants from Abbvie and several other pharmaceutical companies.

SAN FRANCISCO – Weekly treatment with 40 mg of adalimumab yielded the strongest clinical responses in adults with moderate to severe hidradenitis suppurativa with a safety profile similar to less intensive doses, according to data from two phase III trials.

Overall, 43% of adalimumab-treated patients achieved the predefined clinical response at 36 weeks, compared with 28% of patients who first received adalimumab and switched to placebo, Dr. Alexa Kimball said at the annual meeting of the American Academy of Dermatology. The 40-mg weekly dose also beat placebo in demographic subgroup analyses, said Dr. Kimball, professor of dermatology at Harvard Medical School in Boston. “Greater responses rates with this dose, combined with no difference in safety across the three treatment arms, suggests that weekly dosing was the optimal medium-term dosing strategy in hidradenitis suppurativa,” she added.

Hidradenitis suppurativa (also called acne inversa) is a chronic follicular occlusive skin disease that affects about 1%-4% of adults, particularly women, smokers, and obese or overweight patients. The disease has very few treatment options. Patients can develop recurrent abscesses, draining sinuses, and scarring, all of which negatively affect quality of life.

Adalimumab is an anti–tumor necrosis factor–alpha agent that previously bested placebo for hidradenitis suppurativa in phase II trials. Dr. Kimball and associates analyzed data on 633 patients with moderate to severe disease from two phase III, placebo-controlled trials (PIONEER I and II). For the first 12 weeks, patients were randomized to placebo or to 40 mg of adalimumab weekly. At week 12, patients were rerandomized to 40 mg adalimumab weekly, 40 mg of adalimumab every other week, or to placebo. The researchers defined treatment response as at least a 50% drop in abscesses and inflammatory nodules, with no numerical increase in individual numbers of abscesses or draining fistulas.

At week 12, 50.6% of patients who had received 40 mg of adalimumab weekly had achieved treatment response, compared with 26.8% of the placebo group (P < .001), with no new or unexpected adverse events, said Dr. Kimball. The weekly 40-mg dose also beat placebo in subgroups stratified by smoking status, sex, disease duration, disease severity, and age, she said. Adalimumab outperformed placebo for patients of black race or who had a body mass index (BMI) of at least 40 kg/m², although the differences did not reach statistical significance. Treated patients also had 23% fewer flares (defined as a 25% increase in lesion count; P = .001), and 18.9 average days of flare, compared with 32 days for the placebo group (P = .001), Dr. Kimball reported.

Past studies have linked adalimumab to serious systemic infections, demyelinating disorders, and lymphoma and other malignancies. No patients in the PIONEER trials developed these adverse events except for nonmelanoma skin cancer, said Dr. Kimball. In all, 2% of patients in each arm developed adverse events that led them to stop treatment, she added. Rates of infection were similar among the treatment groups. Although one patient (1%) on 40 mg weekly for 36 weeks developed pneumonia, none of the patients in the other arms developed serious infections.

Abbvie is the manufacturer of adalimumab and sponsored the trials. Dr. Kimball reported receiving consulting honoraria and research grants from Abbvie and several other pharmaceutical companies.

SAN FRANCISCO – Weekly treatment with 40 mg of adalimumab yielded the strongest clinical responses in adults with moderate to severe hidradenitis suppurativa with a safety profile similar to less intensive doses, according to data from two phase III trials.

Overall, 43% of adalimumab-treated patients achieved the predefined clinical response at 36 weeks, compared with 28% of patients who first received adalimumab and switched to placebo, Dr. Alexa Kimball said at the annual meeting of the American Academy of Dermatology. The 40-mg weekly dose also beat placebo in demographic subgroup analyses, said Dr. Kimball, professor of dermatology at Harvard Medical School in Boston. “Greater responses rates with this dose, combined with no difference in safety across the three treatment arms, suggests that weekly dosing was the optimal medium-term dosing strategy in hidradenitis suppurativa,” she added.

Hidradenitis suppurativa (also called acne inversa) is a chronic follicular occlusive skin disease that affects about 1%-4% of adults, particularly women, smokers, and obese or overweight patients. The disease has very few treatment options. Patients can develop recurrent abscesses, draining sinuses, and scarring, all of which negatively affect quality of life.

