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DDW: Uveitis significantly more common in black patients with IBD
WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.
Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.
The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.
Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.
In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).
More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).
After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.
The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.
Dr. Badamas had no relevant disclosures.
WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.
Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.
The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.
Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.
In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).
More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).
After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.
The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.
Dr. Badamas had no relevant disclosures.
WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.
Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.
The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.
Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.
In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).
More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).
After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.
The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.
Dr. Badamas had no relevant disclosures.
AT DDW 2015
Key clinical point: The finding that uveitis was more common among black patients with inflammatory bowel disease (IBD) may justify screening this group of patients for uveitis.
Major finding: Black patients with IBD were 1.5 times more likely to have at least one extraintestinal manifestation of IBD and about twice as likely to have uveitis than were white patients – statistically significant differences in a study of more than 500 patients with IBD.
Data source: Study of extraintestinal manifestations of IBD in 196 black patients and 342 white patients with Crohn’s disease or ulcerative colitis, treated at Johns Hopkins clinics, who are part of the Multicenter African-American Inflammatory Bowel Disease Study (MAAIS).
Disclosures: Dr. Badamas had no relevant disclosures.
DDW: Gestational diabetes linked to increased NAFLD risk in middle age
WASHINGTON – Gestational diabetes was identified as a significant, independent risk factor for developing non-alcoholic fatty liver disease later in life, according to a study of more than 1,000 women followed for 25 years.
This study “is the first to show a strong association between gestational diabetes in young adulthood and non-alcoholic fatty liver disease in middle-age,” Dr. Veeral Ajmera of the department of gastroenterology at the University of California, San Francisco, reported at the annual Digestive Disease Week.
The study evaluated 1,115 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, who had at least one delivery, did not have a diabetes diagnosis before pregnancy, and had a CT evaluation for hepatic steatosis at the 25-year visit, in 2010 and 2011. Women were excluded if they did not have a complete CT scan at that time, they had more than 14 drinks of alcohol per week, used medications associated with steatosis, or had chronic viral hepatitis or HIV infections.
At baseline the median age was 25-26 years, about 55%-56% were black, and the prevalence of hypertension (2%-3%) and dyslipidemia were similar. The CARDIA study enrolled about 5,100 men and women aged 18-30 years at four U.S. medical centers in the mid 1980s. Patients had 7 study visits over a 25-year follow-up period.
Of the 1,115 women evaluated, 124 (11%) went on to develop GDM and 75 (7%) met the CT definition for NAFLD (liver attenuation less than or equal to 40 Hounsfield units on CT scan) by the 25-year follow-up, when they were a median age of 50-51 years.
At 25 years, 14% of those with a history of GDM had NAFLD, compared with 5.8% of those who did not have GDM, for an unadjusted odds ratio of 2.56 (p <0.01), Dr. Ajmera said.
In the statistical analysis, the researchers determined that baseline homeostatic model assessment of insulin resistance (HOMA-IR) and baseline triglycerides were also ”strongly associated” with NAFLD at year 25.
“Importantly,” he noted, the measure of the association between GDM and NAFLD remained statistically significant, after adjusting for these covariates (OR, 2.29). At the start of the study, women who went on to develop GDM had significantly higher body mass index (BMI), HOMA-IR, waist circumference, and triglycerides than those who did not develop GDM, but the magnitude of those differences was small.
Additionally, after adjustment for a diagnosis of diabetes at year 25, the association between a history of GDM and NAFLD was stronger (OR, 1.99) than the association between a diagnosis of diabetes at year 25 and NAFLD (OR, 1.5), he said.
The researchers added BMI to their multivariate analysis to determine whether women with a gestational diabetes history gained more weight, and whether that weight explained the increased prevalence of NAFLD, “and found that the association between gestational diabetes and non-alcoholic fatty liver disease remained,” Dr. Ajmera added.
Evaluations of race, baseline BMI, and baseline HOMA-IR as effect modifiers of the relationship between GDM and NAFLD were not significant.
“Gestational diabetes represents insulin resistance unmasked by the stress of pregnancy, and offers the unique opportunity to identify those at risk of NAFLD at a young age,” Dr. Ajmera concluded.
Limitations of the study included not being able to determine if the women had NAFLD before they were diagnosed with GDM. However, based on the participants’ young age at enrollment, that is unlikely, he said. In addition, the researchers had no information on liver biochemistry tests, which, however, are not sensitive or specific for diagnosing NAFLD. The strengths of the study include the length of follow-up of a large biracial population, with measurement of well-characterized metabolic covariates measured, he added.
Dr. Ajmera reported having no relevant financial disclosures. The CARDIA study is supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
Nonalcoholic fatty liver disease is the most common and fastest growing liver disease worldwide. Identifying individuals at high risk for NAFLD remains challenging. Dr. Ajmera and his colleagues highlight the association between gestational diabetes mellitus (GDM) and NAFLD. Their work confirms and extends earlier studies that reported increased hepatic fat content and a substantially increased risk for NAFLD, in women with a prior history of GDM. In the present study, a more racially diverse U.S.-based population was followed for a much longer duration than was previous cohorts. After adjusted multivariate analysis, GDM remained a strong, independent predictor of future NAFLD. Indeed, GDM was a a better NAFLD predictor than the diagnosis of diabetes alone was. It is unclear if prepregnancy NAFLD might have affected the risk for GDM, as subjects were not assessed for hepatic steatosis or liver test elevations at baseline. Also, the percentage of 50-year-old women with NAFLD was much lower in this cohort (7%) than in the general U.S. population (at least 25%), perhaps because the study population was enriched with individuals who are typically at low risk for NAFLD (i.e., African Americans, people with low body mass index, and/or low serum triglycerides).
Additional research is needed to clarify these issues and to investigate how maternal GDM affected the health of their children. Intrauterine exposure to metabolic stresses increases the risk for obesity and other metabolic disorders later in life, suggesting that offspring of mothers with GDM may require specialized surveillance or other precautions during childhood. Given that more young women are entering their reproductive years affected by diabetes and obesity, increased attention to these issues will be required to curb the growing public health burden of NAFLD.
Dr. Cynthia A. Moylan, M.H.S., is assistant professor of medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, N.C. She is has no relevant financial conflicts of interests.
Nonalcoholic fatty liver disease is the most common and fastest growing liver disease worldwide. Identifying individuals at high risk for NAFLD remains challenging. Dr. Ajmera and his colleagues highlight the association between gestational diabetes mellitus (GDM) and NAFLD. Their work confirms and extends earlier studies that reported increased hepatic fat content and a substantially increased risk for NAFLD, in women with a prior history of GDM. In the present study, a more racially diverse U.S.-based population was followed for a much longer duration than was previous cohorts. After adjusted multivariate analysis, GDM remained a strong, independent predictor of future NAFLD. Indeed, GDM was a a better NAFLD predictor than the diagnosis of diabetes alone was. It is unclear if prepregnancy NAFLD might have affected the risk for GDM, as subjects were not assessed for hepatic steatosis or liver test elevations at baseline. Also, the percentage of 50-year-old women with NAFLD was much lower in this cohort (7%) than in the general U.S. population (at least 25%), perhaps because the study population was enriched with individuals who are typically at low risk for NAFLD (i.e., African Americans, people with low body mass index, and/or low serum triglycerides).
Additional research is needed to clarify these issues and to investigate how maternal GDM affected the health of their children. Intrauterine exposure to metabolic stresses increases the risk for obesity and other metabolic disorders later in life, suggesting that offspring of mothers with GDM may require specialized surveillance or other precautions during childhood. Given that more young women are entering their reproductive years affected by diabetes and obesity, increased attention to these issues will be required to curb the growing public health burden of NAFLD.
Dr. Cynthia A. Moylan, M.H.S., is assistant professor of medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, N.C. She is has no relevant financial conflicts of interests.
Nonalcoholic fatty liver disease is the most common and fastest growing liver disease worldwide. Identifying individuals at high risk for NAFLD remains challenging. Dr. Ajmera and his colleagues highlight the association between gestational diabetes mellitus (GDM) and NAFLD. Their work confirms and extends earlier studies that reported increased hepatic fat content and a substantially increased risk for NAFLD, in women with a prior history of GDM. In the present study, a more racially diverse U.S.-based population was followed for a much longer duration than was previous cohorts. After adjusted multivariate analysis, GDM remained a strong, independent predictor of future NAFLD. Indeed, GDM was a a better NAFLD predictor than the diagnosis of diabetes alone was. It is unclear if prepregnancy NAFLD might have affected the risk for GDM, as subjects were not assessed for hepatic steatosis or liver test elevations at baseline. Also, the percentage of 50-year-old women with NAFLD was much lower in this cohort (7%) than in the general U.S. population (at least 25%), perhaps because the study population was enriched with individuals who are typically at low risk for NAFLD (i.e., African Americans, people with low body mass index, and/or low serum triglycerides).
