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JAK inhibitor improves alopecia, with caveats
SCOTTSDALE, ARIZ. – The Janus kinase (JAK) inhibitor tofacitinib dramatically improved several cases of alopecia areata (AA), although some patients relapsed to worse than baseline after completing treatment in a small open label pilot trial.
“Regrowth was demonstrated in 11 out of 12 patients on tofacitinib. Seven out of 12 patients achieved more than 50% regrowth,” Dr. Shawn Sidharthan reported at the annual meeting of the Society for Investigative Dermatology.
Worldwide, alopecia areata, which is caused by immune-mediated destruction of hair follicles, has a lifetime incidence of about 2% (Clin Cosmet Investig Dermatol. 2015;8:397-403). But there are no Food and Drug Administration–approved treatments for AA. Tofacitinib (Xeljanz), which is approved by the FDA for moderate to severe rheumatoid arthritis in adults, is a JAK1 and JAK3 inhibitor that curbs the interferon-gamma response inflammatory pathway, said Dr. Sidharthan of the department of dermatology and genetics at Columbia University, New York.
AA shares the same interferon response pathway, and tofacitinib prevented alopecia in mice and led to hair regrowth in a patient with alopecia universalis, he noted.
The single-arm trial included seven patients with moderate to severe patchy AA and five patients with alopecia totalis or alopecia universalis. Patients were treated for 6 months. They initially received 5 mg tofacitinib orally twice daily, which was increased to 10 mg twice daily to improve response. The investigators evaluated patients based on SALT (Severity of Alopecia Tool) scores and the Alopecia Areata Disease Activity Index (ALADIN), which uses three-dimensional bioinformatics to identify groups of genes linked to alopecia.
Seven of 12 patients experienced at least 50% regrowth, including six patients who only improved on 10 mg tofacitinib twice daily, Dr. Sidharthan said. Three additional patients “had good regrowth, but not 50%,” he reported. Among the two remaining patients, one had full regrowth, but dropped out of the study because of uncontrolled hypertension, and one patient with alopecia universalis had little or no regrowth.
Notably, two patients began shedding hair after stopping tofacitinib during the observation period of the study, and their final SALT scores were worse than baseline, Dr. Sidharthan said.
Laboratory monitoring of the cohort revealed no severe adverse events, but one patient paused treatment because of thrombocytopenia. The patient’s platelet count normalized after 2 weeks off tofacitinib, and remained normal when the dose was gradually increased to 10 mg twice daily. Another patient developed leukocytosis that resolved during the off-treatment observation period. One patient who did not comply with instructions to avoid alcohol had elevated liver function tests and was taken off the study. Two patients experienced self-limiting diarrhea, and one patient developed trace hematuria, Dr. Sidharthan noted.
In the study, ALADIN scores correlated with clinical response, he said.
He and his coinvestigators concluded that the overall results “provide a strong rationale for larger clinical trials using JAK inhibitors in alopecia areata,” he said.
Dr. Sidharthan noted that another oral JAK inhibitor, ruxolitinib (Jakafi), led to nearly full hair regrowth in three patients with alopecia in a Columbia University study (Nat Med. 2014 Sep; 20[9]:1043-9).
The Locks of Love Foundation funded the research. Dr. Sidharthan, a clinical research fellow in dermatology at Columbia, had no disclosures.
SCOTTSDALE, ARIZ. – The Janus kinase (JAK) inhibitor tofacitinib dramatically improved several cases of alopecia areata (AA), although some patients relapsed to worse than baseline after completing treatment in a small open label pilot trial.
“Regrowth was demonstrated in 11 out of 12 patients on tofacitinib. Seven out of 12 patients achieved more than 50% regrowth,” Dr. Shawn Sidharthan reported at the annual meeting of the Society for Investigative Dermatology.
Worldwide, alopecia areata, which is caused by immune-mediated destruction of hair follicles, has a lifetime incidence of about 2% (Clin Cosmet Investig Dermatol. 2015;8:397-403). But there are no Food and Drug Administration–approved treatments for AA. Tofacitinib (Xeljanz), which is approved by the FDA for moderate to severe rheumatoid arthritis in adults, is a JAK1 and JAK3 inhibitor that curbs the interferon-gamma response inflammatory pathway, said Dr. Sidharthan of the department of dermatology and genetics at Columbia University, New York.
AA shares the same interferon response pathway, and tofacitinib prevented alopecia in mice and led to hair regrowth in a patient with alopecia universalis, he noted.
The single-arm trial included seven patients with moderate to severe patchy AA and five patients with alopecia totalis or alopecia universalis. Patients were treated for 6 months. They initially received 5 mg tofacitinib orally twice daily, which was increased to 10 mg twice daily to improve response. The investigators evaluated patients based on SALT (Severity of Alopecia Tool) scores and the Alopecia Areata Disease Activity Index (ALADIN), which uses three-dimensional bioinformatics to identify groups of genes linked to alopecia.
Seven of 12 patients experienced at least 50% regrowth, including six patients who only improved on 10 mg tofacitinib twice daily, Dr. Sidharthan said. Three additional patients “had good regrowth, but not 50%,” he reported. Among the two remaining patients, one had full regrowth, but dropped out of the study because of uncontrolled hypertension, and one patient with alopecia universalis had little or no regrowth.
Notably, two patients began shedding hair after stopping tofacitinib during the observation period of the study, and their final SALT scores were worse than baseline, Dr. Sidharthan said.
Laboratory monitoring of the cohort revealed no severe adverse events, but one patient paused treatment because of thrombocytopenia. The patient’s platelet count normalized after 2 weeks off tofacitinib, and remained normal when the dose was gradually increased to 10 mg twice daily. Another patient developed leukocytosis that resolved during the off-treatment observation period. One patient who did not comply with instructions to avoid alcohol had elevated liver function tests and was taken off the study. Two patients experienced self-limiting diarrhea, and one patient developed trace hematuria, Dr. Sidharthan noted.
In the study, ALADIN scores correlated with clinical response, he said.
He and his coinvestigators concluded that the overall results “provide a strong rationale for larger clinical trials using JAK inhibitors in alopecia areata,” he said.
Dr. Sidharthan noted that another oral JAK inhibitor, ruxolitinib (Jakafi), led to nearly full hair regrowth in three patients with alopecia in a Columbia University study (Nat Med. 2014 Sep; 20[9]:1043-9).
The Locks of Love Foundation funded the research. Dr. Sidharthan, a clinical research fellow in dermatology at Columbia, had no disclosures.
SCOTTSDALE, ARIZ. – The Janus kinase (JAK) inhibitor tofacitinib dramatically improved several cases of alopecia areata (AA), although some patients relapsed to worse than baseline after completing treatment in a small open label pilot trial.
“Regrowth was demonstrated in 11 out of 12 patients on tofacitinib. Seven out of 12 patients achieved more than 50% regrowth,” Dr. Shawn Sidharthan reported at the annual meeting of the Society for Investigative Dermatology.
Worldwide, alopecia areata, which is caused by immune-mediated destruction of hair follicles, has a lifetime incidence of about 2% (Clin Cosmet Investig Dermatol. 2015;8:397-403). But there are no Food and Drug Administration–approved treatments for AA. Tofacitinib (Xeljanz), which is approved by the FDA for moderate to severe rheumatoid arthritis in adults, is a JAK1 and JAK3 inhibitor that curbs the interferon-gamma response inflammatory pathway, said Dr. Sidharthan of the department of dermatology and genetics at Columbia University, New York.
