The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

Ticagrelor was found to be “not superior” to clopidogrel at preventing cardiovascular events in the largest clinical trial to date involving patients with symptomatic peripheral artery disease (PAD), Manesh Patel, MD, reported at the American Heart Association scientific sessions.*

Ticagrelor also was no better than clopidogrel at preventing acute limb ischemia in this study of 13,885 patients.

Regarding safety issues, the two drugs had identical rates of major bleeding adverse events, but ticagrelor was discontinued significantly more often than clopidogrel was, because of its other well-known adverse effects, said Dr. Patel of Duke University, Durham, N.C.

The findings of the EUCLID (Examining the Use of Ticagrelor in PAD) study were presented at the meeting and simultaneously published online Nov. 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMoa1611688).

In addition, the results of a substudy of the EUCLID trial involving the 7,875 participants who had previously undergone lower-limb revascularization were reported at the meeting and simultaneously published online in Circulation (2016 Nov 13; doi: 10.1161/CIRCULATIONAHA.116.025880).

Until now, there have been no large studies comparing antiplatelet therapies in patients with PAD. Clopidogrel is considered superior to aspirin in this patient population based on limited evidence, often extrapolated from studies of acute coronary syndromes or coronary artery disease. Ticagrelor also proved beneficial in these contexts, so researchers performed the EUCLID study, comparing the two medications head to head in patients with PAD.

The manufacturer-funded double-blind trial was conducted at 811 medical centers in eight countries. Patients aged 50 years or older (median age, 66 years) were randomly assigned to receive either oral ticagrelor, 90 mg twice daily (6,930 patients), or oral clopidogrel, 75 mg once daily (6,955 patients), and were followed for a median of 30 months.

The primary efficacy endpoint – the first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred in 10.8% of the ticagrelor group and 10.6% of the clopidogrel group, for a hazard ratio of 1.02.

When the components of this composite endpoint were considered individually, only the rate of ischemic stroke was significantly different between the two study groups, occurring in 1.9% of patients taking ticagrelor and 2.4% of those taking clopidogrel (HR, 0.78).

Other important secondary and composite efficacy endpoints, including acute limb ischemia and revascularization, were similar between the two study groups, Dr. Patel said.

The primary safety endpoint – the rate of major bleeding events – occurred in the same percentage of both study groups (1.6%), and individual rates of fatal bleeding, intracranial bleeding, and minor bleeding were similar.

“There were numerically fewer fatal bleeding events in the ticagrelor group than in the clopidogrel group (10 vs. 20), but there were significantly more bleeding events leading to drug discontinuation with ticagrelor than with clopidogrel (168 vs. 112),” he noted.

Ticagrelor was discontinued more often than clopidogrel during the study (30.1% of patients vs. 25.9%; HR, 1.21). Discontinuation was driven mainly by the occurrence of dyspnea (4.8% vs. 0.8%) and minor bleeding, both of which are well-described adverse effects of ticagrelor, Dr. Patel said.

“Our findings show the hazards of extrapolating evidence from patients with coronary artery disease to those with peripheral artery disease,” he added.

In a separate report in Circulation, the results were similar in the substudy of EUCLID participants who had already undergone lower-extremity revascularization procedures before enrollment, reported W. Schuyler Jones, MD, also of of Duke University.

The primary efficacy endpoint occurred in 11.4% of the ticagrelor group and 11.3% of the clopidogrel group, a nonsignificant difference (HR, 1.01). “Other key secondary and composite endpoints, including repeat revascularization, also were not different between the two study groups,” Dr. Jones said.

Regarding safety endpoints, the rates of major bleeding, fatal bleeding, intracranial bleeding, and minor bleeding all were similar between the two study groups.

“These findings suggest that patients with prior revascularization have a substantial residual rate of cardiovascular and acute limb events, despite high adherence to antiplatelet and statin medications, and require further study,” Dr. Jones noted.

*Correction 11/14/16: An earlier version of this article misstated the name of the investigator who presented the study at the meeting.

Ticagrelor was found to be “not superior” to clopidogrel at preventing cardiovascular events in the largest clinical trial to date involving patients with symptomatic peripheral artery disease (PAD), Manesh Patel, MD, reported at the American Heart Association scientific sessions.*

Ticagrelor also was no better than clopidogrel at preventing acute limb ischemia in this study of 13,885 patients.

Regarding safety issues, the two drugs had identical rates of major bleeding adverse events, but ticagrelor was discontinued significantly more often than clopidogrel was, because of its other well-known adverse effects, said Dr. Patel of Duke University, Durham, N.C.