Additional research is needed to clarify these issues and to investigate how maternal GDM affected the health of their children. Intrauterine exposure to metabolic stresses increases the risk for obesity and other metabolic disorders later in life, suggesting that offspring of mothers with GDM may require specialized surveillance or other precautions during childhood. Given that more young women are entering their reproductive years affected by diabetes and obesity, increased attention to these issues will be required to curb the growing public health burden of NAFLD.
Dr. Cynthia A. Moylan, M.H.S., is assistant professor of medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, N.C. She is has no relevant financial conflicts of interests.
WASHINGTON – Gestational diabetes was identified as a significant, independent risk factor for developing non-alcoholic fatty liver disease later in life, according to a study of more than 1,000 women followed for 25 years.
This study “is the first to show a strong association between gestational diabetes in young adulthood and non-alcoholic fatty liver disease in middle-age,” Dr. Veeral Ajmera of the department of gastroenterology at the University of California, San Francisco, reported at the annual Digestive Disease Week.
The study evaluated 1,115 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, who had at least one delivery, did not have a diabetes diagnosis before pregnancy, and had a CT evaluation for hepatic steatosis at the 25-year visit, in 2010 and 2011. Women were excluded if they did not have a complete CT scan at that time, they had more than 14 drinks of alcohol per week, used medications associated with steatosis, or had chronic viral hepatitis or HIV infections.
At baseline the median age was 25-26 years, about 55%-56% were black, and the prevalence of hypertension (2%-3%) and dyslipidemia were similar. The CARDIA study enrolled about 5,100 men and women aged 18-30 years at four U.S. medical centers in the mid 1980s. Patients had 7 study visits over a 25-year follow-up period.
Of the 1,115 women evaluated, 124 (11%) went on to develop GDM and 75 (7%) met the CT definition for NAFLD (liver attenuation less than or equal to 40 Hounsfield units on CT scan) by the 25-year follow-up, when they were a median age of 50-51 years.
At 25 years, 14% of those with a history of GDM had NAFLD, compared with 5.8% of those who did not have GDM, for an unadjusted odds ratio of 2.56 (p <0.01), Dr. Ajmera said.
In the statistical analysis, the researchers determined that baseline homeostatic model assessment of insulin resistance (HOMA-IR) and baseline triglycerides were also ”strongly associated” with NAFLD at year 25.
“Importantly,” he noted, the measure of the association between GDM and NAFLD remained statistically significant, after adjusting for these covariates (OR, 2.29). At the start of the study, women who went on to develop GDM had significantly higher body mass index (BMI), HOMA-IR, waist circumference, and triglycerides than those who did not develop GDM, but the magnitude of those differences was small.
Additionally, after adjustment for a diagnosis of diabetes at year 25, the association between a history of GDM and NAFLD was stronger (OR, 1.99) than the association between a diagnosis of diabetes at year 25 and NAFLD (OR, 1.5), he said.
The researchers added BMI to their multivariate analysis to determine whether women with a gestational diabetes history gained more weight, and whether that weight explained the increased prevalence of NAFLD, “and found that the association between gestational diabetes and non-alcoholic fatty liver disease remained,” Dr. Ajmera added.
Evaluations of race, baseline BMI, and baseline HOMA-IR as effect modifiers of the relationship between GDM and NAFLD were not significant.
“Gestational diabetes represents insulin resistance unmasked by the stress of pregnancy, and offers the unique opportunity to identify those at risk of NAFLD at a young age,” Dr. Ajmera concluded.
Limitations of the study included not being able to determine if the women had NAFLD before they were diagnosed with GDM. However, based on the participants’ young age at enrollment, that is unlikely, he said. In addition, the researchers had no information on liver biochemistry tests, which, however, are not sensitive or specific for diagnosing NAFLD. The strengths of the study include the length of follow-up of a large biracial population, with measurement of well-characterized metabolic covariates measured, he added.
Dr. Ajmera reported having no relevant financial disclosures. The CARDIA study is supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
WASHINGTON – Gestational diabetes was identified as a significant, independent risk factor for developing non-alcoholic fatty liver disease later in life, according to a study of more than 1,000 women followed for 25 years.
This study “is the first to show a strong association between gestational diabetes in young adulthood and non-alcoholic fatty liver disease in middle-age,” Dr. Veeral Ajmera of the department of gastroenterology at the University of California, San Francisco, reported at the annual Digestive Disease Week.
The study evaluated 1,115 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, who had at least one delivery, did not have a diabetes diagnosis before pregnancy, and had a CT evaluation for hepatic steatosis at the 25-year visit, in 2010 and 2011. Women were excluded if they did not have a complete CT scan at that time, they had more than 14 drinks of alcohol per week, used medications associated with steatosis, or had chronic viral hepatitis or HIV infections.
At baseline the median age was 25-26 years, about 55%-56% were black, and the prevalence of hypertension (2%-3%) and dyslipidemia were similar. The CARDIA study enrolled about 5,100 men and women aged 18-30 years at four U.S. medical centers in the mid 1980s. Patients had 7 study visits over a 25-year follow-up period.
Of the 1,115 women evaluated, 124 (11%) went on to develop GDM and 75 (7%) met the CT definition for NAFLD (liver attenuation less than or equal to 40 Hounsfield units on CT scan) by the 25-year follow-up, when they were a median age of 50-51 years.
At 25 years, 14% of those with a history of GDM had NAFLD, compared with 5.8% of those who did not have GDM, for an unadjusted odds ratio of 2.56 (p <0.01), Dr. Ajmera said.
In the statistical analysis, the researchers determined that baseline homeostatic model assessment of insulin resistance (HOMA-IR) and baseline triglycerides were also ”strongly associated” with NAFLD at year 25.
“Importantly,” he noted, the measure of the association between GDM and NAFLD remained statistically significant, after adjusting for these covariates (OR, 2.29). At the start of the study, women who went on to develop GDM had significantly higher body mass index (BMI), HOMA-IR, waist circumference, and triglycerides than those who did not develop GDM, but the magnitude of those differences was small.
Additionally, after adjustment for a diagnosis of diabetes at year 25, the association between a history of GDM and NAFLD was stronger (OR, 1.99) than the association between a diagnosis of diabetes at year 25 and NAFLD (OR, 1.5), he said.
The researchers added BMI to their multivariate analysis to determine whether women with a gestational diabetes history gained more weight, and whether that weight explained the increased prevalence of NAFLD, “and found that the association between gestational diabetes and non-alcoholic fatty liver disease remained,” Dr. Ajmera added.
Evaluations of race, baseline BMI, and baseline HOMA-IR as effect modifiers of the relationship between GDM and NAFLD were not significant.
“Gestational diabetes represents insulin resistance unmasked by the stress of pregnancy, and offers the unique opportunity to identify those at risk of NAFLD at a young age,” Dr. Ajmera concluded.
Limitations of the study included not being able to determine if the women had NAFLD before they were diagnosed with GDM. However, based on the participants’ young age at enrollment, that is unlikely, he said. In addition, the researchers had no information on liver biochemistry tests, which, however, are not sensitive or specific for diagnosing NAFLD. The strengths of the study include the length of follow-up of a large biracial population, with measurement of well-characterized metabolic covariates measured, he added.
Dr. Ajmera reported having no relevant financial disclosures. The CARDIA study is supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
AT DDW® 2015
Key clinical point: Gestational diabetes could be used to identify young women at increased risk of having non-alcoholic fatty liver disease (NAFLD) in middle age.
Major finding: Having been diagnosed with gestational diabetes was associated with about a two-fold increased risk of having NAFLD in middle age.
Data source: The research involved 1,115 women enrolled in the 25-year Coronary Artery Risk Development in Young Adults (CARDIA) study.
Disclosures: Dr. Ajmera reported having no relevant financial disclosures. The CARDIA study is supported by the National Heart, Lung, and Blood Institute.