AA shares the same interferon response pathway, and tofacitinib prevented alopecia in mice and led to hair regrowth in a patient with alopecia universalis, he noted.
The single-arm trial included seven patients with moderate to severe patchy AA and five patients with alopecia totalis or alopecia universalis. Patients were treated for 6 months. They initially received 5 mg tofacitinib orally twice daily, which was increased to 10 mg twice daily to improve response. The investigators evaluated patients based on SALT (Severity of Alopecia Tool) scores and the Alopecia Areata Disease Activity Index (ALADIN), which uses three-dimensional bioinformatics to identify groups of genes linked to alopecia.
Seven of 12 patients experienced at least 50% regrowth, including six patients who only improved on 10 mg tofacitinib twice daily, Dr. Sidharthan said. Three additional patients “had good regrowth, but not 50%,” he reported. Among the two remaining patients, one had full regrowth, but dropped out of the study because of uncontrolled hypertension, and one patient with alopecia universalis had little or no regrowth.
Notably, two patients began shedding hair after stopping tofacitinib during the observation period of the study, and their final SALT scores were worse than baseline, Dr. Sidharthan said.
Laboratory monitoring of the cohort revealed no severe adverse events, but one patient paused treatment because of thrombocytopenia. The patient’s platelet count normalized after 2 weeks off tofacitinib, and remained normal when the dose was gradually increased to 10 mg twice daily. Another patient developed leukocytosis that resolved during the off-treatment observation period. One patient who did not comply with instructions to avoid alcohol had elevated liver function tests and was taken off the study. Two patients experienced self-limiting diarrhea, and one patient developed trace hematuria, Dr. Sidharthan noted.
In the study, ALADIN scores correlated with clinical response, he said.
He and his coinvestigators concluded that the overall results “provide a strong rationale for larger clinical trials using JAK inhibitors in alopecia areata,” he said.
Dr. Sidharthan noted that another oral JAK inhibitor, ruxolitinib (Jakafi), led to nearly full hair regrowth in three patients with alopecia in a Columbia University study (Nat Med. 2014 Sep; 20[9]:1043-9).
The Locks of Love Foundation funded the research. Dr. Sidharthan, a clinical research fellow in dermatology at Columbia, had no disclosures.
AT THE 2016 SID ANNUAL MEETING
Key clinical point: Tofacitinib dramatically improved several cases of alopecia areata, but some patients relapsed after stopping treatment.
Major finding: Eleven of 12 patients experienced regrowth, including seven with at least 50% regrowth, but two patients relapsed to worse than baseline after stopping treatment.
Data source: The single-center open-label pilot trial evaluated tofacitinib in 12 patients with alopecia areata, totalis, or universalis.
Disclosures: The Locks of Love Foundation funded the research. Dr. Shawn Sidharthan had no disclosures.
Adolescent obesity rose slightly, again
Nearly one in five young people in the United States are obese, and proportionally more adolescents have been obese during every time period measured since 1994, according to an analysis published online June 7 in JAMA.
But the most recent data suggest only a “small” rise in adolescent obesity since 2011, and stable rates among children during this time period, said Cynthia L. Ogden, Ph.D., of the National Center for Health Statistics at the Centers for Disease Control and Prevention.
Few studies of obesity in young people have teased out rates by age, according to Dr. Ogden and her associates. Using National Health and Nutrition Examination Survey data, they calculated rates of obesity and extreme obesity among 40,780 children and adolescents aged 2-19 years for the periods 1988-1994 through 2013-2014. They defined obesity as a body mass index (BMI) at or above the sex-specific 95th percentile on the CDC BMI-for-age growth charts, and they defined extreme obesity as a BMI at least 120% of the sex-specific 95th percentile on the charts (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6361).
Based on these definitions, 17% of children and adolescents were obese between 2011 and 2014, while 6% were extremely obese, the investigators reported. Furthermore, 21% of adolescents were obese in 2013-2014, compared with 17% during 2003-2004 and 11% during 1988-1994.
Rates for 6- to -11-year-olds have remained fairly stable in the high teens for more than a decade, while rates among 2- to 5-year-olds peaked in 2003-2004 at nearly 14% before dropping to about 9% during 2013-2014. The prevalence of obesity varied little by sex, but diverged substantially by race and ethnicity. For example, in 2011-2014, 23% of Hispanics and about 23% of black children were obese, and 9% and 12% were extremely obese, respectively the researchers reported. Rates for the same ages of non-Hispanic Asian children were 9% and 2%, respectively, and those for non-Hispanic whites were 20% and 7%, respectively.
“Body mass index is an imperfect measure of body fat and health risk,” the investigators cautioned. “There are racial and ethnic differences in body fat at the same BMI level. Among children and adolescents, the definition of obesity is statistical. Children and adolescents are compared with a group of U.S. children in the 1960s to early 1990s, so the prevalence of obesity is dependent on the characteristics of the age-specific population during that period. In addition, among young children, small changes in weight can lead to relatively large changes in BMI percentile”
The researchers reported no funding sources and had no disclosures.
Numerous foundations, industries, professional societies, and governmental agencies have provided hundreds of millions of dollars in funding to support basic science research in obesity, clinical trials, and observational studies, development of new drugs and devices, and hospital and community programs to help stem the tide of the obesity epidemic. In addition, communities, schools, places of worship, and professional societies have become active in attempting to counteract obesity – emphasizing exercise, better dietary choices, and nutritional labeling of foods.
Although it is impossible to know what the extent of the obesity epidemic would have been without these efforts, [these data] certainly do not suggest much success. Perhaps new incentives are needed to encourage the food industry to work with families and the medical community to prevent obesity. The stakes for the health of people in the United States are high, and creative solutions are needed.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are excerpted from their accompanying editorial (JAMA. 2016 Jun. doi: 10.1001/jama.2016.6190).
Numerous foundations, industries, professional societies, and governmental agencies have provided hundreds of millions of dollars in funding to support basic science research in obesity, clinical trials, and observational studies, development of new drugs and devices, and hospital and community programs to help stem the tide of the obesity epidemic. In addition, communities, schools, places of worship, and professional societies have become active in attempting to counteract obesity – emphasizing exercise, better dietary choices, and nutritional labeling of foods.
Although it is impossible to know what the extent of the obesity epidemic would have been without these efforts, [these data] certainly do not suggest much success. Perhaps new incentives are needed to encourage the food industry to work with families and the medical community to prevent obesity. The stakes for the health of people in the United States are high, and creative solutions are needed.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are excerpted from their accompanying editorial (JAMA. 2016 Jun. doi: 10.1001/jama.2016.6190).
Numerous foundations, industries, professional societies, and governmental agencies have provided hundreds of millions of dollars in funding to support basic science research in obesity, clinical trials, and observational studies, development of new drugs and devices, and hospital and community programs to help stem the tide of the obesity epidemic. In addition, communities, schools, places of worship, and professional societies have become active in attempting to counteract obesity – emphasizing exercise, better dietary choices, and nutritional labeling of foods.
Although it is impossible to know what the extent of the obesity epidemic would have been without these efforts, [these data] certainly do not suggest much success. Perhaps new incentives are needed to encourage the food industry to work with families and the medical community to prevent obesity. The stakes for the health of people in the United States are high, and creative solutions are needed.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are excerpted from their accompanying editorial (JAMA. 2016 Jun. doi: 10.1001/jama.2016.6190).
Nearly one in five young people in the United States are obese, and proportionally more adolescents have been obese during every time period measured since 1994, according to an analysis published online June 7 in JAMA.
