LOS ANGELES – In acute ischemic stroke patients with small perfusion lesions of less than 15 mL, involvement of the corticospinal tract (CST) may help guide the decision whether to treat with alteplase.

Specifically, patients with hypoperfusion in the CST, but without CST infarction, were more likely to have a modified Rankin Scale score (mRS) of 0-2 at 90 days after treatment with alteplase. Patients with no CST involvement, or with a CST infarct, had worse outcomes with treatment.

The better outcomes “might indicate that hypoperfused CST tissue at baseline could be salvaged by timely reperfusion,” said Min Lou, MD, PhD, vice chair of neurology at Zhejiang University, Hangzhou, China, during her presentation of the study at the International Stroke Conference sponsored by the American Heart Association.

Previous studies have left physicians uncertain what to do with patients presenting with mild stroke, especially strokes that are judged to be potentially disabling despite a low National Institutes of Health Stroke Scale (NIHSS) score. These patients have a lower risk of hemorrhagic conversion, estimated at 0%-2%.

A meta-analysis showed that alteplase treatment in patients with a baseline NIHSS score of 0-4 was associated with a 48% increase in the chance of an excellent outcome. But another study showed that, among patients with a perfusion lesion smaller than 15 mL, treatment with alteplase was less likely than no treatment at all to confer an excellent outcome.

“The challenge is to identify what kind of minor stroke patient would benefit from thrombolysis therapy,” said Dr. Lou.

The researchers analyzed data from the International Stroke Perfusion Imaging Registry (INSPIRE) database, selecting 412 patients with an acute perfusion lesion less than 15 mL who had undergone computed tomography perfusion or magnetic resonance perfusion imaging within 4.5 hours of symptom onset, had had the scan repeated at 24 hours, and who were followed up at 90 days.

Among the patients, 248 were treated with alteplase, and 164 were not. The alteplase-treated group had a mean NIHSS score of 5.0, compared with 4.0 in the untreated group (P = .001). CST hypoperfusion was more common in the treated group (32.3% versus 15.9%, P less than .001), as was CST infarction (14.9% versus 5.5%, P = .004) and 24-hour intracerebral hemorrhage (ICH) (9.3% versus 0.6%, P less than .001).

The researchers divided subjects into three groups: no CST lesion (306 patients), CST hypoperfusion with no CST infarct (60), and CST infarct (46). The 24-hour ICH frequency varied between the groups, with the highest frequency in the CST infarct group (15.2%), followed by the CST hypoperfusion with no infarct group (10.0%), and the no CST lesion group (3.6%, P = .002).

At 90 days, higher frequency of an mRS score of 0-1 was only associated with alteplase treatment in the CST hypoperfusion with no infarct group (76.7% versus 47.1%, P = .035).

The reverse was true in the other groups: No treatment was associated with better odds of an mRS score of 0-1 in the group with no CST lesion (87.7% versus 79.8%, P = .067) and particularly in the group with CST infarct (88.9% versus 32.4%, P = .006).

The study is limited by the fact that it is a retrospective analysis, the investigators cautioned.

The National Natural Science Foundation of China funded the study. Dr. Lou reported having no financial disclosures.

LOS ANGELES – In acute ischemic stroke patients with small perfusion lesions of less than 15 mL, involvement of the corticospinal tract (CST) may help guide the decision whether to treat with alteplase.

Specifically, patients with hypoperfusion in the CST, but without CST infarction, were more likely to have a modified Rankin Scale score (mRS) of 0-2 at 90 days after treatment with alteplase. Patients with no CST involvement, or with a CST infarct, had worse outcomes with treatment.

The better outcomes “might indicate that hypoperfused CST tissue at baseline could be salvaged by timely reperfusion,” said Min Lou, MD, PhD, vice chair of neurology at Zhejiang University, Hangzhou, China, during her presentation of the study at the International Stroke Conference sponsored by the American Heart Association.

Previous studies have left physicians uncertain what to do with patients presenting with mild stroke, especially strokes that are judged to be potentially disabling despite a low National Institutes of Health Stroke Scale (NIHSS) score. These patients have a lower risk of hemorrhagic conversion, estimated at 0%-2%.