Adalimumab is an anti–tumor necrosis factor–alpha agent that previously bested placebo for hidradenitis suppurativa in phase II trials. Dr. Kimball and associates analyzed data on 633 patients with moderate to severe disease from two phase III, placebo-controlled trials (PIONEER I and II). For the first 12 weeks, patients were randomized to placebo or to 40 mg of adalimumab weekly. At week 12, patients were rerandomized to 40 mg adalimumab weekly, 40 mg of adalimumab every other week, or to placebo. The researchers defined treatment response as at least a 50% drop in abscesses and inflammatory nodules, with no numerical increase in individual numbers of abscesses or draining fistulas.

At week 12, 50.6% of patients who had received 40 mg of adalimumab weekly had achieved treatment response, compared with 26.8% of the placebo group (P < .001), with no new or unexpected adverse events, said Dr. Kimball. The weekly 40-mg dose also beat placebo in subgroups stratified by smoking status, sex, disease duration, disease severity, and age, she said. Adalimumab outperformed placebo for patients of black race or who had a body mass index (BMI) of at least 40 kg/m², although the differences did not reach statistical significance. Treated patients also had 23% fewer flares (defined as a 25% increase in lesion count; P = .001), and 18.9 average days of flare, compared with 32 days for the placebo group (P = .001), Dr. Kimball reported.

Past studies have linked adalimumab to serious systemic infections, demyelinating disorders, and lymphoma and other malignancies. No patients in the PIONEER trials developed these adverse events except for nonmelanoma skin cancer, said Dr. Kimball. In all, 2% of patients in each arm developed adverse events that led them to stop treatment, she added. Rates of infection were similar among the treatment groups. Although one patient (1%) on 40 mg weekly for 36 weeks developed pneumonia, none of the patients in the other arms developed serious infections.

Abbvie is the manufacturer of adalimumab and sponsored the trials. Dr. Kimball reported receiving consulting honoraria and research grants from Abbvie and several other pharmaceutical companies.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Four gene loci in patients with Crohn’s disease were significantly linked with phenotypic traits such as erythema nodosum or having a complicated or mild course of disease, researchers reported in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.12.030).

The work is the first genome-wide study to link specific genetic loci with clinically relevant traits in patients with Crohn’s disease (CD), said Dr. Arnald Alonso at the Vall d’Hebron Research Institute and the University of Catalonia in Barcelona and his associates. “Importantly, these new loci have not been previously described as risk factors for CD,” the researchers said. “Our results therefore demonstrate the existence of a genetic component for disease heterogeneity that is independent of the genetic variation associated with the susceptibility to Crohn’s disease.”

Crohn’s disease varies greatly in terms of severity, location of pathology, complications, and other factors. Genome-wide association studies have linked 140 genetic “risk loci” with susceptibility to CD, but past work has only found one gene locus (NOD2) that is definitively linked a single clinical trait of CD (ileal pathology), the investigators noted. For their genome-wide association study, they genotyped 576,818 single nucleotide polymorphisms in a discovery cohort of 1,090 CD patients of European ancestry who presented at university hospitals in Spain between 2007 and 2010, as well as 1,493 healthy controls. They examined associations between these genetic markers and 17 characteristics (or phenotypes) of CD related to disease location, disease behavior and course, age at onset, and extra-intestinal manifestations of CD. Next, the investigators studied a separate “replication” cohort of 1,296 CD patients in order to assess the 57 markers that had been most strongly associated (P < .0002) with CD phenotypes among the discovery cohort (Gastroenterology, http://www.gastrojournal.org/article/S0016-5085(14)01582-0/abstract).

These combined analyses showed that clinical phenotypes in CD were most significantly linked with four markers, including MAGI1, CLCA2, 2q24.1, and LY75, reported the investigators. The MAGI1 gene was found to predict complicated structuring disease course and stricturing behavior in CD, although it did not appear to speed its onset, they said. The gene encodes proteins that have been found to play an important role in the tight junctions between epithelial cells, and consequently in intestinal barrier function, they noted, adding that disruption of that mucosal integrity contributes to the pathogenesis of ulcerative colitis and CD. “Importantly, an increased intestinal permeability has been described in patients with active CD as well as in their first-degree relatives,” they added. “This evidence strongly suggests that increased intestinal permeability is not only a consequence of intestinal inflammation occurring in CD patients, but it is rather a risk factor for CD.”