The findings of the EUCLID (Examining the Use of Ticagrelor in PAD) study were presented at the meeting and simultaneously published online Nov. 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMoa1611688).

In addition, the results of a substudy of the EUCLID trial involving the 7,875 participants who had previously undergone lower-limb revascularization were reported at the meeting and simultaneously published online in Circulation (2016 Nov 13; doi: 10.1161/CIRCULATIONAHA.116.025880).

Until now, there have been no large studies comparing antiplatelet therapies in patients with PAD. Clopidogrel is considered superior to aspirin in this patient population based on limited evidence, often extrapolated from studies of acute coronary syndromes or coronary artery disease. Ticagrelor also proved beneficial in these contexts, so researchers performed the EUCLID study, comparing the two medications head to head in patients with PAD.

The manufacturer-funded double-blind trial was conducted at 811 medical centers in eight countries. Patients aged 50 years or older (median age, 66 years) were randomly assigned to receive either oral ticagrelor, 90 mg twice daily (6,930 patients), or oral clopidogrel, 75 mg once daily (6,955 patients), and were followed for a median of 30 months.

The primary efficacy endpoint – the first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred in 10.8% of the ticagrelor group and 10.6% of the clopidogrel group, for a hazard ratio of 1.02.

When the components of this composite endpoint were considered individually, only the rate of ischemic stroke was significantly different between the two study groups, occurring in 1.9% of patients taking ticagrelor and 2.4% of those taking clopidogrel (HR, 0.78).

Other important secondary and composite efficacy endpoints, including acute limb ischemia and revascularization, were similar between the two study groups, Dr. Patel said.

The primary safety endpoint – the rate of major bleeding events – occurred in the same percentage of both study groups (1.6%), and individual rates of fatal bleeding, intracranial bleeding, and minor bleeding were similar.

“There were numerically fewer fatal bleeding events in the ticagrelor group than in the clopidogrel group (10 vs. 20), but there were significantly more bleeding events leading to drug discontinuation with ticagrelor than with clopidogrel (168 vs. 112),” he noted.

Ticagrelor was discontinued more often than clopidogrel during the study (30.1% of patients vs. 25.9%; HR, 1.21). Discontinuation was driven mainly by the occurrence of dyspnea (4.8% vs. 0.8%) and minor bleeding, both of which are well-described adverse effects of ticagrelor, Dr. Patel said.

“Our findings show the hazards of extrapolating evidence from patients with coronary artery disease to those with peripheral artery disease,” he added.

In a separate report in Circulation, the results were similar in the substudy of EUCLID participants who had already undergone lower-extremity revascularization procedures before enrollment, reported W. Schuyler Jones, MD, also of of Duke University.

The primary efficacy endpoint occurred in 11.4% of the ticagrelor group and 11.3% of the clopidogrel group, a nonsignificant difference (HR, 1.01). “Other key secondary and composite endpoints, including repeat revascularization, also were not different between the two study groups,” Dr. Jones said.

Regarding safety endpoints, the rates of major bleeding, fatal bleeding, intracranial bleeding, and minor bleeding all were similar between the two study groups.

“These findings suggest that patients with prior revascularization have a substantial residual rate of cardiovascular and acute limb events, despite high adherence to antiplatelet and statin medications, and require further study,” Dr. Jones noted.

*Correction 11/14/16: An earlier version of this article misstated the name of the investigator who presented the study at the meeting.

Ticagrelor was found to be “not superior” to clopidogrel at preventing cardiovascular events in the largest clinical trial to date involving patients with symptomatic peripheral artery disease (PAD), Manesh Patel, MD, reported at the American Heart Association scientific sessions.*

Ticagrelor also was no better than clopidogrel at preventing acute limb ischemia in this study of 13,885 patients.

Regarding safety issues, the two drugs had identical rates of major bleeding adverse events, but ticagrelor was discontinued significantly more often than clopidogrel was, because of its other well-known adverse effects, said Dr. Patel of Duke University, Durham, N.C.

The findings of the EUCLID (Examining the Use of Ticagrelor in PAD) study were presented at the meeting and simultaneously published online Nov. 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMoa1611688).

In addition, the results of a substudy of the EUCLID trial involving the 7,875 participants who had previously undergone lower-limb revascularization were reported at the meeting and simultaneously published online in Circulation (2016 Nov 13; doi: 10.1161/CIRCULATIONAHA.116.025880).

Until now, there have been no large studies comparing antiplatelet therapies in patients with PAD. Clopidogrel is considered superior to aspirin in this patient population based on limited evidence, often extrapolated from studies of acute coronary syndromes or coronary artery disease. Ticagrelor also proved beneficial in these contexts, so researchers performed the EUCLID study, comparing the two medications head to head in patients with PAD.