A meta-analysis showed that alteplase treatment in patients with a baseline NIHSS score of 0-4 was associated with a 48% increase in the chance of an excellent outcome. But another study showed that, among patients with a perfusion lesion smaller than 15 mL, treatment with alteplase was less likely than no treatment at all to confer an excellent outcome.

“The challenge is to identify what kind of minor stroke patient would benefit from thrombolysis therapy,” said Dr. Lou.

The researchers analyzed data from the International Stroke Perfusion Imaging Registry (INSPIRE) database, selecting 412 patients with an acute perfusion lesion less than 15 mL who had undergone computed tomography perfusion or magnetic resonance perfusion imaging within 4.5 hours of symptom onset, had had the scan repeated at 24 hours, and who were followed up at 90 days.

Among the patients, 248 were treated with alteplase, and 164 were not. The alteplase-treated group had a mean NIHSS score of 5.0, compared with 4.0 in the untreated group (P = .001). CST hypoperfusion was more common in the treated group (32.3% versus 15.9%, P less than .001), as was CST infarction (14.9% versus 5.5%, P = .004) and 24-hour intracerebral hemorrhage (ICH) (9.3% versus 0.6%, P less than .001).

The researchers divided subjects into three groups: no CST lesion (306 patients), CST hypoperfusion with no CST infarct (60), and CST infarct (46). The 24-hour ICH frequency varied between the groups, with the highest frequency in the CST infarct group (15.2%), followed by the CST hypoperfusion with no infarct group (10.0%), and the no CST lesion group (3.6%, P = .002).

At 90 days, higher frequency of an mRS score of 0-1 was only associated with alteplase treatment in the CST hypoperfusion with no infarct group (76.7% versus 47.1%, P = .035).

The reverse was true in the other groups: No treatment was associated with better odds of an mRS score of 0-1 in the group with no CST lesion (87.7% versus 79.8%, P = .067) and particularly in the group with CST infarct (88.9% versus 32.4%, P = .006).

The study is limited by the fact that it is a retrospective analysis, the investigators cautioned.

The National Natural Science Foundation of China funded the study. Dr. Lou reported having no financial disclosures.

LOS ANGELES – In acute ischemic stroke patients with small perfusion lesions of less than 15 mL, involvement of the corticospinal tract (CST) may help guide the decision whether to treat with alteplase.

Specifically, patients with hypoperfusion in the CST, but without CST infarction, were more likely to have a modified Rankin Scale score (mRS) of 0-2 at 90 days after treatment with alteplase. Patients with no CST involvement, or with a CST infarct, had worse outcomes with treatment.

The better outcomes “might indicate that hypoperfused CST tissue at baseline could be salvaged by timely reperfusion,” said Min Lou, MD, PhD, vice chair of neurology at Zhejiang University, Hangzhou, China, during her presentation of the study at the International Stroke Conference sponsored by the American Heart Association.

Previous studies have left physicians uncertain what to do with patients presenting with mild stroke, especially strokes that are judged to be potentially disabling despite a low National Institutes of Health Stroke Scale (NIHSS) score. These patients have a lower risk of hemorrhagic conversion, estimated at 0%-2%.

A meta-analysis showed that alteplase treatment in patients with a baseline NIHSS score of 0-4 was associated with a 48% increase in the chance of an excellent outcome. But another study showed that, among patients with a perfusion lesion smaller than 15 mL, treatment with alteplase was less likely than no treatment at all to confer an excellent outcome.

“The challenge is to identify what kind of minor stroke patient would benefit from thrombolysis therapy,” said Dr. Lou.

The researchers analyzed data from the International Stroke Perfusion Imaging Registry (INSPIRE) database, selecting 412 patients with an acute perfusion lesion less than 15 mL who had undergone computed tomography perfusion or magnetic resonance perfusion imaging within 4.5 hours of symptom onset, had had the scan repeated at 24 hours, and who were followed up at 90 days.

Among the patients, 248 were treated with alteplase, and 164 were not. The alteplase-treated group had a mean NIHSS score of 5.0, compared with 4.0 in the untreated group (P = .001). CST hypoperfusion was more common in the treated group (32.3% versus 15.9%, P less than .001), as was CST infarction (14.9% versus 5.5%, P = .004) and 24-hour intracerebral hemorrhage (ICH) (9.3% versus 0.6%, P less than .001).