But the most recent data suggest only a “small” rise in adolescent obesity since 2011, and stable rates among children during this time period, said Cynthia L. Ogden, Ph.D., of the National Center for Health Statistics at the Centers for Disease Control and Prevention.
Few studies of obesity in young people have teased out rates by age, according to Dr. Ogden and her associates. Using National Health and Nutrition Examination Survey data, they calculated rates of obesity and extreme obesity among 40,780 children and adolescents aged 2-19 years for the periods 1988-1994 through 2013-2014. They defined obesity as a body mass index (BMI) at or above the sex-specific 95th percentile on the CDC BMI-for-age growth charts, and they defined extreme obesity as a BMI at least 120% of the sex-specific 95th percentile on the charts (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6361).
Based on these definitions, 17% of children and adolescents were obese between 2011 and 2014, while 6% were extremely obese, the investigators reported. Furthermore, 21% of adolescents were obese in 2013-2014, compared with 17% during 2003-2004 and 11% during 1988-1994.
Rates for 6- to -11-year-olds have remained fairly stable in the high teens for more than a decade, while rates among 2- to 5-year-olds peaked in 2003-2004 at nearly 14% before dropping to about 9% during 2013-2014. The prevalence of obesity varied little by sex, but diverged substantially by race and ethnicity. For example, in 2011-2014, 23% of Hispanics and about 23% of black children were obese, and 9% and 12% were extremely obese, respectively the researchers reported. Rates for the same ages of non-Hispanic Asian children were 9% and 2%, respectively, and those for non-Hispanic whites were 20% and 7%, respectively.
“Body mass index is an imperfect measure of body fat and health risk,” the investigators cautioned. “There are racial and ethnic differences in body fat at the same BMI level. Among children and adolescents, the definition of obesity is statistical. Children and adolescents are compared with a group of U.S. children in the 1960s to early 1990s, so the prevalence of obesity is dependent on the characteristics of the age-specific population during that period. In addition, among young children, small changes in weight can lead to relatively large changes in BMI percentile”
The researchers reported no funding sources and had no disclosures.
Nearly one in five young people in the United States are obese, and proportionally more adolescents have been obese during every time period measured since 1994, according to an analysis published online June 7 in JAMA.
But the most recent data suggest only a “small” rise in adolescent obesity since 2011, and stable rates among children during this time period, said Cynthia L. Ogden, Ph.D., of the National Center for Health Statistics at the Centers for Disease Control and Prevention.
Few studies of obesity in young people have teased out rates by age, according to Dr. Ogden and her associates. Using National Health and Nutrition Examination Survey data, they calculated rates of obesity and extreme obesity among 40,780 children and adolescents aged 2-19 years for the periods 1988-1994 through 2013-2014. They defined obesity as a body mass index (BMI) at or above the sex-specific 95th percentile on the CDC BMI-for-age growth charts, and they defined extreme obesity as a BMI at least 120% of the sex-specific 95th percentile on the charts (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6361).
Based on these definitions, 17% of children and adolescents were obese between 2011 and 2014, while 6% were extremely obese, the investigators reported. Furthermore, 21% of adolescents were obese in 2013-2014, compared with 17% during 2003-2004 and 11% during 1988-1994.
Rates for 6- to -11-year-olds have remained fairly stable in the high teens for more than a decade, while rates among 2- to 5-year-olds peaked in 2003-2004 at nearly 14% before dropping to about 9% during 2013-2014. The prevalence of obesity varied little by sex, but diverged substantially by race and ethnicity. For example, in 2011-2014, 23% of Hispanics and about 23% of black children were obese, and 9% and 12% were extremely obese, respectively the researchers reported. Rates for the same ages of non-Hispanic Asian children were 9% and 2%, respectively, and those for non-Hispanic whites were 20% and 7%, respectively.
“Body mass index is an imperfect measure of body fat and health risk,” the investigators cautioned. “There are racial and ethnic differences in body fat at the same BMI level. Among children and adolescents, the definition of obesity is statistical. Children and adolescents are compared with a group of U.S. children in the 1960s to early 1990s, so the prevalence of obesity is dependent on the characteristics of the age-specific population during that period. In addition, among young children, small changes in weight can lead to relatively large changes in BMI percentile”
The researchers reported no funding sources and had no disclosures.
FROM JAMA
Key clinical point:Nearly one in five children and adolescents are obese, and rates of adolescent obesity have risen during every time period measured since 1994.
Major finding: About 17% of children and adolescents in the United States were obese between 2011 and 2014 (95% confidence interval, 15.5%-18.6%). Nearly 21% of adolescents were obese in 2013-2014, compared with 17% during 2003-2004 and 10% during 1988-1994.
Data source: An analysis of the body mass indexes of 40,780 individuals aged 2-19 years from the National Health and Nutrition Examination Survey.
Disclosures: The researchers reported no funding sources and had no disclosures.
Obesity continues to trend up among women over the past decade
Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m2, and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.
In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.
Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m2) and class 3 obesity (BMI greater than 40 kg/m2) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).
About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.
During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.
Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.
The investigators reported no funding sources and had no disclosures.
Much research and attention have been directed toward the treatment of obesity, but the development of new drugs and procedures will not solve the problem. Perhaps genetics will unlock some of the mysteries of obesity, but this will take time, and more immediate solutions are needed. The emphasis has to be on prevention, despite evidence that school- and community-based prevention programs and education campaigns by local governments and professional societies have not been highly successful.
The obesity epidemic in the United States is now 3 decades old, and huge investments have been made in research, clinical care, and development of various programs to counteract obesity. However, few data suggest the epidemic is diminishing. Perhaps it is time for an entirely different approach, one that emphasizes collaboration with the food and restaurant industries that are in part responsible for putting food on our dinner tables.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are from their accompanying editorial (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6190).
Much research and attention have been directed toward the treatment of obesity, but the development of new drugs and procedures will not solve the problem. Perhaps genetics will unlock some of the mysteries of obesity, but this will take time, and more immediate solutions are needed. The emphasis has to be on prevention, despite evidence that school- and community-based prevention programs and education campaigns by local governments and professional societies have not been highly successful.
The obesity epidemic in the United States is now 3 decades old, and huge investments have been made in research, clinical care, and development of various programs to counteract obesity. However, few data suggest the epidemic is diminishing. Perhaps it is time for an entirely different approach, one that emphasizes collaboration with the food and restaurant industries that are in part responsible for putting food on our dinner tables.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are from their accompanying editorial (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6190).
Much research and attention have been directed toward the treatment of obesity, but the development of new drugs and procedures will not solve the problem. Perhaps genetics will unlock some of the mysteries of obesity, but this will take time, and more immediate solutions are needed. The emphasis has to be on prevention, despite evidence that school- and community-based prevention programs and education campaigns by local governments and professional societies have not been highly successful.
The obesity epidemic in the United States is now 3 decades old, and huge investments have been made in research, clinical care, and development of various programs to counteract obesity. However, few data suggest the epidemic is diminishing. Perhaps it is time for an entirely different approach, one that emphasizes collaboration with the food and restaurant industries that are in part responsible for putting food on our dinner tables.
Dr. Jody W. Zylke is deputy editor of JAMA. Dr. Howard Bauchner is editor in chief of JAMA. These comments are from their accompanying editorial (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6190).
Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m2, and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.
In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.
Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m2) and class 3 obesity (BMI greater than 40 kg/m2) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).
About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.
During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.
Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.
The investigators reported no funding sources and had no disclosures.
Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m2, and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.
In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.
Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m2) and class 3 obesity (BMI greater than 40 kg/m2) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).
About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.
During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.
Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.
The investigators reported no funding sources and had no disclosures.
FROM JAMA
Key clinical point: Significantly more women in the United States are obese now than a decade ago, while obesity rates among men have leveled off.
Major finding: During 2005 through 2014, the adjusted prevalence of obesity among women rose from 35.6% to 41.1% (P = .004).
Data source: An analysis of the body mass index for 26,468 adults from the National Health and Nutrition Examination Survey.
Disclosures: The researchers reported no funding sources and had no disclosures.
Bezlotoxumab beats placebo at preventing recurrent C. difficile infections in high-risk patients
SAN DIEGO – Bezlotoxumab prevented recurrent Clostridium difficile infections (CDIs) among high-risk patients even more effectively than in the overall populations of the placebo-controlled MODIFY I and MODIFY II trials, according to a report at the annual Digestive Disease Week.
“In those key subpopulations at high risk for recurrence [of C. difficile infection], bezlotoxumab both reduced recurrence and increased rates of global cure,” said Dr. Ciaran P. Kelly of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. The biologic was especially effective among older adults and patients with at least one recent episode of CDI, Dr. Kelly and his associates found.
Bezlotoxumab is a monoclonal antibody targeting Clostridium difficile toxin B. The international, randomized, double-blind, 12-week MODIFY I and II trials included 2,656 patients with laboratory-confirmed CDI who were randomly assigned to receive either a single intravenous dose of the biologic (10 mg per kg) or placebo in addition to standard care antibiotics – that is, oral metronidazole and vancomycin; intravenous metronidazole with oral vancomycin; oral fidaxomicin; or oral fidaxomicin with intravenous metronidazole.
In both trials, bezlotoxumab was associated with a 10% decrease in rates of recurrent CDI, compared with placebo (P = .0003). Bezlotoxumab also achieved a 9.7% increase in rates of global cure, defined as clinical cure of the initial episode with no recurrence, Dr. Kelly said.
For the current analysis, he and his associates examined the efficacy of bezlotoxumab among patients at increased risk for recurrent CDI. These patients were older than 65 years, were immunocompromised, had a history of recurrent CDI, had been diagnosed with CDI within 6 months, and/or had severe CDI or were infected with hypervirulent, binary toxin positive strain. Most patients in the trials fell into at least one of these categories, Dr. Kelly said.
For each subgroup, bezlotoxumab was associated with lower rates of CDI recurrence and higher rates of global cure than in the overall study population, he emphasized. Compared with placebo, the most dramatic improvements in recurrence and global cure rates were among older patients (a 16% decrease and a 16% increase, respectively), patients with recent CDI (a 16% increase and a 12% decrease), patients with a history of recurrent CDI (a 13% decrease and a 12% increase) and immunocompromised patients (a 13% decrease and a 15% increase).
Neither trial generated a concerning safety signal, according to Dr. Kelly. There were “slight increases” in infusion reactions in the bezlotoxumab arms, but these were mostly minor and short lived, he added. “Serious adverse events were, in fact, slightly more common in the placebo group, mainly because of adverse events related to recurrence.”
The MODIFY trials were funded by Merck. Dr. Kelly reported consulting and advisory relationships with Merck, Sanofi Pasteur, Seres Therapeutics, Summit, and Alba.
SAN DIEGO – Bezlotoxumab prevented recurrent Clostridium difficile infections (CDIs) among high-risk patients even more effectively than in the overall populations of the placebo-controlled MODIFY I and MODIFY II trials, according to a report at the annual Digestive Disease Week.
“In those key subpopulations at high risk for recurrence [of C. difficile infection], bezlotoxumab both reduced recurrence and increased rates of global cure,” said Dr. Ciaran P. Kelly of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. The biologic was especially effective among older adults and patients with at least one recent episode of CDI, Dr. Kelly and his associates found.
Bezlotoxumab is a monoclonal antibody targeting Clostridium difficile toxin B. The international, randomized, double-blind, 12-week MODIFY I and II trials included 2,656 patients with laboratory-confirmed CDI who were randomly assigned to receive either a single intravenous dose of the biologic (10 mg per kg) or placebo in addition to standard care antibiotics – that is, oral metronidazole and vancomycin; intravenous metronidazole with oral vancomycin; oral fidaxomicin; or oral fidaxomicin with intravenous metronidazole.
In both trials, bezlotoxumab was associated with a 10% decrease in rates of recurrent CDI, compared with placebo (P = .0003). Bezlotoxumab also achieved a 9.7% increase in rates of global cure, defined as clinical cure of the initial episode with no recurrence, Dr. Kelly said.
For the current analysis, he and his associates examined the efficacy of bezlotoxumab among patients at increased risk for recurrent CDI. These patients were older than 65 years, were immunocompromised, had a history of recurrent CDI, had been diagnosed with CDI within 6 months, and/or had severe CDI or were infected with hypervirulent, binary toxin positive strain. Most patients in the trials fell into at least one of these categories, Dr. Kelly said.
For each subgroup, bezlotoxumab was associated with lower rates of CDI recurrence and higher rates of global cure than in the overall study population, he emphasized. Compared with placebo, the most dramatic improvements in recurrence and global cure rates were among older patients (a 16% decrease and a 16% increase, respectively), patients with recent CDI (a 16% increase and a 12% decrease), patients with a history of recurrent CDI (a 13% decrease and a 12% increase) and immunocompromised patients (a 13% decrease and a 15% increase).
Neither trial generated a concerning safety signal, according to Dr. Kelly. There were “slight increases” in infusion reactions in the bezlotoxumab arms, but these were mostly minor and short lived, he added. “Serious adverse events were, in fact, slightly more common in the placebo group, mainly because of adverse events related to recurrence.”
The MODIFY trials were funded by Merck. Dr. Kelly reported consulting and advisory relationships with Merck, Sanofi Pasteur, Seres Therapeutics, Summit, and Alba.
SAN DIEGO – Bezlotoxumab prevented recurrent Clostridium difficile infections (CDIs) among high-risk patients even more effectively than in the overall populations of the placebo-controlled MODIFY I and MODIFY II trials, according to a report at the annual Digestive Disease Week.
“In those key subpopulations at high risk for recurrence [of C. difficile infection], bezlotoxumab both reduced recurrence and increased rates of global cure,” said Dr. Ciaran P. Kelly of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. The biologic was especially effective among older adults and patients with at least one recent episode of CDI, Dr. Kelly and his associates found.
Bezlotoxumab is a monoclonal antibody targeting Clostridium difficile toxin B. The international, randomized, double-blind, 12-week MODIFY I and II trials included 2,656 patients with laboratory-confirmed CDI who were randomly assigned to receive either a single intravenous dose of the biologic (10 mg per kg) or placebo in addition to standard care antibiotics – that is, oral metronidazole and vancomycin; intravenous metronidazole with oral vancomycin; oral fidaxomicin; or oral fidaxomicin with intravenous metronidazole.
In both trials, bezlotoxumab was associated with a 10% decrease in rates of recurrent CDI, compared with placebo (P = .0003). Bezlotoxumab also achieved a 9.7% increase in rates of global cure, defined as clinical cure of the initial episode with no recurrence, Dr. Kelly said.
For the current analysis, he and his associates examined the efficacy of bezlotoxumab among patients at increased risk for recurrent CDI. These patients were older than 65 years, were immunocompromised, had a history of recurrent CDI, had been diagnosed with CDI within 6 months, and/or had severe CDI or were infected with hypervirulent, binary toxin positive strain. Most patients in the trials fell into at least one of these categories, Dr. Kelly said.