The manufacturer-funded double-blind trial was conducted at 811 medical centers in eight countries. Patients aged 50 years or older (median age, 66 years) were randomly assigned to receive either oral ticagrelor, 90 mg twice daily (6,930 patients), or oral clopidogrel, 75 mg once daily (6,955 patients), and were followed for a median of 30 months.

The primary efficacy endpoint – the first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred in 10.8% of the ticagrelor group and 10.6% of the clopidogrel group, for a hazard ratio of 1.02.

When the components of this composite endpoint were considered individually, only the rate of ischemic stroke was significantly different between the two study groups, occurring in 1.9% of patients taking ticagrelor and 2.4% of those taking clopidogrel (HR, 0.78).

Other important secondary and composite efficacy endpoints, including acute limb ischemia and revascularization, were similar between the two study groups, Dr. Patel said.

The primary safety endpoint – the rate of major bleeding events – occurred in the same percentage of both study groups (1.6%), and individual rates of fatal bleeding, intracranial bleeding, and minor bleeding were similar.

“There were numerically fewer fatal bleeding events in the ticagrelor group than in the clopidogrel group (10 vs. 20), but there were significantly more bleeding events leading to drug discontinuation with ticagrelor than with clopidogrel (168 vs. 112),” he noted.

Ticagrelor was discontinued more often than clopidogrel during the study (30.1% of patients vs. 25.9%; HR, 1.21). Discontinuation was driven mainly by the occurrence of dyspnea (4.8% vs. 0.8%) and minor bleeding, both of which are well-described adverse effects of ticagrelor, Dr. Patel said.

“Our findings show the hazards of extrapolating evidence from patients with coronary artery disease to those with peripheral artery disease,” he added.

In a separate report in Circulation, the results were similar in the substudy of EUCLID participants who had already undergone lower-extremity revascularization procedures before enrollment, reported W. Schuyler Jones, MD, also of of Duke University.

The primary efficacy endpoint occurred in 11.4% of the ticagrelor group and 11.3% of the clopidogrel group, a nonsignificant difference (HR, 1.01). “Other key secondary and composite endpoints, including repeat revascularization, also were not different between the two study groups,” Dr. Jones said.

Regarding safety endpoints, the rates of major bleeding, fatal bleeding, intracranial bleeding, and minor bleeding all were similar between the two study groups.

“These findings suggest that patients with prior revascularization have a substantial residual rate of cardiovascular and acute limb events, despite high adherence to antiplatelet and statin medications, and require further study,” Dr. Jones noted.

*Correction 11/14/16: An earlier version of this article misstated the name of the investigator who presented the study at the meeting.

WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.

The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.

[email protected]

WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.

The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.

[email protected]

WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.

The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.

[email protected]

BOSTON – Direct-acting antiviral therapy does not appear to increase the risk of de novo hepatocellular carcinoma in cirrhotic patients with hepatitis C virus (HCV) infection, according to findings from a prospective cohort study of more than 2,000 patients.

But curing HCV also did not protect patients from hepatocellular carcinoma (HCC), at least during the first 6-12 months after starting treatment, Antonietta Romano, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Clinicians should continue monitoring HCV patients with advanced liver disease, even after they have achieved sustained viral response, she said.

Recent studies had raised concerns about whether direct-acting antivirals (DAA) increase the risk of HCC, said Dr. Romano of the University of Padova (Italy). To clarify the issue, she and her coinvestigators followed 2,279 HCV patients who received approved DAA regimens. Over a median follow-up time of 305 days, 41 patients developed de novo hepatocellular carcinoma, for an incidence of 1.64 cases per 100 patient-years, Dr. Romano said.

“These results indicate that in cirrhotic patients, the incidence of HCC during the first 6-9 months after initiation of direct-acting antiviral therapy is not different from what we expect in untreated patients, according to historical controls,” she added.

Fully 86% of patients had cirrhosis, of which 91% were Child-Pugh A and 9% were Child-Pugh B, indicating more advanced liver disease, Dr. Romano said. Noncirrhotic patients had an HCC rate of 0.23 cases per 100 patient years – less than one-eighth that for cirrhotic patients (1.93 cases per 100 patient-years). Child-Pugh B patients developed 2.9 cases of HCC per 100 patient years, versus 1.6 for Child-Pugh A patients.

These rates resemble those in historical controls, suggesting that stage of liver disease is the crucial predictor of HCC risk – not DAA therapy, Dr. Romano said. Multivariable analyses supported that conclusion, linking HCC to elevated liver enzymes and to thrombocytopenia but not to DAA regimen, gender, age, or HCV genotype, she reported.