The researchers divided subjects into three groups: no CST lesion (306 patients), CST hypoperfusion with no CST infarct (60), and CST infarct (46). The 24-hour ICH frequency varied between the groups, with the highest frequency in the CST infarct group (15.2%), followed by the CST hypoperfusion with no infarct group (10.0%), and the no CST lesion group (3.6%, P = .002).

At 90 days, higher frequency of an mRS score of 0-1 was only associated with alteplase treatment in the CST hypoperfusion with no infarct group (76.7% versus 47.1%, P = .035).

The reverse was true in the other groups: No treatment was associated with better odds of an mRS score of 0-1 in the group with no CST lesion (87.7% versus 79.8%, P = .067) and particularly in the group with CST infarct (88.9% versus 32.4%, P = .006).

The study is limited by the fact that it is a retrospective analysis, the investigators cautioned.

The National Natural Science Foundation of China funded the study. Dr. Lou reported having no financial disclosures.

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

[email protected]

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

[email protected]

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

[email protected]

SAN DIEGO – The apolipoprotein E e4 allele is well known for its association with amyloid deposition in Alzheimer’s disease, but now it also appears to help drive the other key pathological process in the disease: deposition of hyperphosphorylated tau protein.

That’s according to the authors of a PET neuroimaging study presented at the annual meeting of the American Neurological Association.

The finding suggests a pathophysiologic mechanism for Alzheimer’s disease cases that predominantly affect memory.

[email protected]

SOURCE: La Joie R, et al. Abstract M183, American Neurological Association 2017 annual meeting.

SAN DIEGO – The apolipoprotein E e4 allele is well known for its association with amyloid deposition in Alzheimer’s disease, but now it also appears to help drive the other key pathological process in the disease: deposition of hyperphosphorylated tau protein.

That’s according to the authors of a PET neuroimaging study presented at the annual meeting of the American Neurological Association.

The finding suggests a pathophysiologic mechanism for Alzheimer’s disease cases that predominantly affect memory.

[email protected]

SOURCE: La Joie R, et al. Abstract M183, American Neurological Association 2017 annual meeting.

SAN DIEGO – The apolipoprotein E e4 allele is well known for its association with amyloid deposition in Alzheimer’s disease, but now it also appears to help drive the other key pathological process in the disease: deposition of hyperphosphorylated tau protein.

That’s according to the authors of a PET neuroimaging study presented at the annual meeting of the American Neurological Association.

The finding suggests a pathophysiologic mechanism for Alzheimer’s disease cases that predominantly affect memory.

[email protected]

SOURCE: La Joie R, et al. Abstract M183, American Neurological Association 2017 annual meeting.

The Food and Drug Administration has approved an additional indication for plecanatide (Trulance) as a 3-mg, once-daily treatment for irritable bowel syndrome with constipation (IBS-C).

Plecanatide had previously been approved to treat adults with chronic idiopathic constipation (CIC).

[email protected]

The Food and Drug Administration has approved an additional indication for plecanatide (Trulance) as a 3-mg, once-daily treatment for irritable bowel syndrome with constipation (IBS-C).

Plecanatide had previously been approved to treat adults with chronic idiopathic constipation (CIC).

[email protected]

The Food and Drug Administration has approved an additional indication for plecanatide (Trulance) as a 3-mg, once-daily treatment for irritable bowel syndrome with constipation (IBS-C).

Plecanatide had previously been approved to treat adults with chronic idiopathic constipation (CIC).

[email protected]

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

LAS VEGAS – Delayed creation of an ileal pouch anal anastomosis in patients with ulcerative colitis (UC) was associated with a lower risk of postoperative events, compared with creating the pouch at the time of initial surgery, results from an analysis of national data demonstrated.

“More than 600,000 Americans have UC, and 20%-30% of them require surgical management,” Bharati Kochar, MD, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “The surgical procedure of choice for many UC patients is total proctocolectomy with ileal pouch anal anastomosis creation.”

According to Dr. Kochar, an advanced fellow in inflammatory bowel diseases at the University of North Carolina at Chapel Hill, existing American medical literature regarding ileal pouch anal anastomosis (IPAA) comes mostly from quaternary care centers and compares one-stage procedures with multistage procedures.