For each subgroup, bezlotoxumab was associated with lower rates of CDI recurrence and higher rates of global cure than in the overall study population, he emphasized. Compared with placebo, the most dramatic improvements in recurrence and global cure rates were among older patients (a 16% decrease and a 16% increase, respectively), patients with recent CDI (a 16% increase and a 12% decrease), patients with a history of recurrent CDI (a 13% decrease and a 12% increase) and immunocompromised patients (a 13% decrease and a 15% increase).
Neither trial generated a concerning safety signal, according to Dr. Kelly. There were “slight increases” in infusion reactions in the bezlotoxumab arms, but these were mostly minor and short lived, he added. “Serious adverse events were, in fact, slightly more common in the placebo group, mainly because of adverse events related to recurrence.”
The MODIFY trials were funded by Merck. Dr. Kelly reported consulting and advisory relationships with Merck, Sanofi Pasteur, Seres Therapeutics, Summit, and Alba.
AT DDW® 2016
Key clinical point: The monoclonal antibody bezlotoxumab prevented recurrent CDIs among patients at high risk for this outcome.
Major finding: Compared with placebo, bezlotoxumab achieved the most dramatic differences in rates of CDI recurrence and global cure for older patients (a 16% decrease and a 16% increase, respectively).
Data source: An analysis of the international, randomized, double-blind, 12-week MODIFY I and II trials, which included 2,656 patients with laboratory-confirmed CDI.
Disclosures: The MODIFY trials were funded by Merck. Dr. Kelly reported consulting and advisory relationships with Merck, Sanofi Pasteur, Seres Therapeutics, Summit, and Alba.
Experts present first recommendations for treating acne fulminans
SCOTTSDALE, ARIZ. – Patients with acne fulminans should first begin corticosteroid monotherapy before adding isotretinoin, according to the first evidence-based consensus recommendations on this disease.
Antibiotics should not be used as first line treatment or monotherapy for acne fulminans, according to the experts who drafted the recommendations. Acne fulminans is an uncommon, understudied, and severe disorder that “typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with fever, bone pain, and other systemic symptoms,” noted panel co-chairs Dr. Andrea Zaenglein, professor of dermatology and pediatric dermatology, Pennsylvania State University, Hershey, and Dr. Sheila Friedlander, professor of medicine and pediatrics, University of California, San Diego, together with their associates.
The recommendations – based on a full literature review, a 5-hour audioconference, and two rounds of surveys to achieve consensus on these topics – were summarized in a poster presented at the annual meeting of the Society for Investigative Dermatology.
Until now, there have been no clear guidelines on the pathogenesis, treatment, and prevention of acne fulminans, according to the panelists.
Consensus definitions
“Acne fulminans is not just an extreme form of acne, but rather, a distinct, likely auto-inflammatory disorder,” the experts stated. Affected patients typically have an “abrupt, dramatic flare of inflammatory acne, with erosions, and with or without crusts, hemorrhagic nodules/plaques, and systemic findings.”
Systemic involvement is uncommon, but when present, includes fever, malaise, bone pain, arthralgias, erythema nodosum, and leukocytosis, they noted. Some patients also have anemia, an elevated erythrocyte sedimentation rate, and an increased C-reactive protein level. Radiography typically reveals osteolytic lesions of the sternum, clavicles, sacroiliac joints, and hips.
Acne fulminans is most often triggered by isotretinoin therapy, but can occur without it, the panel said. Isotretinoin-induced acne fulminans can have systemic involvement, but usually does not.
Corticosteroids
Patients should start corticosteroid monotherapy at a dose of 0.5 to 1.0 mg per kg per day, according to the recommendations. Patients with systemic involvement should receive steroids for at least 4 weeks, and other patients should continue steroids for at least 2 weeks and until all lesions have healed.
Oral corticosteroids should be tapered slowly over about 4 to 8 weeks, first by halving the dose to a physiologic dose each week, and then by dosing every other day for 2 weeks. Topical corticosteroids also can be used for eroded sites with granulation tissue, they noted.
Isotretinoin
Ironically, isotretinoin is both a treatment and a potential trigger of acne fulminans, and the recommendations included detailed guidance on its use.
Patients should wait at least 2 weeks after crusting resolves before starting isotretinoin, and should overlap isotretinoin with corticosteroids for at least 4 weeks, the experts emphasized. They recommended starting isotretinoin at 0.1 mg per kg per day, and waiting at least 2 months to increase this dose. Because patients clear at different rates, there is no universal optimal cumulative dose of isotretinoin, they noted.
If patients on isotretinoin develop flare, crusts, and erosions, they should halt treatment and either start corticosteroids, or increase the steroid dose to 1.0 mg per kg. If crusts and erosions persist, the panelists recommended considering cyclosporine, biologics, or dapsone.
If hemorrhagic crusts or erosions resolve after stopping isotretinoin, it can be restarted at the initial dose of 0.1 mg per kg and overlapped with steroids for 4 weeks.
If flares, crusts, and erosions begin when patients on isotretinoin are tapering corticosteroids, then steroids should be continued without tapering, isotretinoin should be stopped temporarily, and it should be restarted at 0.1 mg per kg after crusts and erosions have healed. This dose should be continued for 4 weeks, and then slowly increased as tolerated.
Antibiotics
Antibiotics are not useful as monotherapy for first-line therapy for acne fulminans, according to the recommendations. But to avoid isotretinoin-induced acne fulminans, the experts often pretreat patients with oral antibiotics before starting isotretinoin, and may continue oral antibiotics during the initial phase of isotretinoin treatment. However, there have been no prospective studies supporting this approach, they noted.
Other treatment considerations
Acne fulminans lesions should not be debrided, the experts emphasized. Acne fulminans associated with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis), PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa) has responded successfully to tumor necrosis factor–alpha inhibitors and interleukin-1 receptor antagonists, they noted. Pulsed dye laser also has been used to successfully treat acne fulminans, particularly when there is associated granulation tissue, they stated.
Reducing the risk of pseudotumor cerebri syndrome
Several drugs used to treat acne fulminans have been linked to pseudotumor cerebri syndrome, the experts cautioned. “Among the tetracyclines, minocycline carries the highest risk,” they noted. Both isotretinoin and corticosteroids have been linked to pseudotumor cerebri syndrome, but clinicians can reduce this risk by avoiding an abrupt steroid taper, they emphasized.
The panel included physicians from the University of California, San Diego; Pennsylvania State University, Hershey; State University of New York, Brooklyn; Cornell University, New York; Touro University California, Vallejo; the University of California, San Francisco; the University of Pennsylvania, Philadelphia; and Jefferson Medical College, Philadelphia. They did not disclose conflicts of interest.
SCOTTSDALE, ARIZ. – Patients with acne fulminans should first begin corticosteroid monotherapy before adding isotretinoin, according to the first evidence-based consensus recommendations on this disease.
Antibiotics should not be used as first line treatment or monotherapy for acne fulminans, according to the experts who drafted the recommendations. Acne fulminans is an uncommon, understudied, and severe disorder that “typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with fever, bone pain, and other systemic symptoms,” noted panel co-chairs Dr. Andrea Zaenglein, professor of dermatology and pediatric dermatology, Pennsylvania State University, Hershey, and Dr. Sheila Friedlander, professor of medicine and pediatrics, University of California, San Diego, together with their associates.