Most HCC cases were diagnosed at least 12 weeks after starting therapy, according to Dr. Romano. Half of patients had a single nodular tumor with a typical vascular pattern, but the other half had a more aggressive multifocal infiltrative pattern. The reason for the high proportion of atypical aggressive pattern was unclear, Dr. Romano said. However, DAA therapy causes HCV to abruptly stop replicating in the liver, leading to marked molecular and immunologic changes that might initially cause microscopic tumors to grow faster than before. So while DAA therapy does not increase the overall risk of HCC, it clearly is not protective, she said.

Nearly 70% of patients in this study were male. About 60% had HCV-1 infection, 22% had HCV-2, 19% had HCV-3, and 8% had HCV-4, Dr. Romano said. In all, 28 of 41 patients who developed HCC had achieved sustained virologic response at 12 weeks, while the other 13 had relapsed.

The investigators received no outside funding for this study. Dr. Romano reported ties to Gilead, Abbvie, and Bristol Myers Squibb.

BOSTON – Direct-acting antiviral therapy does not appear to increase the risk of de novo hepatocellular carcinoma in cirrhotic patients with hepatitis C virus (HCV) infection, according to findings from a prospective cohort study of more than 2,000 patients.

But curing HCV also did not protect patients from hepatocellular carcinoma (HCC), at least during the first 6-12 months after starting treatment, Antonietta Romano, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Clinicians should continue monitoring HCV patients with advanced liver disease, even after they have achieved sustained viral response, she said.

Recent studies had raised concerns about whether direct-acting antivirals (DAA) increase the risk of HCC, said Dr. Romano of the University of Padova (Italy). To clarify the issue, she and her coinvestigators followed 2,279 HCV patients who received approved DAA regimens. Over a median follow-up time of 305 days, 41 patients developed de novo hepatocellular carcinoma, for an incidence of 1.64 cases per 100 patient-years, Dr. Romano said.

“These results indicate that in cirrhotic patients, the incidence of HCC during the first 6-9 months after initiation of direct-acting antiviral therapy is not different from what we expect in untreated patients, according to historical controls,” she added.

Fully 86% of patients had cirrhosis, of which 91% were Child-Pugh A and 9% were Child-Pugh B, indicating more advanced liver disease, Dr. Romano said. Noncirrhotic patients had an HCC rate of 0.23 cases per 100 patient years – less than one-eighth that for cirrhotic patients (1.93 cases per 100 patient-years). Child-Pugh B patients developed 2.9 cases of HCC per 100 patient years, versus 1.6 for Child-Pugh A patients.

These rates resemble those in historical controls, suggesting that stage of liver disease is the crucial predictor of HCC risk – not DAA therapy, Dr. Romano said. Multivariable analyses supported that conclusion, linking HCC to elevated liver enzymes and to thrombocytopenia but not to DAA regimen, gender, age, or HCV genotype, she reported.

Most HCC cases were diagnosed at least 12 weeks after starting therapy, according to Dr. Romano. Half of patients had a single nodular tumor with a typical vascular pattern, but the other half had a more aggressive multifocal infiltrative pattern. The reason for the high proportion of atypical aggressive pattern was unclear, Dr. Romano said. However, DAA therapy causes HCV to abruptly stop replicating in the liver, leading to marked molecular and immunologic changes that might initially cause microscopic tumors to grow faster than before. So while DAA therapy does not increase the overall risk of HCC, it clearly is not protective, she said.

Nearly 70% of patients in this study were male. About 60% had HCV-1 infection, 22% had HCV-2, 19% had HCV-3, and 8% had HCV-4, Dr. Romano said. In all, 28 of 41 patients who developed HCC had achieved sustained virologic response at 12 weeks, while the other 13 had relapsed.

The investigators received no outside funding for this study. Dr. Romano reported ties to Gilead, Abbvie, and Bristol Myers Squibb.

BOSTON – Direct-acting antiviral therapy does not appear to increase the risk of de novo hepatocellular carcinoma in cirrhotic patients with hepatitis C virus (HCV) infection, according to findings from a prospective cohort study of more than 2,000 patients.

But curing HCV also did not protect patients from hepatocellular carcinoma (HCC), at least during the first 6-12 months after starting treatment, Antonietta Romano, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Clinicians should continue monitoring HCV patients with advanced liver disease, even after they have achieved sustained viral response, she said.