DDW: HBV, tuberculosis reactivations rare in IBD patients on biologic therapy
WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.
The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.
Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”
Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.
They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.
They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.
They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.
The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.
Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.
The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.
Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.
His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.
WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.
The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.
Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”
Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.
They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.
They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.
They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.
The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.
Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.
The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.
Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.
His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.
WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.
The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.
Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”
Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.
They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.
They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.
They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.
The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.
Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.
The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.
Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.
His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.
AT DDW 2015
Key clinical point: Significant clinical events related to tuberculosis and hepatitis B virus reactivation after initiating anti–tumor necrosis factor therapy in a screened population are rare.
Major finding: Rates of tuberculosis and HBV were estimated at 2.8 and less than 1.4 cases per 10,000 patient-years of exposure to treatment, respectively, in a large, fairly well screened national cohort of veterans with IBD treated with an anti-TNF drug.
Data source: A retrospective cohort study evaluated the rates of tuberculosis and HBV reactivation, identifying cases of IBD treated with anti-TNF therapy in a Veterans Health Administration database during 2003-2011, confirming cases, treatment, and HBV and TB screening status with electronic medical record review.
Disclosures: Dr. Hou’s financial disclosure includes receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and Abbvie.
AAN: Finding ways to improve door-to-needle times in stroke treatment
WASHINGTON – A streamlined emergency care service and a low-cost, tablet-based mobile telestroke system are two examples of shortening the time it takes for acute ischemic stroke patients to receive thrombolytic therapy that were presented at the annual meeting of the American Academy of Neurology.
American Heart Association/American Stroke Association guidelines recommend a door-to-needle (DTN) time of 60 minutes or less and set a goal for participating hospitals to administer tissue plasminogen activator (TPA) to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.
Dr. Judd Jensen described the efforts of Swedish Medical Center, Englewood, Colo. to streamline the emergency care of patients suspected of having an acute ischemic stroke after a task force determined that their previous “sequential, step-by-step process” wasted time. The median DTN time at the hospital’s stroke center had dropped from 46 minutes in 2010 to 39 minutes in 2013, which was better than the national average, “but we felt we could do better,” said Dr. Jensen, a neurologist at the hospital.
The process was modified so that more of the activities take place simultaneously, which includes immediately sending patients for a CT scan before entering the emergency department and administering IV TPA in the CT area to eligible patients, he explained. Previously, these patients were taken to a bed in the ED on arrival, registered, then examined by the emergency physician and neurologist and transported for a CT scan and then transported back to the ED where TPA was administered, if indicated, after several other steps were completed, including interpreting the CT scan, deciding about treatment, acquiring consent, and contacting the pharmacy to mix the TPA.
This process was improved by increasing pre-hospital notification by emergency medical services (EMS) and establishing a “launchpad” area in the back of the ED where the stroke team meets after EMS notification. On arrival, patients are transferred directly to the CT room where they are examined. The pharmacy is instructed to mix the TPA if an ischemic stroke is suspected, and the TPA is brought to the CT room where a stroke neurologist evaluates the CT scan and TPA is administered if indicated.
The impact of the revised process was evaluated in a prospective study of 262 acute ischemic stroke patients who received IV TPA between January 2010 and December 2014 at the hospital. They had a mean age of 73 years, 44% were male, and 84% were white. Their mean initial National Institutes of Health Stroke Scale (NIHSS) score was 12. The median DTN times dropped to a median of 31 minutes in 2014, Dr. Jensen said.
In 2014, almost 50% of the patients received TPA in 30 minutes or less, compared with about 25% in 2011, 2012, and 2013, he added, noting that 11 minutes was the fastest DTN time in 2014. Patients with an excellent discharge modified Rankin Scale (mRS) score (0 or 1) improved from 31% in 2010 and 30% in 2013 to 46% in 2014. During the time period studied, two patients had a symptomatic intracerebral hemorrhage, one in 2010 and another in 2012.
Dr. Jensen described the process as a multidisciplinary team effort, noting that it is important that emergency room physicians feel comfortable with the administration of TPA in the CT scan area, “because it is still their patient being administered a potentially fatal drug outside of the ED.”
At the meeting, Matthew Padrick, a medical student at the University of Virginia, Charlottesville, presented the results of a pilot study that targeted the EMS transport time as an “untapped treatment window” to improve the time to thrombolytic treatment using a low-cost mobile telestroke system to evaluate patients in the ambulance on their way to the hospital.
Because the catchment area covered by UVA includes a large rural area, transport times to the stroke center can be as long as 30 to 60 minutes, Mr. Padrick said.
In the “Improving Treatment with Rapid Evaluation of Acute Stroke via mobile Telemedicine” (iTREAT) study, he and his associates evaluated the feasibility and reliability of performing acute stroke assessments (with the NIHSS) in the ambulance. The iTREAT system, which includes an Apple iPad with retina display attached to the patient stretcher with an extendable clamp, a secure video conferencing application, a high-speed 4G LTE modem, a magnetic antenna on top of the ambulance, and the regional cellular network, “providing seamless connectivity,” he said. At a total cost of under $2,000, the system is designed so that the neurologist can evaluate the patient remotely, via the iPad.
Acting as patients, three medical students were given two unique stroke scenarios each, with stories and specific instructions; vascular neurologists did a face-to-face assessment and a remote iTREAT assessment from the hospital as the students traveled along the major routes to UVA Medical Center. NIHSS scores in the ambulance with the iTREAT system and with face-to-face assessments correlated well, with an overall intraclass correlation of 0.98, Mr. Padrick reported.
The ratings of audio-video quality during the iTREAT evaluations were judged to be ”good” or “excellent” and the NIHSS correlations and audio-video quality ratings improved with time, he added.
“We currently have IRB approval to move forward with real, live patient encounters and we are currently outfitting and training our local EMS agencies” with the system, Mr. Padrick said in an interview after the meeting.
Mr. Padrick has received research support from the American Heart Association. Dr. Judd had nothing to disclose.
WASHINGTON – A streamlined emergency care service and a low-cost, tablet-based mobile telestroke system are two examples of shortening the time it takes for acute ischemic stroke patients to receive thrombolytic therapy that were presented at the annual meeting of the American Academy of Neurology.
American Heart Association/American Stroke Association guidelines recommend a door-to-needle (DTN) time of 60 minutes or less and set a goal for participating hospitals to administer tissue plasminogen activator (TPA) to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.
Dr. Judd Jensen described the efforts of Swedish Medical Center, Englewood, Colo. to streamline the emergency care of patients suspected of having an acute ischemic stroke after a task force determined that their previous “sequential, step-by-step process” wasted time. The median DTN time at the hospital’s stroke center had dropped from 46 minutes in 2010 to 39 minutes in 2013, which was better than the national average, “but we felt we could do better,” said Dr. Jensen, a neurologist at the hospital.
The process was modified so that more of the activities take place simultaneously, which includes immediately sending patients for a CT scan before entering the emergency department and administering IV TPA in the CT area to eligible patients, he explained. Previously, these patients were taken to a bed in the ED on arrival, registered, then examined by the emergency physician and neurologist and transported for a CT scan and then transported back to the ED where TPA was administered, if indicated, after several other steps were completed, including interpreting the CT scan, deciding about treatment, acquiring consent, and contacting the pharmacy to mix the TPA.
This process was improved by increasing pre-hospital notification by emergency medical services (EMS) and establishing a “launchpad” area in the back of the ED where the stroke team meets after EMS notification. On arrival, patients are transferred directly to the CT room where they are examined. The pharmacy is instructed to mix the TPA if an ischemic stroke is suspected, and the TPA is brought to the CT room where a stroke neurologist evaluates the CT scan and TPA is administered if indicated.
The impact of the revised process was evaluated in a prospective study of 262 acute ischemic stroke patients who received IV TPA between January 2010 and December 2014 at the hospital. They had a mean age of 73 years, 44% were male, and 84% were white. Their mean initial National Institutes of Health Stroke Scale (NIHSS) score was 12. The median DTN times dropped to a median of 31 minutes in 2014, Dr. Jensen said.
In 2014, almost 50% of the patients received TPA in 30 minutes or less, compared with about 25% in 2011, 2012, and 2013, he added, noting that 11 minutes was the fastest DTN time in 2014. Patients with an excellent discharge modified Rankin Scale (mRS) score (0 or 1) improved from 31% in 2010 and 30% in 2013 to 46% in 2014. During the time period studied, two patients had a symptomatic intracerebral hemorrhage, one in 2010 and another in 2012.