The recommendations – based on a full literature review, a 5-hour audioconference, and two rounds of surveys to achieve consensus on these topics – were summarized in a poster presented at the annual meeting of the Society for Investigative Dermatology.
Until now, there have been no clear guidelines on the pathogenesis, treatment, and prevention of acne fulminans, according to the panelists.
Consensus definitions
“Acne fulminans is not just an extreme form of acne, but rather, a distinct, likely auto-inflammatory disorder,” the experts stated. Affected patients typically have an “abrupt, dramatic flare of inflammatory acne, with erosions, and with or without crusts, hemorrhagic nodules/plaques, and systemic findings.”
Systemic involvement is uncommon, but when present, includes fever, malaise, bone pain, arthralgias, erythema nodosum, and leukocytosis, they noted. Some patients also have anemia, an elevated erythrocyte sedimentation rate, and an increased C-reactive protein level. Radiography typically reveals osteolytic lesions of the sternum, clavicles, sacroiliac joints, and hips.
Acne fulminans is most often triggered by isotretinoin therapy, but can occur without it, the panel said. Isotretinoin-induced acne fulminans can have systemic involvement, but usually does not.
Corticosteroids
Patients should start corticosteroid monotherapy at a dose of 0.5 to 1.0 mg per kg per day, according to the recommendations. Patients with systemic involvement should receive steroids for at least 4 weeks, and other patients should continue steroids for at least 2 weeks and until all lesions have healed.
Oral corticosteroids should be tapered slowly over about 4 to 8 weeks, first by halving the dose to a physiologic dose each week, and then by dosing every other day for 2 weeks. Topical corticosteroids also can be used for eroded sites with granulation tissue, they noted.
Isotretinoin
Ironically, isotretinoin is both a treatment and a potential trigger of acne fulminans, and the recommendations included detailed guidance on its use.
Patients should wait at least 2 weeks after crusting resolves before starting isotretinoin, and should overlap isotretinoin with corticosteroids for at least 4 weeks, the experts emphasized. They recommended starting isotretinoin at 0.1 mg per kg per day, and waiting at least 2 months to increase this dose. Because patients clear at different rates, there is no universal optimal cumulative dose of isotretinoin, they noted.
If patients on isotretinoin develop flare, crusts, and erosions, they should halt treatment and either start corticosteroids, or increase the steroid dose to 1.0 mg per kg. If crusts and erosions persist, the panelists recommended considering cyclosporine, biologics, or dapsone.
If hemorrhagic crusts or erosions resolve after stopping isotretinoin, it can be restarted at the initial dose of 0.1 mg per kg and overlapped with steroids for 4 weeks.
If flares, crusts, and erosions begin when patients on isotretinoin are tapering corticosteroids, then steroids should be continued without tapering, isotretinoin should be stopped temporarily, and it should be restarted at 0.1 mg per kg after crusts and erosions have healed. This dose should be continued for 4 weeks, and then slowly increased as tolerated.
Antibiotics
Antibiotics are not useful as monotherapy for first-line therapy for acne fulminans, according to the recommendations. But to avoid isotretinoin-induced acne fulminans, the experts often pretreat patients with oral antibiotics before starting isotretinoin, and may continue oral antibiotics during the initial phase of isotretinoin treatment. However, there have been no prospective studies supporting this approach, they noted.
Other treatment considerations
Acne fulminans lesions should not be debrided, the experts emphasized. Acne fulminans associated with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis), PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa) has responded successfully to tumor necrosis factor–alpha inhibitors and interleukin-1 receptor antagonists, they noted. Pulsed dye laser also has been used to successfully treat acne fulminans, particularly when there is associated granulation tissue, they stated.
Reducing the risk of pseudotumor cerebri syndrome
Several drugs used to treat acne fulminans have been linked to pseudotumor cerebri syndrome, the experts cautioned. “Among the tetracyclines, minocycline carries the highest risk,” they noted. Both isotretinoin and corticosteroids have been linked to pseudotumor cerebri syndrome, but clinicians can reduce this risk by avoiding an abrupt steroid taper, they emphasized.
The panel included physicians from the University of California, San Diego; Pennsylvania State University, Hershey; State University of New York, Brooklyn; Cornell University, New York; Touro University California, Vallejo; the University of California, San Francisco; the University of Pennsylvania, Philadelphia; and Jefferson Medical College, Philadelphia. They did not disclose conflicts of interest.
SCOTTSDALE, ARIZ. – Patients with acne fulminans should first begin corticosteroid monotherapy before adding isotretinoin, according to the first evidence-based consensus recommendations on this disease.
Antibiotics should not be used as first line treatment or monotherapy for acne fulminans, according to the experts who drafted the recommendations. Acne fulminans is an uncommon, understudied, and severe disorder that “typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with fever, bone pain, and other systemic symptoms,” noted panel co-chairs Dr. Andrea Zaenglein, professor of dermatology and pediatric dermatology, Pennsylvania State University, Hershey, and Dr. Sheila Friedlander, professor of medicine and pediatrics, University of California, San Diego, together with their associates.
The recommendations – based on a full literature review, a 5-hour audioconference, and two rounds of surveys to achieve consensus on these topics – were summarized in a poster presented at the annual meeting of the Society for Investigative Dermatology.
Until now, there have been no clear guidelines on the pathogenesis, treatment, and prevention of acne fulminans, according to the panelists.
Consensus definitions
“Acne fulminans is not just an extreme form of acne, but rather, a distinct, likely auto-inflammatory disorder,” the experts stated. Affected patients typically have an “abrupt, dramatic flare of inflammatory acne, with erosions, and with or without crusts, hemorrhagic nodules/plaques, and systemic findings.”
Systemic involvement is uncommon, but when present, includes fever, malaise, bone pain, arthralgias, erythema nodosum, and leukocytosis, they noted. Some patients also have anemia, an elevated erythrocyte sedimentation rate, and an increased C-reactive protein level. Radiography typically reveals osteolytic lesions of the sternum, clavicles, sacroiliac joints, and hips.
Acne fulminans is most often triggered by isotretinoin therapy, but can occur without it, the panel said. Isotretinoin-induced acne fulminans can have systemic involvement, but usually does not.
Corticosteroids
Patients should start corticosteroid monotherapy at a dose of 0.5 to 1.0 mg per kg per day, according to the recommendations. Patients with systemic involvement should receive steroids for at least 4 weeks, and other patients should continue steroids for at least 2 weeks and until all lesions have healed.
Oral corticosteroids should be tapered slowly over about 4 to 8 weeks, first by halving the dose to a physiologic dose each week, and then by dosing every other day for 2 weeks. Topical corticosteroids also can be used for eroded sites with granulation tissue, they noted.
Isotretinoin
Ironically, isotretinoin is both a treatment and a potential trigger of acne fulminans, and the recommendations included detailed guidance on its use.
Patients should wait at least 2 weeks after crusting resolves before starting isotretinoin, and should overlap isotretinoin with corticosteroids for at least 4 weeks, the experts emphasized. They recommended starting isotretinoin at 0.1 mg per kg per day, and waiting at least 2 months to increase this dose. Because patients clear at different rates, there is no universal optimal cumulative dose of isotretinoin, they noted.
If patients on isotretinoin develop flare, crusts, and erosions, they should halt treatment and either start corticosteroids, or increase the steroid dose to 1.0 mg per kg. If crusts and erosions persist, the panelists recommended considering cyclosporine, biologics, or dapsone.