Recent studies had raised concerns about whether direct-acting antivirals (DAA) increase the risk of HCC, said Dr. Romano of the University of Padova (Italy). To clarify the issue, she and her coinvestigators followed 2,279 HCV patients who received approved DAA regimens. Over a median follow-up time of 305 days, 41 patients developed de novo hepatocellular carcinoma, for an incidence of 1.64 cases per 100 patient-years, Dr. Romano said.

“These results indicate that in cirrhotic patients, the incidence of HCC during the first 6-9 months after initiation of direct-acting antiviral therapy is not different from what we expect in untreated patients, according to historical controls,” she added.

Fully 86% of patients had cirrhosis, of which 91% were Child-Pugh A and 9% were Child-Pugh B, indicating more advanced liver disease, Dr. Romano said. Noncirrhotic patients had an HCC rate of 0.23 cases per 100 patient years – less than one-eighth that for cirrhotic patients (1.93 cases per 100 patient-years). Child-Pugh B patients developed 2.9 cases of HCC per 100 patient years, versus 1.6 for Child-Pugh A patients.

These rates resemble those in historical controls, suggesting that stage of liver disease is the crucial predictor of HCC risk – not DAA therapy, Dr. Romano said. Multivariable analyses supported that conclusion, linking HCC to elevated liver enzymes and to thrombocytopenia but not to DAA regimen, gender, age, or HCV genotype, she reported.

Most HCC cases were diagnosed at least 12 weeks after starting therapy, according to Dr. Romano. Half of patients had a single nodular tumor with a typical vascular pattern, but the other half had a more aggressive multifocal infiltrative pattern. The reason for the high proportion of atypical aggressive pattern was unclear, Dr. Romano said. However, DAA therapy causes HCV to abruptly stop replicating in the liver, leading to marked molecular and immunologic changes that might initially cause microscopic tumors to grow faster than before. So while DAA therapy does not increase the overall risk of HCC, it clearly is not protective, she said.

Nearly 70% of patients in this study were male. About 60% had HCV-1 infection, 22% had HCV-2, 19% had HCV-3, and 8% had HCV-4, Dr. Romano said. In all, 28 of 41 patients who developed HCC had achieved sustained virologic response at 12 weeks, while the other 13 had relapsed.

The investigators received no outside funding for this study. Dr. Romano reported ties to Gilead, Abbvie, and Bristol Myers Squibb.

WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.

In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.

Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.

If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.

“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.

“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”

Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.

ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.

The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.

At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.

But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.

The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.

While Dr. Porter was excited about the findings, he eyed them cautiously.

“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”

Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.

Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.

[email protected]On Twitter @alz_gal

WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.

In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.

Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.

If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.

“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.

“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”

Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.

ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.

The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.

At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.

But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.

The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.

While Dr. Porter was excited about the findings, he eyed them cautiously.

“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”

Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.

Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.

[email protected]On Twitter @alz_gal

WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.

In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.

Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.

If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.

“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.

“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”

Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.

ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.

The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.

At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.

But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.

The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.

While Dr. Porter was excited about the findings, he eyed them cautiously.

“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”

Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.

Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.

[email protected]On Twitter @alz_gal

NEW ORLEANS – A proportion of patients treated appropriately with antibiotics for Staphylococcus aureus bacteremia can generate a negative blood culture followed by a positive one, a new clinical entity researchers are calling the “skip phenomenon.”

“This pattern is really in cases where people have known Staph. aureus bacteremia; it seems to clear; they’re on appropriate antibiotic therapy; and despite that, we see that the blood cultures come back positive again several days later,” explained Justin A. Fiala, MD, of Mayo Clinic in Rochester, Minn.

In a video interview, Dr. Fiala outlined the findings of the first study to identify and characterize this phenomenon.

Certain patients with S. aureus bacteremia could be at higher risk for skip phenomenon, for example. The nested case-control study identified these higher-risk patients, a population that might warrant more clinical testing.

Dr. Fiala also discussed associations with patient outcomes, as well as the overall prevalence of skip phenomenon in his research, which included more than 900 patients with S. aureus bacteremia treated at Mayo Clinic.

Dr. Fiala had no relevant financial disclosures.

[email protected]

NEW ORLEANS – A proportion of patients treated appropriately with antibiotics for Staphylococcus aureus bacteremia can generate a negative blood culture followed by a positive one, a new clinical entity researchers are calling the “skip phenomenon.”

“This pattern is really in cases where people have known Staph. aureus bacteremia; it seems to clear; they’re on appropriate antibiotic therapy; and despite that, we see that the blood cultures come back positive again several days later,” explained Justin A. Fiala, MD, of Mayo Clinic in Rochester, Minn.