Dr. Jensen described the process as a multidisciplinary team effort, noting that it is important that emergency room physicians feel comfortable with the administration of TPA in the CT scan area, “because it is still their patient being administered a potentially fatal drug outside of the ED.”
At the meeting, Matthew Padrick, a medical student at the University of Virginia, Charlottesville, presented the results of a pilot study that targeted the EMS transport time as an “untapped treatment window” to improve the time to thrombolytic treatment using a low-cost mobile telestroke system to evaluate patients in the ambulance on their way to the hospital.
Because the catchment area covered by UVA includes a large rural area, transport times to the stroke center can be as long as 30 to 60 minutes, Mr. Padrick said.
In the “Improving Treatment with Rapid Evaluation of Acute Stroke via mobile Telemedicine” (iTREAT) study, he and his associates evaluated the feasibility and reliability of performing acute stroke assessments (with the NIHSS) in the ambulance. The iTREAT system, which includes an Apple iPad with retina display attached to the patient stretcher with an extendable clamp, a secure video conferencing application, a high-speed 4G LTE modem, a magnetic antenna on top of the ambulance, and the regional cellular network, “providing seamless connectivity,” he said. At a total cost of under $2,000, the system is designed so that the neurologist can evaluate the patient remotely, via the iPad.
Acting as patients, three medical students were given two unique stroke scenarios each, with stories and specific instructions; vascular neurologists did a face-to-face assessment and a remote iTREAT assessment from the hospital as the students traveled along the major routes to UVA Medical Center. NIHSS scores in the ambulance with the iTREAT system and with face-to-face assessments correlated well, with an overall intraclass correlation of 0.98, Mr. Padrick reported.
The ratings of audio-video quality during the iTREAT evaluations were judged to be ”good” or “excellent” and the NIHSS correlations and audio-video quality ratings improved with time, he added.
“We currently have IRB approval to move forward with real, live patient encounters and we are currently outfitting and training our local EMS agencies” with the system, Mr. Padrick said in an interview after the meeting.
Mr. Padrick has received research support from the American Heart Association. Dr. Judd had nothing to disclose.
WASHINGTON – A streamlined emergency care service and a low-cost, tablet-based mobile telestroke system are two examples of shortening the time it takes for acute ischemic stroke patients to receive thrombolytic therapy that were presented at the annual meeting of the American Academy of Neurology.
American Heart Association/American Stroke Association guidelines recommend a door-to-needle (DTN) time of 60 minutes or less and set a goal for participating hospitals to administer tissue plasminogen activator (TPA) to at least 50% of their patients with acute ischemic stroke within 60 minutes of arriving at the hospital.
Dr. Judd Jensen described the efforts of Swedish Medical Center, Englewood, Colo. to streamline the emergency care of patients suspected of having an acute ischemic stroke after a task force determined that their previous “sequential, step-by-step process” wasted time. The median DTN time at the hospital’s stroke center had dropped from 46 minutes in 2010 to 39 minutes in 2013, which was better than the national average, “but we felt we could do better,” said Dr. Jensen, a neurologist at the hospital.
The process was modified so that more of the activities take place simultaneously, which includes immediately sending patients for a CT scan before entering the emergency department and administering IV TPA in the CT area to eligible patients, he explained. Previously, these patients were taken to a bed in the ED on arrival, registered, then examined by the emergency physician and neurologist and transported for a CT scan and then transported back to the ED where TPA was administered, if indicated, after several other steps were completed, including interpreting the CT scan, deciding about treatment, acquiring consent, and contacting the pharmacy to mix the TPA.
This process was improved by increasing pre-hospital notification by emergency medical services (EMS) and establishing a “launchpad” area in the back of the ED where the stroke team meets after EMS notification. On arrival, patients are transferred directly to the CT room where they are examined. The pharmacy is instructed to mix the TPA if an ischemic stroke is suspected, and the TPA is brought to the CT room where a stroke neurologist evaluates the CT scan and TPA is administered if indicated.
The impact of the revised process was evaluated in a prospective study of 262 acute ischemic stroke patients who received IV TPA between January 2010 and December 2014 at the hospital. They had a mean age of 73 years, 44% were male, and 84% were white. Their mean initial National Institutes of Health Stroke Scale (NIHSS) score was 12. The median DTN times dropped to a median of 31 minutes in 2014, Dr. Jensen said.
In 2014, almost 50% of the patients received TPA in 30 minutes or less, compared with about 25% in 2011, 2012, and 2013, he added, noting that 11 minutes was the fastest DTN time in 2014. Patients with an excellent discharge modified Rankin Scale (mRS) score (0 or 1) improved from 31% in 2010 and 30% in 2013 to 46% in 2014. During the time period studied, two patients had a symptomatic intracerebral hemorrhage, one in 2010 and another in 2012.
Dr. Jensen described the process as a multidisciplinary team effort, noting that it is important that emergency room physicians feel comfortable with the administration of TPA in the CT scan area, “because it is still their patient being administered a potentially fatal drug outside of the ED.”
At the meeting, Matthew Padrick, a medical student at the University of Virginia, Charlottesville, presented the results of a pilot study that targeted the EMS transport time as an “untapped treatment window” to improve the time to thrombolytic treatment using a low-cost mobile telestroke system to evaluate patients in the ambulance on their way to the hospital.
Because the catchment area covered by UVA includes a large rural area, transport times to the stroke center can be as long as 30 to 60 minutes, Mr. Padrick said.
In the “Improving Treatment with Rapid Evaluation of Acute Stroke via mobile Telemedicine” (iTREAT) study, he and his associates evaluated the feasibility and reliability of performing acute stroke assessments (with the NIHSS) in the ambulance. The iTREAT system, which includes an Apple iPad with retina display attached to the patient stretcher with an extendable clamp, a secure video conferencing application, a high-speed 4G LTE modem, a magnetic antenna on top of the ambulance, and the regional cellular network, “providing seamless connectivity,” he said. At a total cost of under $2,000, the system is designed so that the neurologist can evaluate the patient remotely, via the iPad.
Acting as patients, three medical students were given two unique stroke scenarios each, with stories and specific instructions; vascular neurologists did a face-to-face assessment and a remote iTREAT assessment from the hospital as the students traveled along the major routes to UVA Medical Center. NIHSS scores in the ambulance with the iTREAT system and with face-to-face assessments correlated well, with an overall intraclass correlation of 0.98, Mr. Padrick reported.
The ratings of audio-video quality during the iTREAT evaluations were judged to be ”good” or “excellent” and the NIHSS correlations and audio-video quality ratings improved with time, he added.
“We currently have IRB approval to move forward with real, live patient encounters and we are currently outfitting and training our local EMS agencies” with the system, Mr. Padrick said in an interview after the meeting.
Mr. Padrick has received research support from the American Heart Association. Dr. Judd had nothing to disclose.
AT THE AAN 2015 ANNUAL MEETING
DDW: Statin use associated with significantly lower risk of new-onset IBD
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
AT DDW 2015
Key clinical point: A reduced risk of new onset inflammatory bowel disease (IBD) may be another benefit of statin therapy.
Major finding: A prescription for a statin was associated with about a 40% lower risk of new-onset IBD, an effect that was seen with different statins and only in older people, in a large case-control study.
Data source: The retrospective study evaluated the risk of new-onset Crohn’s disease (CD) and new-onset ulcerative colitis (UC), in about 87,500 patients with a diagnostic code for UC or CD, and controls using a US national medical claims and pharmacy database from 2008-2012.
Disclosures: Dr. Ungaro and his coauthors had no relevant disclosures.
FDA panel says duodenoscope reprocessing needs to be improved
SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that duodenoscopes that are properly cleaned and disinfected based on current recommendations for reprocessing do not provide “reasonable assurance of safety and effectiveness,” at a meeting on May 15.
The Food and Drug Administration held a meeting of the agency’s gastroenterology and urology devices panel on May 14 and 15, to address recent concerns about duodenoscopes and several outbreaks in US hospitals of serious infections associated with these devices, used to perform endoscopic retrograde cholangiopancreatography (ERCP).