The other three loci that were significantly associated with CD traits predicted ileal involvement (CLCA2), erythema nodosum (LY75), and having a mild disease course (2q24.1), the researchers reported. Taken together, the findings “indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease,” concluded Dr. Alonso and his associates. “Further functional studies of these new loci will provide a better understanding of the biological mechanisms that are involved in the development of these relevant clinical phenotypes.”

The Spanish Ministry of Economy and Competitiveness funded the study. The investigators reported having no relevant financial disclosures.

Two-thirds of endoscopists met national quality benchmarks for detecting colonic adenomas, but detection rates varied eightfold among male patients and 27-fold among female patients, according to a retrospective community-based cohort study.

These ranges narrowed somewhat when researchers controlled for patient-specific factors, such as age and sex, said Dr. Christopher Jensen and his associates at Kaiser Permanente Division of Research in Oakland, Calif. But researchers found that adjusting for those variables had little effect on how endoscopists ranked in terms of adenoma detection rates (ADRs) compared with their peers. Based on those findings, evaluators probably only need to account for patient demographics when comparing ADRs for endoscopists who tend to see very distinct types of patients, the investigators wrote in the April issue of Clinical Gastroenterology and Hepatology 2014 Oct 25. (doi:10.1016/j.cgh.2014.10.020).

Colorectal cancer remains the second leading cause of cancer mortality in the United States, and prevention hinges on detecting and removing precancerous adenomatous polyps of the colon. For this reason, organizations such as the U.S. Multi-Society Task Force on Colorectal Cancer and the U.S. Centers for Medicaid and Medicare Services have recommended benchmark ADRs of at least 25% for male patients and 15% for female patients. Although some studies have examined how characteristics of physicians and their practices affect ADRs, none have previously assessed effects of patient-specific variables, Dr. Jensen and his associates said (Clin. Gastroenterol. Hepatol. http://www.ncbi.nlm.nih.gov/pubmed/25445767.

The investigators retrospectively studied 108,662 colonoscopies and 20,792 screening colonoscopies carried out by 102 endoscopists at Kaiser Permanente Northern California between 2006 and 2008. They calculated ADRs for each physician before and after they adjusted for the patients’ age, sex, race/ethnicity, and family history of colorectal cancer.

In all, 67% of examiners met the gastrointestinal society guidelines for ADRs in male patients, and 68% met guidelines for female patients, the researchers found. But ADRs among the examiners ranged widely – from 7.7% to 61.5% for male patients and from 1.7% to 45.6% for females, the investigators said. Adjustments for patient demographics and family history of colorectal cancer cut the variation from 8-fold down to 3-fold for male patients, and from 27-fold to 5-fold for females. However, physicians’ absolute rankings among their peers remained similar before and after controlling for patient case mix. “Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection,” concluded Dr. Jensen and his associates. “The findings raise the question of whether adenoma detection rates should routinely be adjusted for case mix,” they added. “The need for adjustment will likely depend on the degree of variation between physicians in patient case mix, and how rates are used as a performance metric. Adjusted rates would likely only be needed in settings where physicians had very different patient demographics relative to sex and age.”

The study was funded by the Kaiser Permanente Community Benefits program, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported having no relevant financial disclosures.

Two-thirds of endoscopists met national quality benchmarks for detecting colonic adenomas, but detection rates varied eightfold among male patients and 27-fold among female patients, according to a retrospective community-based cohort study.

These ranges narrowed somewhat when researchers controlled for patient-specific factors, such as age and sex, said Dr. Christopher Jensen and his associates at Kaiser Permanente Division of Research in Oakland, Calif. But researchers found that adjusting for those variables had little effect on how endoscopists ranked in terms of adenoma detection rates (ADRs) compared with their peers. Based on those findings, evaluators probably only need to account for patient demographics when comparing ADRs for endoscopists who tend to see very distinct types of patients, the investigators wrote in the April issue of Clinical Gastroenterology and Hepatology 2014 Oct 25. (doi:10.1016/j.cgh.2014.10.020).

Colorectal cancer remains the second leading cause of cancer mortality in the United States, and prevention hinges on detecting and removing precancerous adenomatous polyps of the colon. For this reason, organizations such as the U.S. Multi-Society Task Force on Colorectal Cancer and the U.S. Centers for Medicaid and Medicare Services have recommended benchmark ADRs of at least 25% for male patients and 15% for female patients. Although some studies have examined how characteristics of physicians and their practices affect ADRs, none have previously assessed effects of patient-specific variables, Dr. Jensen and his associates said (Clin. Gastroenterol. Hepatol. http://www.ncbi.nlm.nih.gov/pubmed/25445767.