In a video interview, Dr. Fiala outlined the findings of the first study to identify and characterize this phenomenon.

Certain patients with S. aureus bacteremia could be at higher risk for skip phenomenon, for example. The nested case-control study identified these higher-risk patients, a population that might warrant more clinical testing.

Dr. Fiala also discussed associations with patient outcomes, as well as the overall prevalence of skip phenomenon in his research, which included more than 900 patients with S. aureus bacteremia treated at Mayo Clinic.

Dr. Fiala had no relevant financial disclosures.

[email protected]

NEW ORLEANS – A proportion of patients treated appropriately with antibiotics for Staphylococcus aureus bacteremia can generate a negative blood culture followed by a positive one, a new clinical entity researchers are calling the “skip phenomenon.”

“This pattern is really in cases where people have known Staph. aureus bacteremia; it seems to clear; they’re on appropriate antibiotic therapy; and despite that, we see that the blood cultures come back positive again several days later,” explained Justin A. Fiala, MD, of Mayo Clinic in Rochester, Minn.

In a video interview, Dr. Fiala outlined the findings of the first study to identify and characterize this phenomenon.

Certain patients with S. aureus bacteremia could be at higher risk for skip phenomenon, for example. The nested case-control study identified these higher-risk patients, a population that might warrant more clinical testing.

Dr. Fiala also discussed associations with patient outcomes, as well as the overall prevalence of skip phenomenon in his research, which included more than 900 patients with S. aureus bacteremia treated at Mayo Clinic.

Dr. Fiala had no relevant financial disclosures.

[email protected]

NEW ORLEANS – All of the growth in the obesity epidemic in young American schoolchildren takes place during their summer vacations, Paul T. von Hippel, PhD, reported at Obesity Week 2016.

He presented an analysis from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-2011 which included a nationally representative study population composed of 18,170 U.S. children in 970 schools who were followed with serial weight and height measurements from the start of kindergarten in 2010 through the end of second grade in 2013.

During the summer, the prevalence of both overweight and obesity increased by roughly 1 percentage point per month. In contrast, during the more than 9 months of each school year, the prevalence of overweight didn’t budge, while the prevalence of obesity decreased modestly, by 0.1 percentage points per month.

These data have far-reaching public health implications. The new evidence suggests that the major risk factors for obesity are located outside of schools. That helps explain why many school-based initiatives focused on improving the nutritional content of school lunches and promoting physical activity have had little impact on the pediatric obesity epidemic, said Dr. von Hippel of the University of Texas at Austin.

The data suggest it’s time to explore the potential of reshaping out-of-school behaviors by promoting summer school and summer camp, curbing food advertising directed at children, providing parental nutrition education, and other interventions, he added.

The explanation for the observed increase in body mass index during summer vacation is unclear. It’s known from other studies that children sleep less and engage in more screen time during summer, which may be relevant, according to Dr. von Hippel.

Simultaneous with Dr. von Hippel’s presentation at Obesity 2016, the study was published online in the journal Obesity (2016 Nov 2. doi: 10.1002/oby.21613).

He reported having no financial conflicts of interest regarding the study, which was funded by the Russell Sage Foundation.

[email protected]

NEW ORLEANS – All of the growth in the obesity epidemic in young American schoolchildren takes place during their summer vacations, Paul T. von Hippel, PhD, reported at Obesity Week 2016.

He presented an analysis from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-2011 which included a nationally representative study population composed of 18,170 U.S. children in 970 schools who were followed with serial weight and height measurements from the start of kindergarten in 2010 through the end of second grade in 2013.

During the summer, the prevalence of both overweight and obesity increased by roughly 1 percentage point per month. In contrast, during the more than 9 months of each school year, the prevalence of overweight didn’t budge, while the prevalence of obesity decreased modestly, by 0.1 percentage points per month.

These data have far-reaching public health implications. The new evidence suggests that the major risk factors for obesity are located outside of schools. That helps explain why many school-based initiatives focused on improving the nutritional content of school lunches and promoting physical activity have had little impact on the pediatric obesity epidemic, said Dr. von Hippel of the University of Texas at Austin.

The data suggest it’s time to explore the potential of reshaping out-of-school behaviors by promoting summer school and summer camp, curbing food advertising directed at children, providing parental nutrition education, and other interventions, he added.

The explanation for the observed increase in body mass index during summer vacation is unclear. It’s known from other studies that children sleep less and engage in more screen time during summer, which may be relevant, according to Dr. von Hippel.

Simultaneous with Dr. von Hippel’s presentation at Obesity 2016, the study was published online in the journal Obesity (2016 Nov 2. doi: 10.1002/oby.21613).