“Although the incidence of infections appears to be very low relative to the 500,000 to 600,000 cases of ERCP performed a year, there certainly have been infections traced to scopes despite apparent compliance with recommended guidelines for cleaning and disinfection,” said one of the panelists, Dr. Kenneth McQuaid, chief of gastroenterology, at the Veterans Affairs Medical Center, San Francisco.
More than two-thirds of the panel said that they should start to be sterilized, while others supported the continued use of high-level disinfection, which they believed worked well, if done properly. Most of the panel called for innovations in the design of duodenoscopes that make them easier to clean. However, none of the 16 panelists said that the risks of the duodenoscopes outweighed their benefits and should not be used. Halting the use of ERCP would be “catastrophic,” Dr McQuaid commented, noting that the infection risk is small and the benefits are “incredibly large.”
Other recommendations included ensuring the competency and proper training of the technicians involved in duodenoscope reprocessing and continuing to include manual cleaning of the devices, a step that was necessary, they said.
The panel did not officially vote on any of the questions.
In February 2015, the FDA issued safety alerts about the association with duodenoscopes and the transmission of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices, pointing out to health care professionals that the “complex design” of duodenoscopes “may impede effective reprocessing. Reprocessing is defined by the FDA as “a detailed, multistep process to clean and disinfect or sterilize reusable devices.” In a March 4 update, the agency said that duodenoscope-associated infections had been reported for all three duodenoscope manufacturers in the United States, and on March 26, announced that Olympus had issued new manual reprocessing instructions for its TJF-Q180V duodenoscope, which had been associated with outbreaks, and was being marketed despite not having received clearance by the FDA for marketing (an application for clearance is now under review).
Among the other questions the panel was asked was what information about the risks of infection should be provided to patients before they undergo an ERCP. Dr. Karen Woods, a gastroenterologist at Baylor University, Houston, said that there should be a discussion with patients that there have been infections with highly resistant microorganisms associated with duodenoscopes. They should be informed if infections have occurred at the institution where they will undergo the procedure, and told what is being done about the problem, and this topic should be included in the written informed consent, she added.
From 2010 through 2014, 3,116,900 ERCP procedures were performed in the United States, including 668,800 in 2014, according to the FDA.
Duodenoscope manufacturers were invited to participate in the meeting but did not come, FDA officials said. The panelists had no disclosures related to the content of this meeting.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/ucm2007306.htm.
*CORRECTION 5/17/2015: An earlier version of this story misstated the photo caption information.
SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that duodenoscopes that are properly cleaned and disinfected based on current recommendations for reprocessing do not provide “reasonable assurance of safety and effectiveness,” at a meeting on May 15.
The Food and Drug Administration held a meeting of the agency’s gastroenterology and urology devices panel on May 14 and 15, to address recent concerns about duodenoscopes and several outbreaks in US hospitals of serious infections associated with these devices, used to perform endoscopic retrograde cholangiopancreatography (ERCP).
“Although the incidence of infections appears to be very low relative to the 500,000 to 600,000 cases of ERCP performed a year, there certainly have been infections traced to scopes despite apparent compliance with recommended guidelines for cleaning and disinfection,” said one of the panelists, Dr. Kenneth McQuaid, chief of gastroenterology, at the Veterans Affairs Medical Center, San Francisco.
More than two-thirds of the panel said that they should start to be sterilized, while others supported the continued use of high-level disinfection, which they believed worked well, if done properly. Most of the panel called for innovations in the design of duodenoscopes that make them easier to clean. However, none of the 16 panelists said that the risks of the duodenoscopes outweighed their benefits and should not be used. Halting the use of ERCP would be “catastrophic,” Dr McQuaid commented, noting that the infection risk is small and the benefits are “incredibly large.”
Other recommendations included ensuring the competency and proper training of the technicians involved in duodenoscope reprocessing and continuing to include manual cleaning of the devices, a step that was necessary, they said.
The panel did not officially vote on any of the questions.
In February 2015, the FDA issued safety alerts about the association with duodenoscopes and the transmission of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices, pointing out to health care professionals that the “complex design” of duodenoscopes “may impede effective reprocessing. Reprocessing is defined by the FDA as “a detailed, multistep process to clean and disinfect or sterilize reusable devices.” In a March 4 update, the agency said that duodenoscope-associated infections had been reported for all three duodenoscope manufacturers in the United States, and on March 26, announced that Olympus had issued new manual reprocessing instructions for its TJF-Q180V duodenoscope, which had been associated with outbreaks, and was being marketed despite not having received clearance by the FDA for marketing (an application for clearance is now under review).
Among the other questions the panel was asked was what information about the risks of infection should be provided to patients before they undergo an ERCP. Dr. Karen Woods, a gastroenterologist at Baylor University, Houston, said that there should be a discussion with patients that there have been infections with highly resistant microorganisms associated with duodenoscopes. They should be informed if infections have occurred at the institution where they will undergo the procedure, and told what is being done about the problem, and this topic should be included in the written informed consent, she added.
From 2010 through 2014, 3,116,900 ERCP procedures were performed in the United States, including 668,800 in 2014, according to the FDA.
Duodenoscope manufacturers were invited to participate in the meeting but did not come, FDA officials said. The panelists had no disclosures related to the content of this meeting.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/ucm2007306.htm.
*CORRECTION 5/17/2015: An earlier version of this story misstated the photo caption information.
SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously agreed that duodenoscopes that are properly cleaned and disinfected based on current recommendations for reprocessing do not provide “reasonable assurance of safety and effectiveness,” at a meeting on May 15.
The Food and Drug Administration held a meeting of the agency’s gastroenterology and urology devices panel on May 14 and 15, to address recent concerns about duodenoscopes and several outbreaks in US hospitals of serious infections associated with these devices, used to perform endoscopic retrograde cholangiopancreatography (ERCP).
“Although the incidence of infections appears to be very low relative to the 500,000 to 600,000 cases of ERCP performed a year, there certainly have been infections traced to scopes despite apparent compliance with recommended guidelines for cleaning and disinfection,” said one of the panelists, Dr. Kenneth McQuaid, chief of gastroenterology, at the Veterans Affairs Medical Center, San Francisco.
More than two-thirds of the panel said that they should start to be sterilized, while others supported the continued use of high-level disinfection, which they believed worked well, if done properly. Most of the panel called for innovations in the design of duodenoscopes that make them easier to clean. However, none of the 16 panelists said that the risks of the duodenoscopes outweighed their benefits and should not be used. Halting the use of ERCP would be “catastrophic,” Dr McQuaid commented, noting that the infection risk is small and the benefits are “incredibly large.”
Other recommendations included ensuring the competency and proper training of the technicians involved in duodenoscope reprocessing and continuing to include manual cleaning of the devices, a step that was necessary, they said.
The panel did not officially vote on any of the questions.
In February 2015, the FDA issued safety alerts about the association with duodenoscopes and the transmission of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices, pointing out to health care professionals that the “complex design” of duodenoscopes “may impede effective reprocessing. Reprocessing is defined by the FDA as “a detailed, multistep process to clean and disinfect or sterilize reusable devices.” In a March 4 update, the agency said that duodenoscope-associated infections had been reported for all three duodenoscope manufacturers in the United States, and on March 26, announced that Olympus had issued new manual reprocessing instructions for its TJF-Q180V duodenoscope, which had been associated with outbreaks, and was being marketed despite not having received clearance by the FDA for marketing (an application for clearance is now under review).
Among the other questions the panel was asked was what information about the risks of infection should be provided to patients before they undergo an ERCP. Dr. Karen Woods, a gastroenterologist at Baylor University, Houston, said that there should be a discussion with patients that there have been infections with highly resistant microorganisms associated with duodenoscopes. They should be informed if infections have occurred at the institution where they will undergo the procedure, and told what is being done about the problem, and this topic should be included in the written informed consent, she added.
From 2010 through 2014, 3,116,900 ERCP procedures were performed in the United States, including 668,800 in 2014, according to the FDA.
Duodenoscope manufacturers were invited to participate in the meeting but did not come, FDA officials said. The panelists had no disclosures related to the content of this meeting.
Any infections possibly related to duodenoscopes should be reported to the manufacturer and the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/ucm2007306.htm.
*CORRECTION 5/17/2015: An earlier version of this story misstated the photo caption information.
AT AN FDA ADVISORY COMMITTEE MEETING
FDA panel supports approval of combination drug for cystic fibrosis
GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.
At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.
Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.
In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.