If hemorrhagic crusts or erosions resolve after stopping isotretinoin, it can be restarted at the initial dose of 0.1 mg per kg and overlapped with steroids for 4 weeks.
If flares, crusts, and erosions begin when patients on isotretinoin are tapering corticosteroids, then steroids should be continued without tapering, isotretinoin should be stopped temporarily, and it should be restarted at 0.1 mg per kg after crusts and erosions have healed. This dose should be continued for 4 weeks, and then slowly increased as tolerated.
Antibiotics
Antibiotics are not useful as monotherapy for first-line therapy for acne fulminans, according to the recommendations. But to avoid isotretinoin-induced acne fulminans, the experts often pretreat patients with oral antibiotics before starting isotretinoin, and may continue oral antibiotics during the initial phase of isotretinoin treatment. However, there have been no prospective studies supporting this approach, they noted.
Other treatment considerations
Acne fulminans lesions should not be debrided, the experts emphasized. Acne fulminans associated with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis), PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa) has responded successfully to tumor necrosis factor–alpha inhibitors and interleukin-1 receptor antagonists, they noted. Pulsed dye laser also has been used to successfully treat acne fulminans, particularly when there is associated granulation tissue, they stated.
Reducing the risk of pseudotumor cerebri syndrome
Several drugs used to treat acne fulminans have been linked to pseudotumor cerebri syndrome, the experts cautioned. “Among the tetracyclines, minocycline carries the highest risk,” they noted. Both isotretinoin and corticosteroids have been linked to pseudotumor cerebri syndrome, but clinicians can reduce this risk by avoiding an abrupt steroid taper, they emphasized.
The panel included physicians from the University of California, San Diego; Pennsylvania State University, Hershey; State University of New York, Brooklyn; Cornell University, New York; Touro University California, Vallejo; the University of California, San Francisco; the University of Pennsylvania, Philadelphia; and Jefferson Medical College, Philadelphia. They did not disclose conflicts of interest.
AT THE 2016 SID ANNUAL MEETING
Low-FODMAP diet eased abdominal symptoms in IBS
SAN DIEGO – For patients with diarrhea-predominant irritable bowel syndrome, avoiding FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) improved abdominal pain and bloating significantly more than following standard advice to eat smaller meals and limit caffeine and alcohol, researchers reported.
“Both diets provided adequate relief to about 40%-50% of patients, but the low-FODMAP diet led to significantly greater improvements in abdominal symptoms,” Dr. Shanti L. Eswaran of the University of Michigan, Ann Arbor, said at the annual Digestive Disease Week. Results from the randomized, controlled trial, the first of its kind in the United States, “support a role for the low-FODMAP diet in the treatment of patients with diarrhea-predominant IBS,” she added.
FODMAPs are poorly absorbed or indigestible fermentable carbohydrates that can cause bloating, flatulence, and diarrhea when eaten in excess. Hence, the low-FODMAP diet involves avoiding or limiting foods high in fructose (such as honey and dried fruit), lactose (dairy), fructans (wheat, garlic, and onions), galactans (legumes), and polyols (apples and stone fruits). Several smaller studies have linked a low-FODMAP diet to improvements in IBS, “but the existing data are limited and inconsistent, and there is no randomized, controlled trial data from adults in the United States,” Dr. Eswaran said.
To fill that gap, she and her associates randomly assigned 92 adults meeting Rome III criteria for diarrhea-predominant IBS to follow either a low-FODMAP diet or a control diet that was based on recommendations from the National Institute for Health Care and Excellence (NICE, in the United Kingdom). The modified NICE diet included eating smaller, more frequent meals, limiting caffeine and alcohol, and avoiding foods that patients knew worsened their symptoms. Both groups of patients worked with a dietitian.
At baseline, all patients reported having regular bouts of at least moderate abdominal pain and stool consistency of 5 or higher (that is, looser) on the Bristol Stool Form Scale. In all, 52% of patients on the low-FODMAP diet and 41% of patients on the control diet reported adequate symptom relief during at least one of the last 2 weeks of the study – a statistically similar level of improvement, Dr. Eswaran said. “We were really underpowered for our primary endpoint,” she added. “We had calculated a 30% difference, and we did not get anywhere near that.” In fact, enrollment in the trial ended early because many patients were already putting themselves on the low-FODMAP diet, she added.
But despite its limited power, the study uncovered significant differences in abdominal symptoms with the two diets. More than half of patients on the low-FODMAP diet reported a clinically meaningful improvement in abdominal pain, compared with only 23% of patients on the control diet (P = .008). Likewise, 52% of patients reported clinically meaningful improvement in bloating, compared with about a quarter of patients on the control diet (P = .013). Low-FODMAP patients also were more likely to report improvements in stool consistency (42%, versus 28% for control patients; P = .18). However, there was no evidence that the low-FODMAP diet improved stool consistency or urgency, Dr. Eswaran said.
“Both diets were safe and well tolerated, although dropouts were more common with the low-FODMAP diet,” the researchers noted. Dietary analyses showed that at 4 weeks, the low-FODMAP group was consuming significantly less total carbohydrates, but similar quantities of total calories, protein, fat, dietary fiber, and alcohol as the control group. “The low-FODMAP diet is not designed to be long term, because it is fairly restrictive,” Dr. Eswaran commented. “I think it would be a good idea for the next set of studies to see how long patients can stay on it, and what factors are necessary for them to do so.”
Dr. Eswaran had no disclosures.
SAN DIEGO – For patients with diarrhea-predominant irritable bowel syndrome, avoiding FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) improved abdominal pain and bloating significantly more than following standard advice to eat smaller meals and limit caffeine and alcohol, researchers reported.
“Both diets provided adequate relief to about 40%-50% of patients, but the low-FODMAP diet led to significantly greater improvements in abdominal symptoms,” Dr. Shanti L. Eswaran of the University of Michigan, Ann Arbor, said at the annual Digestive Disease Week. Results from the randomized, controlled trial, the first of its kind in the United States, “support a role for the low-FODMAP diet in the treatment of patients with diarrhea-predominant IBS,” she added.
FODMAPs are poorly absorbed or indigestible fermentable carbohydrates that can cause bloating, flatulence, and diarrhea when eaten in excess. Hence, the low-FODMAP diet involves avoiding or limiting foods high in fructose (such as honey and dried fruit), lactose (dairy), fructans (wheat, garlic, and onions), galactans (legumes), and polyols (apples and stone fruits). Several smaller studies have linked a low-FODMAP diet to improvements in IBS, “but the existing data are limited and inconsistent, and there is no randomized, controlled trial data from adults in the United States,” Dr. Eswaran said.
To fill that gap, she and her associates randomly assigned 92 adults meeting Rome III criteria for diarrhea-predominant IBS to follow either a low-FODMAP diet or a control diet that was based on recommendations from the National Institute for Health Care and Excellence (NICE, in the United Kingdom). The modified NICE diet included eating smaller, more frequent meals, limiting caffeine and alcohol, and avoiding foods that patients knew worsened their symptoms. Both groups of patients worked with a dietitian.
At baseline, all patients reported having regular bouts of at least moderate abdominal pain and stool consistency of 5 or higher (that is, looser) on the Bristol Stool Form Scale. In all, 52% of patients on the low-FODMAP diet and 41% of patients on the control diet reported adequate symptom relief during at least one of the last 2 weeks of the study – a statistically similar level of improvement, Dr. Eswaran said. “We were really underpowered for our primary endpoint,” she added. “We had calculated a 30% difference, and we did not get anywhere near that.” In fact, enrollment in the trial ended early because many patients were already putting themselves on the low-FODMAP diet, she added.