He reported having no financial conflicts of interest regarding the study, which was funded by the Russell Sage Foundation.

[email protected]

NEW ORLEANS – All of the growth in the obesity epidemic in young American schoolchildren takes place during their summer vacations, Paul T. von Hippel, PhD, reported at Obesity Week 2016.

He presented an analysis from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-2011 which included a nationally representative study population composed of 18,170 U.S. children in 970 schools who were followed with serial weight and height measurements from the start of kindergarten in 2010 through the end of second grade in 2013.

During the summer, the prevalence of both overweight and obesity increased by roughly 1 percentage point per month. In contrast, during the more than 9 months of each school year, the prevalence of overweight didn’t budge, while the prevalence of obesity decreased modestly, by 0.1 percentage points per month.

These data have far-reaching public health implications. The new evidence suggests that the major risk factors for obesity are located outside of schools. That helps explain why many school-based initiatives focused on improving the nutritional content of school lunches and promoting physical activity have had little impact on the pediatric obesity epidemic, said Dr. von Hippel of the University of Texas at Austin.

The data suggest it’s time to explore the potential of reshaping out-of-school behaviors by promoting summer school and summer camp, curbing food advertising directed at children, providing parental nutrition education, and other interventions, he added.

The explanation for the observed increase in body mass index during summer vacation is unclear. It’s known from other studies that children sleep less and engage in more screen time during summer, which may be relevant, according to Dr. von Hippel.

Simultaneous with Dr. von Hippel’s presentation at Obesity 2016, the study was published online in the journal Obesity (2016 Nov 2. doi: 10.1002/oby.21613).

He reported having no financial conflicts of interest regarding the study, which was funded by the Russell Sage Foundation.

[email protected]

ATLANTA – A multidose regimen of metronidazole was found to have a lower likelihood of treatment failure than a single-dose regimen in treating trichomoniasis in a meta-analysis presented at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

In its 2015 STD treatment guidelines, the CDC recommends that women with HIV infection who receive a diagnosis of Trichomonas vaginalis infection should be treated with metronidazole 500 mg orally twice daily for 7 days, rather than with a 2-g single dose of metronidazole. However, it recommends a 2-g single dose of either metronidazole or tinidazole for other women with trichomoniasis as first-line treatment.

Courtesy CDC

“[Trichomoniasis] is the most prevalent nonviral sexually transmitted infection in the U.S.; there are estimates of anywhere between 3.7 to 7 million [cases]. It eclipses gonorrhea, chlamydia, and syphilis in its prevalence, and there are about 276 million [cases] worldwide,” she said.

While single-dose therapy is inexpensive and has excellent adherence, recurrence has been a problem.

To compare the effectiveness of single- versus multidose treatment strategies, Dr. Kissinger and her coinvestigators searched Embase, Medline, and clinicaltrials.gov for any studies published before Jan. 25, 2016, that were English-language clinical trials evaluating trichomoniasis and metronidazole, and that compared single with multidose treatment regimens. Nearly 500 articles were identified and reviewed, but only six studies were included for analysis based on relevance and quality. Of those, one study included only HIV-positive women.

The primary endpoint was the pooled relative risk (RR) across all included studies of treatment failure in single- and multidose regimens.

Results showed that women who received single-dose metronidazole were 1.87 times more likely to experience treatment failure than those who received multidose therapy (95% confidence interval, 1.23-2.82; P less than .01). When the investigators excluded the one study involving HIV-positive women, the findings were similar, with those on single-dose therapy being 1.80 times more likely than those on a multidose regimen to experience treatment failure (95% CI, 1.07-3.02; P less than .03).

“Limitations [include] that the quality of the studies were not at the same level as we’d be doing in this decade,” Dr. Kissinger said. “There’s a scarcity of studies that evaluate this topic, [and] clinical trial methods have improved substantially since the 1980s, when most of these studies were done.”

Dr. Kissinger did not report information on financial disclosures.

[email protected]

ATLANTA – A multidose regimen of metronidazole was found to have a lower likelihood of treatment failure than a single-dose regimen in treating trichomoniasis in a meta-analysis presented at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

In its 2015 STD treatment guidelines, the CDC recommends that women with HIV infection who receive a diagnosis of Trichomonas vaginalis infection should be treated with metronidazole 500 mg orally twice daily for 7 days, rather than with a 2-g single dose of metronidazole. However, it recommends a 2-g single dose of either metronidazole or tinidazole for other women with trichomoniasis as first-line treatment.