The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).
At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.
Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.
Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV1 over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.
If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.
About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.
GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.
At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.
Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.
In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.
The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).
At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.
Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.
Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV1 over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.
If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.
About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.
GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.
At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.
Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.
In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.
The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).
At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.
Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.
Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV1 over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.
If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.
About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.
AT AN FDA ADVISORY COMMITTEE MEETING
AAN: Scheduled daily DBS effective in small Tourette syndrome study
WASHINGTON – Scheduled administration of bilateral deep brain stimulation of the centromedian thalamus for less than 2 hours a day resulted in a significant reduction in tics in several patients with Tourette syndrome over 2 years in a proof-of-concept study presented at the annual meeting of the American Academy of Neurology.
Of the four patients who completed the 24-month study, three experienced significant improvements, said Justin Rossi, an MD-PhD candidate at the University of Florida in Gainesville.
Instead of using the standard continuous deep brain stimulation (DBS), Mr. Rossi and colleagues at the university's Center for Movement Disorders and Neurorestoration evaluated a scheduled, personalized stimulation approach, with stimulation of the centromedian thalamus (bilaterally) tailored to the times of the day when patients experienced the most sequelae from the tics, such as when they were driving, exercising, or working, and when the intensity of the tics was the greatest.
The rationale for investigating this approach is that instead of using the “classical continuous approach” to DBS, a tailored approach might be effective in these patients, with the potential benefits of increasing battery life (and delaying another surgical procedure to replace the battery) and reducing side effects associated with stimulation, Mr. Rossi said.
Many studies have found that DBS is effective in “select medication-refractory cases of Tourette syndrome,” he noted. “However, in contrast to Parkinson’s disease, essential tremor, and other movement disorders for which DBS has been commonly used as a therapy, Tourette syndrome is a paroxysmal disorder,” and the frequency of tics can vary from patient to patient, with individual patients reporting that the intensity of tics “waxes and wanes throughout the day, often predictably.”
The study enrolled five patients; responses were evaluated with two rating scales, the Yale Global Tic Severity Scale (YGTSS) and the Modified Rush Video-Based Tic Rating Scale (MRTRS). A patient was considered a responder if there was more than a 40% improvement in the YGTSS or MRTRS from the preoperative baseline level, at 24 months, the primary outcome. (One patient was lost to follow-up after 18 months because the center was too far away.) Patients had the opportunity to modify the schedule at each 6-month visit.
At 24 months, the YGTSS total scores improved by 46%, 58%, and 17% and the MRTRS total scores improved by 79%, 81%, and 44% in the three responders. These patients had a mean stimulation time of 1.85 hours a day, ranging from 47 to 186 minutes per day. The one patient who did not meet the primary endpoint – with a 10% response on the YGTSS and a 21% response in the MRTRS – had the greatest amount of stimulation per day (4 hours a day). At 24 months, the responders had statistically significant improvements from baseline in components of the two scales, including the number of phonic tics per minute, motor tic severity, and phonic tic severity, Mr. Rossi said.
This is a proof-of-concept study and the results and conclusions are preliminary, but the results “warrant larger studies,” he concluded.
More research is needed to understand this mechanism on a more physiological level, which is being pursued at his center, he added. The results shed some light on whether the mechanism of DBS in Tourette syndrome is a cumulative effect of stimulation over time or whether DBS has an effect around the time the tics occur, and these results support the latter explanation, Mr. Rossi speculated.
He had no disclosures. The study was sponsored by the National Institutes of Health.
WASHINGTON – Scheduled administration of bilateral deep brain stimulation of the centromedian thalamus for less than 2 hours a day resulted in a significant reduction in tics in several patients with Tourette syndrome over 2 years in a proof-of-concept study presented at the annual meeting of the American Academy of Neurology.
Of the four patients who completed the 24-month study, three experienced significant improvements, said Justin Rossi, an MD-PhD candidate at the University of Florida in Gainesville.
Instead of using the standard continuous deep brain stimulation (DBS), Mr. Rossi and colleagues at the university's Center for Movement Disorders and Neurorestoration evaluated a scheduled, personalized stimulation approach, with stimulation of the centromedian thalamus (bilaterally) tailored to the times of the day when patients experienced the most sequelae from the tics, such as when they were driving, exercising, or working, and when the intensity of the tics was the greatest.
The rationale for investigating this approach is that instead of using the “classical continuous approach” to DBS, a tailored approach might be effective in these patients, with the potential benefits of increasing battery life (and delaying another surgical procedure to replace the battery) and reducing side effects associated with stimulation, Mr. Rossi said.
Many studies have found that DBS is effective in “select medication-refractory cases of Tourette syndrome,” he noted. “However, in contrast to Parkinson’s disease, essential tremor, and other movement disorders for which DBS has been commonly used as a therapy, Tourette syndrome is a paroxysmal disorder,” and the frequency of tics can vary from patient to patient, with individual patients reporting that the intensity of tics “waxes and wanes throughout the day, often predictably.”
The study enrolled five patients; responses were evaluated with two rating scales, the Yale Global Tic Severity Scale (YGTSS) and the Modified Rush Video-Based Tic Rating Scale (MRTRS). A patient was considered a responder if there was more than a 40% improvement in the YGTSS or MRTRS from the preoperative baseline level, at 24 months, the primary outcome. (One patient was lost to follow-up after 18 months because the center was too far away.) Patients had the opportunity to modify the schedule at each 6-month visit.
At 24 months, the YGTSS total scores improved by 46%, 58%, and 17% and the MRTRS total scores improved by 79%, 81%, and 44% in the three responders. These patients had a mean stimulation time of 1.85 hours a day, ranging from 47 to 186 minutes per day. The one patient who did not meet the primary endpoint – with a 10% response on the YGTSS and a 21% response in the MRTRS – had the greatest amount of stimulation per day (4 hours a day). At 24 months, the responders had statistically significant improvements from baseline in components of the two scales, including the number of phonic tics per minute, motor tic severity, and phonic tic severity, Mr. Rossi said.
This is a proof-of-concept study and the results and conclusions are preliminary, but the results “warrant larger studies,” he concluded.
More research is needed to understand this mechanism on a more physiological level, which is being pursued at his center, he added. The results shed some light on whether the mechanism of DBS in Tourette syndrome is a cumulative effect of stimulation over time or whether DBS has an effect around the time the tics occur, and these results support the latter explanation, Mr. Rossi speculated.
He had no disclosures. The study was sponsored by the National Institutes of Health.
WASHINGTON – Scheduled administration of bilateral deep brain stimulation of the centromedian thalamus for less than 2 hours a day resulted in a significant reduction in tics in several patients with Tourette syndrome over 2 years in a proof-of-concept study presented at the annual meeting of the American Academy of Neurology.
Of the four patients who completed the 24-month study, three experienced significant improvements, said Justin Rossi, an MD-PhD candidate at the University of Florida in Gainesville.
Instead of using the standard continuous deep brain stimulation (DBS), Mr. Rossi and colleagues at the university's Center for Movement Disorders and Neurorestoration evaluated a scheduled, personalized stimulation approach, with stimulation of the centromedian thalamus (bilaterally) tailored to the times of the day when patients experienced the most sequelae from the tics, such as when they were driving, exercising, or working, and when the intensity of the tics was the greatest.
The rationale for investigating this approach is that instead of using the “classical continuous approach” to DBS, a tailored approach might be effective in these patients, with the potential benefits of increasing battery life (and delaying another surgical procedure to replace the battery) and reducing side effects associated with stimulation, Mr. Rossi said.
Many studies have found that DBS is effective in “select medication-refractory cases of Tourette syndrome,” he noted. “However, in contrast to Parkinson’s disease, essential tremor, and other movement disorders for which DBS has been commonly used as a therapy, Tourette syndrome is a paroxysmal disorder,” and the frequency of tics can vary from patient to patient, with individual patients reporting that the intensity of tics “waxes and wanes throughout the day, often predictably.”
The study enrolled five patients; responses were evaluated with two rating scales, the Yale Global Tic Severity Scale (YGTSS) and the Modified Rush Video-Based Tic Rating Scale (MRTRS). A patient was considered a responder if there was more than a 40% improvement in the YGTSS or MRTRS from the preoperative baseline level, at 24 months, the primary outcome. (One patient was lost to follow-up after 18 months because the center was too far away.) Patients had the opportunity to modify the schedule at each 6-month visit.