The investigators retrospectively studied 108,662 colonoscopies and 20,792 screening colonoscopies carried out by 102 endoscopists at Kaiser Permanente Northern California between 2006 and 2008. They calculated ADRs for each physician before and after they adjusted for the patients’ age, sex, race/ethnicity, and family history of colorectal cancer.

In all, 67% of examiners met the gastrointestinal society guidelines for ADRs in male patients, and 68% met guidelines for female patients, the researchers found. But ADRs among the examiners ranged widely – from 7.7% to 61.5% for male patients and from 1.7% to 45.6% for females, the investigators said. Adjustments for patient demographics and family history of colorectal cancer cut the variation from 8-fold down to 3-fold for male patients, and from 27-fold to 5-fold for females. However, physicians’ absolute rankings among their peers remained similar before and after controlling for patient case mix. “Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection,” concluded Dr. Jensen and his associates. “The findings raise the question of whether adenoma detection rates should routinely be adjusted for case mix,” they added. “The need for adjustment will likely depend on the degree of variation between physicians in patient case mix, and how rates are used as a performance metric. Adjusted rates would likely only be needed in settings where physicians had very different patient demographics relative to sex and age.”

The study was funded by the Kaiser Permanente Community Benefits program, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported having no relevant financial disclosures.

Two-thirds of endoscopists met national quality benchmarks for detecting colonic adenomas, but detection rates varied eightfold among male patients and 27-fold among female patients, according to a retrospective community-based cohort study.

These ranges narrowed somewhat when researchers controlled for patient-specific factors, such as age and sex, said Dr. Christopher Jensen and his associates at Kaiser Permanente Division of Research in Oakland, Calif. But researchers found that adjusting for those variables had little effect on how endoscopists ranked in terms of adenoma detection rates (ADRs) compared with their peers. Based on those findings, evaluators probably only need to account for patient demographics when comparing ADRs for endoscopists who tend to see very distinct types of patients, the investigators wrote in the April issue of Clinical Gastroenterology and Hepatology 2014 Oct 25. (doi:10.1016/j.cgh.2014.10.020).

Colorectal cancer remains the second leading cause of cancer mortality in the United States, and prevention hinges on detecting and removing precancerous adenomatous polyps of the colon. For this reason, organizations such as the U.S. Multi-Society Task Force on Colorectal Cancer and the U.S. Centers for Medicaid and Medicare Services have recommended benchmark ADRs of at least 25% for male patients and 15% for female patients. Although some studies have examined how characteristics of physicians and their practices affect ADRs, none have previously assessed effects of patient-specific variables, Dr. Jensen and his associates said (Clin. Gastroenterol. Hepatol. http://www.ncbi.nlm.nih.gov/pubmed/25445767.

The investigators retrospectively studied 108,662 colonoscopies and 20,792 screening colonoscopies carried out by 102 endoscopists at Kaiser Permanente Northern California between 2006 and 2008. They calculated ADRs for each physician before and after they adjusted for the patients’ age, sex, race/ethnicity, and family history of colorectal cancer.

In all, 67% of examiners met the gastrointestinal society guidelines for ADRs in male patients, and 68% met guidelines for female patients, the researchers found. But ADRs among the examiners ranged widely – from 7.7% to 61.5% for male patients and from 1.7% to 45.6% for females, the investigators said. Adjustments for patient demographics and family history of colorectal cancer cut the variation from 8-fold down to 3-fold for male patients, and from 27-fold to 5-fold for females. However, physicians’ absolute rankings among their peers remained similar before and after controlling for patient case mix. “Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection,” concluded Dr. Jensen and his associates. “The findings raise the question of whether adenoma detection rates should routinely be adjusted for case mix,” they added. “The need for adjustment will likely depend on the degree of variation between physicians in patient case mix, and how rates are used as a performance metric. Adjusted rates would likely only be needed in settings where physicians had very different patient demographics relative to sex and age.”

The study was funded by the Kaiser Permanente Community Benefits program, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported having no relevant financial disclosures.