“The risks between two- to three-stage procedures are not described, and there are no prospective national reports of postoperative adverse events after IPAA creation,” she said.

Using data from the National Surgical Quality Improvement Program, Dr. Kochar and her associates conducted an observational cohort analysis of 2,390 adult patients with a postoperative diagnosis of UC who underwent IPAA procedures between 2011 and 2015. Their aims were to evaluate adverse events within 30 days after an IPAA creation and to compare adverse events between pouch creation at the time of colectomy and delayed pouch creation.

They also performed a subanalysis of total abdominal colectomy with ileostomy (TAC), the first stage in the delayed pouch procedures, versus pouch creation at the time of colectomy. Multivariable modified Poisson regression models were used to estimate risk ratios adjusted for age, sex, race, body mass index, smoking status, diabetes, preoperative albumin, and American Society of Anesthesiologists class.

Of the 2,390 patients, 1,571 had pouches created at the time of colectomy (group A), and 819 had delayed pouch creation (group B).

Compared with patients in group B, those in group A were older (a median age of 40 years vs. 37 years, respectively; P less than .01), were more likely to be on an immunosuppressant (51% vs. 15%; P less than .01), have a lower median preoperative albumin level (3.9 vs. 4.2; P less than .01), and a longer median length of stay (6 days vs. 5 days; P less than .01).

On unadjusted analyses, the researchers also observed that, at 30 days, patients in group A had significantly more major complications, such as mortality and cardiac arrest (12.4% vs. 8.7%; P less than .01); minor complications, such as superficial surgical site infections and pneumonia (11.8% vs. 6.1%; P less than .01); unplanned readmissions (statistically similar at 23.3% vs. 21.3%), and unplanned reoperations (7.7% vs. 3.8%; P less than .01).

After controlling for confounders, patients in group B were significantly less likely to have major complications (relative risk, 0.72), minor complications (RR, 0.48), unplanned readmissions (RR, 0.95), and unplanned reoperations (RR, 0.42).

In the subgroup analysis, Dr. Kochar and her associates observed that patients who underwent TAC were significantly older, compared with patients in group A (a median of 46 years vs. 40 years, respectively; P less than .01), and a higher proportion were on immunosuppressants (69% vs. 51%; P less than .01). “Despite these factors, the risk of adverse events after TAC was lower,” Dr. Kochar said.

She acknowledged certain limitations of the study, including the inability to accurately determine the risk of linked surgeries together and the inability to assess institution and operator factors. Also, data were not collected for the purposes of studying inflammatory bowel disease.

“This is the first prospective assessment of morbidity following IPAA creation in UC patients from a national database,” Dr. Kochar concluded. “Delayed pouch procedures are associated with a lower risk of unplanned reoperations and major and minor complications. Immunosuppression at the time of pouch creation may result in an increased risk of adverse events postoperatively. The findings can be valuable for preoperative risk assessment and postoperative management.”

Dr. Kochar reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Kochar et al. Crohn’s & Colitis Congress 2018 Clinical Abstract 11.

LAS VEGAS – Delayed creation of an ileal pouch anal anastomosis in patients with ulcerative colitis (UC) was associated with a lower risk of postoperative events, compared with creating the pouch at the time of initial surgery, results from an analysis of national data demonstrated.

“More than 600,000 Americans have UC, and 20%-30% of them require surgical management,” Bharati Kochar, MD, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “The surgical procedure of choice for many UC patients is total proctocolectomy with ileal pouch anal anastomosis creation.”

According to Dr. Kochar, an advanced fellow in inflammatory bowel diseases at the University of North Carolina at Chapel Hill, existing American medical literature regarding ileal pouch anal anastomosis (IPAA) comes mostly from quaternary care centers and compares one-stage procedures with multistage procedures.

“The risks between two- to three-stage procedures are not described, and there are no prospective national reports of postoperative adverse events after IPAA creation,” she said.

Using data from the National Surgical Quality Improvement Program, Dr. Kochar and her associates conducted an observational cohort analysis of 2,390 adult patients with a postoperative diagnosis of UC who underwent IPAA procedures between 2011 and 2015. Their aims were to evaluate adverse events within 30 days after an IPAA creation and to compare adverse events between pouch creation at the time of colectomy and delayed pouch creation.