But despite its limited power, the study uncovered significant differences in abdominal symptoms with the two diets. More than half of patients on the low-FODMAP diet reported a clinically meaningful improvement in abdominal pain, compared with only 23% of patients on the control diet (P = .008). Likewise, 52% of patients reported clinically meaningful improvement in bloating, compared with about a quarter of patients on the control diet (P = .013). Low-FODMAP patients also were more likely to report improvements in stool consistency (42%, versus 28% for control patients; P = .18). However, there was no evidence that the low-FODMAP diet improved stool consistency or urgency, Dr. Eswaran said.
“Both diets were safe and well tolerated, although dropouts were more common with the low-FODMAP diet,” the researchers noted. Dietary analyses showed that at 4 weeks, the low-FODMAP group was consuming significantly less total carbohydrates, but similar quantities of total calories, protein, fat, dietary fiber, and alcohol as the control group. “The low-FODMAP diet is not designed to be long term, because it is fairly restrictive,” Dr. Eswaran commented. “I think it would be a good idea for the next set of studies to see how long patients can stay on it, and what factors are necessary for them to do so.”
Dr. Eswaran had no disclosures.
SAN DIEGO – For patients with diarrhea-predominant irritable bowel syndrome, avoiding FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) improved abdominal pain and bloating significantly more than following standard advice to eat smaller meals and limit caffeine and alcohol, researchers reported.
“Both diets provided adequate relief to about 40%-50% of patients, but the low-FODMAP diet led to significantly greater improvements in abdominal symptoms,” Dr. Shanti L. Eswaran of the University of Michigan, Ann Arbor, said at the annual Digestive Disease Week. Results from the randomized, controlled trial, the first of its kind in the United States, “support a role for the low-FODMAP diet in the treatment of patients with diarrhea-predominant IBS,” she added.
FODMAPs are poorly absorbed or indigestible fermentable carbohydrates that can cause bloating, flatulence, and diarrhea when eaten in excess. Hence, the low-FODMAP diet involves avoiding or limiting foods high in fructose (such as honey and dried fruit), lactose (dairy), fructans (wheat, garlic, and onions), galactans (legumes), and polyols (apples and stone fruits). Several smaller studies have linked a low-FODMAP diet to improvements in IBS, “but the existing data are limited and inconsistent, and there is no randomized, controlled trial data from adults in the United States,” Dr. Eswaran said.
To fill that gap, she and her associates randomly assigned 92 adults meeting Rome III criteria for diarrhea-predominant IBS to follow either a low-FODMAP diet or a control diet that was based on recommendations from the National Institute for Health Care and Excellence (NICE, in the United Kingdom). The modified NICE diet included eating smaller, more frequent meals, limiting caffeine and alcohol, and avoiding foods that patients knew worsened their symptoms. Both groups of patients worked with a dietitian.
At baseline, all patients reported having regular bouts of at least moderate abdominal pain and stool consistency of 5 or higher (that is, looser) on the Bristol Stool Form Scale. In all, 52% of patients on the low-FODMAP diet and 41% of patients on the control diet reported adequate symptom relief during at least one of the last 2 weeks of the study – a statistically similar level of improvement, Dr. Eswaran said. “We were really underpowered for our primary endpoint,” she added. “We had calculated a 30% difference, and we did not get anywhere near that.” In fact, enrollment in the trial ended early because many patients were already putting themselves on the low-FODMAP diet, she added.
But despite its limited power, the study uncovered significant differences in abdominal symptoms with the two diets. More than half of patients on the low-FODMAP diet reported a clinically meaningful improvement in abdominal pain, compared with only 23% of patients on the control diet (P = .008). Likewise, 52% of patients reported clinically meaningful improvement in bloating, compared with about a quarter of patients on the control diet (P = .013). Low-FODMAP patients also were more likely to report improvements in stool consistency (42%, versus 28% for control patients; P = .18). However, there was no evidence that the low-FODMAP diet improved stool consistency or urgency, Dr. Eswaran said.
“Both diets were safe and well tolerated, although dropouts were more common with the low-FODMAP diet,” the researchers noted. Dietary analyses showed that at 4 weeks, the low-FODMAP group was consuming significantly less total carbohydrates, but similar quantities of total calories, protein, fat, dietary fiber, and alcohol as the control group. “The low-FODMAP diet is not designed to be long term, because it is fairly restrictive,” Dr. Eswaran commented. “I think it would be a good idea for the next set of studies to see how long patients can stay on it, and what factors are necessary for them to do so.”
Dr. Eswaran had no disclosures.
AT DDW® 2016
Key clinical point: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols was associated with significant and clinically meaningful improvements in the abdominal symptoms of diarrhea-predominant irritable bowel syndrome.
Major finding: About half of patients on the low-FODMAP diet improved, compared with about a quarter of patients on a common-sense control diet.
Data source: A prospective, single-center, single-blind randomized controlled trial of 92 adults with IBS with diarrhea (Rome III).
Disclosures: Dr. Eswaren had no disclosures.
HCV regimen found safe, effective in patients with severe renal disease
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
FROM GASTROENTEROLOGY
Key clinical point: Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir cured 90% of patients with hepatitis C virus infection and severe or end-stage renal disease.
Major finding: The rate of SVR12 was 90% (95% CI, 70%-97%).
Data source: A single-arm, open-label, multicenter trial of 20 noncirrhotic genotype 1 HCV-infected adults with stage 4 or 5 chronic kidney disease.
Disclosures: AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
VIDEO: Asymptomatic pancreatic cysts rarely became malignant
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Asymptomatic neoplastic pancreatic cysts rarely become malignant, especially in the absence of multiple American Gastroenterological Association high-risk features.
Major finding: Only 1% of patients developed invasive pancreatic adenocarcinoma after more than 5 years of surveillance.
Data source: A multicenter retrospective study of 310 patients who underwent endoscopic ultrasound evaluations of pancreatic cysts.
Disclosures: The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
VIDEO: High sensitivity–CRP, IL-6 predicted inflammatory bowel disease
Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.
The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”
SOURCE: American Gastroenterological Society
The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).
Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.
Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”
The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.
Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.
The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”
SOURCE: American Gastroenterological Society
The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).
Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.
Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”
The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.
Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.
The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”
SOURCE: American Gastroenterological Society
The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).
Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.
Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”
The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Patients might have subclinical inflammation for several years before developing inflammatory bowel disease.
Major finding: Participants testing in the highest quintiles for circulating high-sensitivity C-reactive protein and interleukin-6 were at greater risk of Crohn’s disease and ulcerative colitis, compared with individuals testing in the lowest quintiles for each marker, with estimated odds ratios of 1.8, 2.8, 3.4, and 4.7.
Data source: A prospective nested case-control study of female nurses, including 83 with Crohn’s disease, 90 with ulcerative colitis, and 344 matched controls.
Disclosures: The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.
Combination OCs tied to increased risk of surgery for Crohn’s
Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.
“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.
Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).
During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.
Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.
The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.
Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.
“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.
Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).
During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.
Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.
The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.
Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.
“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.
Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).
During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.
Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.
The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.
FROM GASTROENTEROLOGY
Key clinical point: Long-term use of combination oral contraceptives significantly increased the risk of surgery among women with Crohn’s disease.
Major finding: Women who used combination OCs for more than 3 years were 68% more likely to need surgery than were nonusers.
Data source: A prospective national registry study of 4,036 women with Crohn’s disease.
Disclosures: The study was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.