Courtesy CDC

“[Trichomoniasis] is the most prevalent nonviral sexually transmitted infection in the U.S.; there are estimates of anywhere between 3.7 to 7 million [cases]. It eclipses gonorrhea, chlamydia, and syphilis in its prevalence, and there are about 276 million [cases] worldwide,” she said.

While single-dose therapy is inexpensive and has excellent adherence, recurrence has been a problem.

To compare the effectiveness of single- versus multidose treatment strategies, Dr. Kissinger and her coinvestigators searched Embase, Medline, and clinicaltrials.gov for any studies published before Jan. 25, 2016, that were English-language clinical trials evaluating trichomoniasis and metronidazole, and that compared single with multidose treatment regimens. Nearly 500 articles were identified and reviewed, but only six studies were included for analysis based on relevance and quality. Of those, one study included only HIV-positive women.

The primary endpoint was the pooled relative risk (RR) across all included studies of treatment failure in single- and multidose regimens.

Results showed that women who received single-dose metronidazole were 1.87 times more likely to experience treatment failure than those who received multidose therapy (95% confidence interval, 1.23-2.82; P less than .01). When the investigators excluded the one study involving HIV-positive women, the findings were similar, with those on single-dose therapy being 1.80 times more likely than those on a multidose regimen to experience treatment failure (95% CI, 1.07-3.02; P less than .03).

“Limitations [include] that the quality of the studies were not at the same level as we’d be doing in this decade,” Dr. Kissinger said. “There’s a scarcity of studies that evaluate this topic, [and] clinical trial methods have improved substantially since the 1980s, when most of these studies were done.”

Dr. Kissinger did not report information on financial disclosures.

[email protected]

ATLANTA – A multidose regimen of metronidazole was found to have a lower likelihood of treatment failure than a single-dose regimen in treating trichomoniasis in a meta-analysis presented at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

In its 2015 STD treatment guidelines, the CDC recommends that women with HIV infection who receive a diagnosis of Trichomonas vaginalis infection should be treated with metronidazole 500 mg orally twice daily for 7 days, rather than with a 2-g single dose of metronidazole. However, it recommends a 2-g single dose of either metronidazole or tinidazole for other women with trichomoniasis as first-line treatment.

Courtesy CDC

“[Trichomoniasis] is the most prevalent nonviral sexually transmitted infection in the U.S.; there are estimates of anywhere between 3.7 to 7 million [cases]. It eclipses gonorrhea, chlamydia, and syphilis in its prevalence, and there are about 276 million [cases] worldwide,” she said.

While single-dose therapy is inexpensive and has excellent adherence, recurrence has been a problem.

To compare the effectiveness of single- versus multidose treatment strategies, Dr. Kissinger and her coinvestigators searched Embase, Medline, and clinicaltrials.gov for any studies published before Jan. 25, 2016, that were English-language clinical trials evaluating trichomoniasis and metronidazole, and that compared single with multidose treatment regimens. Nearly 500 articles were identified and reviewed, but only six studies were included for analysis based on relevance and quality. Of those, one study included only HIV-positive women.

The primary endpoint was the pooled relative risk (RR) across all included studies of treatment failure in single- and multidose regimens.

Results showed that women who received single-dose metronidazole were 1.87 times more likely to experience treatment failure than those who received multidose therapy (95% confidence interval, 1.23-2.82; P less than .01). When the investigators excluded the one study involving HIV-positive women, the findings were similar, with those on single-dose therapy being 1.80 times more likely than those on a multidose regimen to experience treatment failure (95% CI, 1.07-3.02; P less than .03).

“Limitations [include] that the quality of the studies were not at the same level as we’d be doing in this decade,” Dr. Kissinger said. “There’s a scarcity of studies that evaluate this topic, [and] clinical trial methods have improved substantially since the 1980s, when most of these studies were done.”

Dr. Kissinger did not report information on financial disclosures.

[email protected]

NEW ORLEANS – The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler

NEW ORLEANS – The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler

NEW ORLEANS – The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News

[email protected] On Twitter @mitchelzoler

BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.

The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).

The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.

In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).

Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.

Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.

The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.

This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.

To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.

The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.

The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.

In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.

RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.

Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.

“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.

Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.

The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.

This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.

Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.

The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.

[email protected]

On Twitter @karioakes

BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.

The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).

The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.

In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).

Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.

Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.

The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.

This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.

To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.

The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.

The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.

In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.

RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.

Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.

“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.

Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.

The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.

This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.

Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.

The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.

[email protected]

On Twitter @karioakes

BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.

The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).

The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.

In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).

Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.

Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.

The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.

This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.

To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.

The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.

The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.

In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.

RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.

Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.

“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.

Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.

The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.

This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.

Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.

The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.

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