They also performed a subanalysis of total abdominal colectomy with ileostomy (TAC), the first stage in the delayed pouch procedures, versus pouch creation at the time of colectomy. Multivariable modified Poisson regression models were used to estimate risk ratios adjusted for age, sex, race, body mass index, smoking status, diabetes, preoperative albumin, and American Society of Anesthesiologists class.

Of the 2,390 patients, 1,571 had pouches created at the time of colectomy (group A), and 819 had delayed pouch creation (group B).

Compared with patients in group B, those in group A were older (a median age of 40 years vs. 37 years, respectively; P less than .01), were more likely to be on an immunosuppressant (51% vs. 15%; P less than .01), have a lower median preoperative albumin level (3.9 vs. 4.2; P less than .01), and a longer median length of stay (6 days vs. 5 days; P less than .01).

On unadjusted analyses, the researchers also observed that, at 30 days, patients in group A had significantly more major complications, such as mortality and cardiac arrest (12.4% vs. 8.7%; P less than .01); minor complications, such as superficial surgical site infections and pneumonia (11.8% vs. 6.1%; P less than .01); unplanned readmissions (statistically similar at 23.3% vs. 21.3%), and unplanned reoperations (7.7% vs. 3.8%; P less than .01).

After controlling for confounders, patients in group B were significantly less likely to have major complications (relative risk, 0.72), minor complications (RR, 0.48), unplanned readmissions (RR, 0.95), and unplanned reoperations (RR, 0.42).

In the subgroup analysis, Dr. Kochar and her associates observed that patients who underwent TAC were significantly older, compared with patients in group A (a median of 46 years vs. 40 years, respectively; P less than .01), and a higher proportion were on immunosuppressants (69% vs. 51%; P less than .01). “Despite these factors, the risk of adverse events after TAC was lower,” Dr. Kochar said.

She acknowledged certain limitations of the study, including the inability to accurately determine the risk of linked surgeries together and the inability to assess institution and operator factors. Also, data were not collected for the purposes of studying inflammatory bowel disease.

“This is the first prospective assessment of morbidity following IPAA creation in UC patients from a national database,” Dr. Kochar concluded. “Delayed pouch procedures are associated with a lower risk of unplanned reoperations and major and minor complications. Immunosuppression at the time of pouch creation may result in an increased risk of adverse events postoperatively. The findings can be valuable for preoperative risk assessment and postoperative management.”

Dr. Kochar reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Kochar et al. Crohn’s & Colitis Congress 2018 Clinical Abstract 11.

LAS VEGAS – Delayed creation of an ileal pouch anal anastomosis in patients with ulcerative colitis (UC) was associated with a lower risk of postoperative events, compared with creating the pouch at the time of initial surgery, results from an analysis of national data demonstrated.

“More than 600,000 Americans have UC, and 20%-30% of them require surgical management,” Bharati Kochar, MD, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “The surgical procedure of choice for many UC patients is total proctocolectomy with ileal pouch anal anastomosis creation.”

According to Dr. Kochar, an advanced fellow in inflammatory bowel diseases at the University of North Carolina at Chapel Hill, existing American medical literature regarding ileal pouch anal anastomosis (IPAA) comes mostly from quaternary care centers and compares one-stage procedures with multistage procedures.

“The risks between two- to three-stage procedures are not described, and there are no prospective national reports of postoperative adverse events after IPAA creation,” she said.

Using data from the National Surgical Quality Improvement Program, Dr. Kochar and her associates conducted an observational cohort analysis of 2,390 adult patients with a postoperative diagnosis of UC who underwent IPAA procedures between 2011 and 2015. Their aims were to evaluate adverse events within 30 days after an IPAA creation and to compare adverse events between pouch creation at the time of colectomy and delayed pouch creation.

They also performed a subanalysis of total abdominal colectomy with ileostomy (TAC), the first stage in the delayed pouch procedures, versus pouch creation at the time of colectomy. Multivariable modified Poisson regression models were used to estimate risk ratios adjusted for age, sex, race, body mass index, smoking status, diabetes, preoperative albumin, and American Society of Anesthesiologists class.

Of the 2,390 patients, 1,571 had pouches created at the time of colectomy (group A), and 819 had delayed pouch creation (group B).