At 24 months, the YGTSS total scores improved by 46%, 58%, and 17% and the MRTRS total scores improved by 79%, 81%, and 44% in the three responders. These patients had a mean stimulation time of 1.85 hours a day, ranging from 47 to 186 minutes per day. The one patient who did not meet the primary endpoint – with a 10% response on the YGTSS and a 21% response in the MRTRS – had the greatest amount of stimulation per day (4 hours a day). At 24 months, the responders had statistically significant improvements from baseline in components of the two scales, including the number of phonic tics per minute, motor tic severity, and phonic tic severity, Mr. Rossi said.
This is a proof-of-concept study and the results and conclusions are preliminary, but the results “warrant larger studies,” he concluded.
More research is needed to understand this mechanism on a more physiological level, which is being pursued at his center, he added. The results shed some light on whether the mechanism of DBS in Tourette syndrome is a cumulative effect of stimulation over time or whether DBS has an effect around the time the tics occur, and these results support the latter explanation, Mr. Rossi speculated.
He had no disclosures. The study was sponsored by the National Institutes of Health.
AT THE AAN 2015 ANNUAL MEETING
Key clinical point: Promising results of a tailored approach to deep brain stimulation in three patients with Tourette syndrome merits a larger trial.
Major finding: In three of the four patients who completed the study, DBS of the centromedian thalamus for less than 2 hours a day resulted in significant improvements over 24 months.
Data source: A proof-of-concept study in five patients with Tourette syndrome, evaluating DBS of the centromedian thalamus, scheduled for times when tics interfered with activities or were most intense.
Disclosures: The National Institutes of Health sponsored the study. Mr. Rossi had no disclosures.
AAN: Largest neuroleptic malignant syndrome study finds predictors of poor outcome
WASHINGTON – Older age was a significant predictor of a poor outcome associated with neuroleptic malignant syndrome in a retrospective review of more than 1,700 inpatient cases in the United States over a recent 12-year period.
Other factors that were significant positive predictors of a poor outcome were acute kidney injury, respiratory failure, and seizures, Dr. Sumul Modi said at the annual meeting of the American Academy of Neurology. The study also showed that inpatient mortality due to neuroleptic malignant syndrome (NMS) has significantly dropped since it was first described in 1960. Because NMS is rare, it is difficult to study a large sample of patients, and large real-world studies of NMS are lacking, especially in the last few decades, he said, noting that most of the literature on NMS is from the 20th century.
The aim of this study was to identify predictors of poor outcome associated with NMS, using the National Inpatient Sample, a large, publicly available, all-payer, inpatient health care database that covers about 20% of all admissions to nonfederal hospitals in the United States. ICD-9 diagnostic and procedure were used to identify major complications and procedures. Univariate and multivariate logistic regression analyses were used to identify predictors.
From 2000 through 2011, Dr. Modi, a neurology resident at Henry Ford Hospital, Detroit, and his coauthor identified 1,725 cases in the database with a primary diagnosis of NMS in patients aged 16 and older, making this the largest study of NMS to date. (Cases with a secondary diagnosis that can affect the diagnosis of NMS, including serotonin syndrome and substance abuse, alcohol, or drug withdrawal, were excluded.)
Of these patients, 183 – almost 11% – had a poor outcome, defined as in-hospital death or having undergone a feeding tube placement. Of the total, 99 patients – almost 6% – died while hospitalized.
The most common complication associated with NMS was rhabdomyolysis, in 24%, which was not directly associated with a poor outcome. But other complications – seizures (12.9% of the total), acute kidney injury (15.7%), respiratory failure (11.4%), and cardiac dysrhythmia (8.8%) – were also significantly associated with poor outcome, Dr. Modi said.
Medical complications significantly associated with a poor outcome included pneumonia (reported in 8.5% of the patients with NMS), urinary tract infection (18%), sepsis (6.3%), and acute liver failure (1.3%).
A multivariate analysis, with adjusted odds ratios, determined that the following were predictors of poor outcome: age (OR, 1.5), acute kidney injury (OR, 2.1), acute respiratory failure (OR, 10.7), and seizures (OR, 1.7).
Every calendar year increase was a “small but significant” negative predictor of poor outcome (OR, 0.9). During the period studied, the highest mortality rate – about 9% – was in 2002, dropping to about 2.5% in 2009 and increasing to about 5% in 2010 and 2011. The marked drop in mortality since NMS was first described in 1960 could be due to improved intensive care, but could also be related to the various treatment approaches used, such as dantrolene and dopamine agonists, Dr. Modi said.
Increasing use of atypical antipsychotics may also play a role, but the investigators were not able to determine if patients had been treated with an atypical or typical antipsychotic and what treatments were used to manage NMS, which are limitations of the study, he said. They were also not able to determine if the time to diagnosis played a role in the outcome or whether patients were treated in a tertiary medical center.
Dr. Modi and his coauthor had no disclosures.
WASHINGTON – Older age was a significant predictor of a poor outcome associated with neuroleptic malignant syndrome in a retrospective review of more than 1,700 inpatient cases in the United States over a recent 12-year period.
Other factors that were significant positive predictors of a poor outcome were acute kidney injury, respiratory failure, and seizures, Dr. Sumul Modi said at the annual meeting of the American Academy of Neurology. The study also showed that inpatient mortality due to neuroleptic malignant syndrome (NMS) has significantly dropped since it was first described in 1960. Because NMS is rare, it is difficult to study a large sample of patients, and large real-world studies of NMS are lacking, especially in the last few decades, he said, noting that most of the literature on NMS is from the 20th century.
The aim of this study was to identify predictors of poor outcome associated with NMS, using the National Inpatient Sample, a large, publicly available, all-payer, inpatient health care database that covers about 20% of all admissions to nonfederal hospitals in the United States. ICD-9 diagnostic and procedure were used to identify major complications and procedures. Univariate and multivariate logistic regression analyses were used to identify predictors.
From 2000 through 2011, Dr. Modi, a neurology resident at Henry Ford Hospital, Detroit, and his coauthor identified 1,725 cases in the database with a primary diagnosis of NMS in patients aged 16 and older, making this the largest study of NMS to date. (Cases with a secondary diagnosis that can affect the diagnosis of NMS, including serotonin syndrome and substance abuse, alcohol, or drug withdrawal, were excluded.)
Of these patients, 183 – almost 11% – had a poor outcome, defined as in-hospital death or having undergone a feeding tube placement. Of the total, 99 patients – almost 6% – died while hospitalized.
The most common complication associated with NMS was rhabdomyolysis, in 24%, which was not directly associated with a poor outcome. But other complications – seizures (12.9% of the total), acute kidney injury (15.7%), respiratory failure (11.4%), and cardiac dysrhythmia (8.8%) – were also significantly associated with poor outcome, Dr. Modi said.
Medical complications significantly associated with a poor outcome included pneumonia (reported in 8.5% of the patients with NMS), urinary tract infection (18%), sepsis (6.3%), and acute liver failure (1.3%).
A multivariate analysis, with adjusted odds ratios, determined that the following were predictors of poor outcome: age (OR, 1.5), acute kidney injury (OR, 2.1), acute respiratory failure (OR, 10.7), and seizures (OR, 1.7).
Every calendar year increase was a “small but significant” negative predictor of poor outcome (OR, 0.9). During the period studied, the highest mortality rate – about 9% – was in 2002, dropping to about 2.5% in 2009 and increasing to about 5% in 2010 and 2011. The marked drop in mortality since NMS was first described in 1960 could be due to improved intensive care, but could also be related to the various treatment approaches used, such as dantrolene and dopamine agonists, Dr. Modi said.
Increasing use of atypical antipsychotics may also play a role, but the investigators were not able to determine if patients had been treated with an atypical or typical antipsychotic and what treatments were used to manage NMS, which are limitations of the study, he said. They were also not able to determine if the time to diagnosis played a role in the outcome or whether patients were treated in a tertiary medical center.
Dr. Modi and his coauthor had no disclosures.
WASHINGTON – Older age was a significant predictor of a poor outcome associated with neuroleptic malignant syndrome in a retrospective review of more than 1,700 inpatient cases in the United States over a recent 12-year period.
Other factors that were significant positive predictors of a poor outcome were acute kidney injury, respiratory failure, and seizures, Dr. Sumul Modi said at the annual meeting of the American Academy of Neurology. The study also showed that inpatient mortality due to neuroleptic malignant syndrome (NMS) has significantly dropped since it was first described in 1960. Because NMS is rare, it is difficult to study a large sample of patients, and large real-world studies of NMS are lacking, especially in the last few decades, he said, noting that most of the literature on NMS is from the 20th century.
The aim of this study was to identify predictors of poor outcome associated with NMS, using the National Inpatient Sample, a large, publicly available, all-payer, inpatient health care database that covers about 20% of all admissions to nonfederal hospitals in the United States. ICD-9 diagnostic and procedure were used to identify major complications and procedures. Univariate and multivariate logistic regression analyses were used to identify predictors.
From 2000 through 2011, Dr. Modi, a neurology resident at Henry Ford Hospital, Detroit, and his coauthor identified 1,725 cases in the database with a primary diagnosis of NMS in patients aged 16 and older, making this the largest study of NMS to date. (Cases with a secondary diagnosis that can affect the diagnosis of NMS, including serotonin syndrome and substance abuse, alcohol, or drug withdrawal, were excluded.)
Of these patients, 183 – almost 11% – had a poor outcome, defined as in-hospital death or having undergone a feeding tube placement. Of the total, 99 patients – almost 6% – died while hospitalized.
The most common complication associated with NMS was rhabdomyolysis, in 24%, which was not directly associated with a poor outcome. But other complications – seizures (12.9% of the total), acute kidney injury (15.7%), respiratory failure (11.4%), and cardiac dysrhythmia (8.8%) – were also significantly associated with poor outcome, Dr. Modi said.
Medical complications significantly associated with a poor outcome included pneumonia (reported in 8.5% of the patients with NMS), urinary tract infection (18%), sepsis (6.3%), and acute liver failure (1.3%).
A multivariate analysis, with adjusted odds ratios, determined that the following were predictors of poor outcome: age (OR, 1.5), acute kidney injury (OR, 2.1), acute respiratory failure (OR, 10.7), and seizures (OR, 1.7).
Every calendar year increase was a “small but significant” negative predictor of poor outcome (OR, 0.9). During the period studied, the highest mortality rate – about 9% – was in 2002, dropping to about 2.5% in 2009 and increasing to about 5% in 2010 and 2011. The marked drop in mortality since NMS was first described in 1960 could be due to improved intensive care, but could also be related to the various treatment approaches used, such as dantrolene and dopamine agonists, Dr. Modi said.
Increasing use of atypical antipsychotics may also play a role, but the investigators were not able to determine if patients had been treated with an atypical or typical antipsychotic and what treatments were used to manage NMS, which are limitations of the study, he said. They were also not able to determine if the time to diagnosis played a role in the outcome or whether patients were treated in a tertiary medical center.
Dr. Modi and his coauthor had no disclosures.
AT THE AAN 2015 ANNUAL MEETING
Key clinical point: Patients diagnosed with neuroleptic malignant syndrome may be at increased risk of a poor outcome if they are older and have seizures, respiratory failure, or acute kidney injury while hospitalized.
Major finding: A poor outcome was independently predicted by age (OR, 1.5), acute kidney injury (OR, 2.1), acute respiratory failure (OR, 10.7), and seizures (OR, 1.7).
Data source: The retrospective study evaluated 1,725 NMS cases in the National Inpatient Sample.
Disclosures: Dr. Modi and his coauthor had no disclosures.
AAN: Study supports safety of fingolimod for MS
WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.
The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.
He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).
The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.
The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.
In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 109/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.
The overall rate of infections did not appear to increase over time, with an IRR of 0.72.
There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 109/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.
Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”
Dr. Cohen disclosed ties with Novartis, which funded the study.
WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.
The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.
He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).
The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.
The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.
In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 109/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.
The overall rate of infections did not appear to increase over time, with an IRR of 0.72.
There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 109/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.
Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”
Dr. Cohen disclosed ties with Novartis, which funded the study.
WASHINGTON – An analysis of long-term safety data of fingolimod in patients with relapsing multiple sclerosis treated for as long as 7 years has not identified new safety issues or increases in any known adverse events identified in the core studies conducted before approval, Dr. Jeffrey Cohen reported at the annual meeting of the American Academy of Neurology.
The results, based on data from the ongoing LONGTERMS open-label extension study following the safety and tolerability of fingolimod in patients enrolled in phase II and III trials, confirm that the treatment is “suitable” for long-term therapy for patients with relapsing MS, said Dr. Cohen, director of the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
Fingolimod, a sphingosine 1-phosphate receptor modulator marketed as Gilenya, was approved by the Food and Drug Administration in 2010 for relapsing forms of MS at a dose of 0.5 mg taken orally once a day. As of November 2014, more than 114,000 people worldwide have been treated with fingolimod, representing more than 195,000 patient-years of exposure, according to Dr. Cohen, who cited data from Novartis, the manufacturer.
He presented the results of the analysis of adverse events (AEs), serious adverse events (SAEs), and AEs of “special interest,” among 1,655 people with relapsing-remitting MS enrolled in LONGTERMS who were treated with fingolimod (0.5 mg a day) for a mean of 4 years (839 were on treatment for at least 7 years). They included 1,212 people treated with fingolimod in the core studies, as well as people in those studies who were on placebo or a comparator treatment and were rerandomized to treatment with fingolimod. At enrollment in the original study, the mean age was 38 years, and 70% of the patients were females. The patients had had MS for a mean of 5 years, and had a mean score of 2.31 on the Expanded Disability Status Scale (EDSS).
The analysis compared the safety profile in the extension and core studies by calculating the incidence rate (IR) for the events in each database, and calculating the incidence rate ratio (IRR) by dividing the IR for the longterm study cohort by the IR for the core cohort. (The IRs were expressed as the number of AEs “per 100 patient-years of the at-risk population.”) AEs of special interest were infections, hypertension, respiratory conditions, lymphopenia, macular edema, bradyarrhythmia after the first dose, reproductive toxicity, liver transaminase elevation, skin cancer, other malignant neoplasms, and thromboembolic events.
The only SAE with an IRR that exceeded 1 was herpes zoster infections, but the odds ratio was broad and overlapped one, Dr. Cohen said. The results for other SAEs included an IRR of 0.47 for bradyarrhythmia after the first dose, and an IRR of 0.45 for macular edema.
In the analysis of AEs, leucopenia and lymphopenia “seem to be increased” with more time on fingolimod, he noted. In the long-term cohort, the IR for this adverse event was 6.2, compared with 4.6 for the core cohort, for an IRR of 1.36. However, this could have been a result of increased reporting resulting from investigators’ awareness of lymphocyte counts, since it is an open-label study, he said, pointing out that in the core studies, lymphocyte counts were unblinded only if they reached 0.2 x 109/L. There was no evidence of a progressive decline in lymphocyte counts, with no significant differences in trends over time with mean lymphocyte counts between those in the core and extension studies, although “we can’t eliminate” this possibility, he added.
The overall rate of infections did not appear to increase over time, with an IRR of 0.72.
There were more serious infections with longer treatment among patients with sustained low levels of peripheral lymphocyte counts, defined as absolute lymphocyte counts below 0.4 x 109/L for at least 60% of the records during the corresponding time interval. There were 28 cases of serious infection among those on treatment for more than 2 years and 14 cases among those on treatment for 2 years or less. The occurrence rate for the number of serious infections, which could be more than once for an individual patient, was 1.4 among those treated for more than 2 years vs. 1.0 for those treated for 2 years or less, for an occurrence rate ratio of 1.47.
Pointing out that the number of cases was small and the confidence intervals for this finding were wide, Dr. Cohen concluded that the LONGTERMS data do not support “an overall increased risk of infections with long-term exposure or with sustained low peripheral lymphocyte counts.”
Dr. Cohen disclosed ties with Novartis, which funded the study.
AT THE AAN 2015 ANNUAL MEETING
Key clinical point: Results of an ongoing study support the safety of fingolimod for long-term treatment of patients with relapsing-remitting multiple sclerosis.
Major finding: A comparison between preapproval studies and a large long-term extension study of patients with MS did not identify any increase in known safety issues or new safety issues associated with fingolimod.
Data source: Study of more than 1,655 people with relapsing-remitting MS who have been treated with fingolimod for a mean of 4 years.
Disclosures: Dr. Cohen disclosed ties with Novartis, which funded the study.