Compared with patients in group B, those in group A were older (a median age of 40 years vs. 37 years, respectively; P less than .01), were more likely to be on an immunosuppressant (51% vs. 15%; P less than .01), have a lower median preoperative albumin level (3.9 vs. 4.2; P less than .01), and a longer median length of stay (6 days vs. 5 days; P less than .01).

On unadjusted analyses, the researchers also observed that, at 30 days, patients in group A had significantly more major complications, such as mortality and cardiac arrest (12.4% vs. 8.7%; P less than .01); minor complications, such as superficial surgical site infections and pneumonia (11.8% vs. 6.1%; P less than .01); unplanned readmissions (statistically similar at 23.3% vs. 21.3%), and unplanned reoperations (7.7% vs. 3.8%; P less than .01).

After controlling for confounders, patients in group B were significantly less likely to have major complications (relative risk, 0.72), minor complications (RR, 0.48), unplanned readmissions (RR, 0.95), and unplanned reoperations (RR, 0.42).

In the subgroup analysis, Dr. Kochar and her associates observed that patients who underwent TAC were significantly older, compared with patients in group A (a median of 46 years vs. 40 years, respectively; P less than .01), and a higher proportion were on immunosuppressants (69% vs. 51%; P less than .01). “Despite these factors, the risk of adverse events after TAC was lower,” Dr. Kochar said.

She acknowledged certain limitations of the study, including the inability to accurately determine the risk of linked surgeries together and the inability to assess institution and operator factors. Also, data were not collected for the purposes of studying inflammatory bowel disease.

“This is the first prospective assessment of morbidity following IPAA creation in UC patients from a national database,” Dr. Kochar concluded. “Delayed pouch procedures are associated with a lower risk of unplanned reoperations and major and minor complications. Immunosuppression at the time of pouch creation may result in an increased risk of adverse events postoperatively. The findings can be valuable for preoperative risk assessment and postoperative management.”

Dr. Kochar reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Kochar et al. Crohn’s & Colitis Congress 2018 Clinical Abstract 11.

Treating urgency urinary incontinence in women may have the added benefit of improving their quality of sleep, according to a paper published online Jan. 9 in Obstetrics & Gynecology.

Researchers analyzed data from a multicenter, double-blind, randomized, controlled trial of daily antimuscarinic therapy (4-8 mg fesoterodine) or placebo in 645 women with urgency-predominant incontinence, which also evaluated sleep quality and daytime sleepiness.

Silvia Jansen/iStockphoto

SOURCE: Warsi Q et al. Obstet Gynecol. 2018 Feb;131(2):204-11.

Treating urgency urinary incontinence in women may have the added benefit of improving their quality of sleep, according to a paper published online Jan. 9 in Obstetrics & Gynecology.

Researchers analyzed data from a multicenter, double-blind, randomized, controlled trial of daily antimuscarinic therapy (4-8 mg fesoterodine) or placebo in 645 women with urgency-predominant incontinence, which also evaluated sleep quality and daytime sleepiness.

Silvia Jansen/iStockphoto

SOURCE: Warsi Q et al. Obstet Gynecol. 2018 Feb;131(2):204-11.

Treating urgency urinary incontinence in women may have the added benefit of improving their quality of sleep, according to a paper published online Jan. 9 in Obstetrics & Gynecology.

Researchers analyzed data from a multicenter, double-blind, randomized, controlled trial of daily antimuscarinic therapy (4-8 mg fesoterodine) or placebo in 645 women with urgency-predominant incontinence, which also evaluated sleep quality and daytime sleepiness.

Silvia Jansen/iStockphoto

SOURCE: Warsi Q et al. Obstet Gynecol. 2018 Feb;131(2):204-11.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

The recommendation is for emicizumab to be used as routine prophylaxis in patients of all ages who have hemophilia A with factor VIII inhibitors.

The marketing authorization application for emicizumab is being reviewed under accelerated assessment, a procedure granted to medicines the CHMP believes are of major interest for public health and therapeutic innovation.

The CHMP’s opinion on emicizumab will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for emicizumab is based on results from 2 phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting.

HAVEN 1

The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with FVIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

The recommendation is for emicizumab to be used as routine prophylaxis in patients of all ages who have hemophilia A with factor VIII inhibitors.

The marketing authorization application for emicizumab is being reviewed under accelerated assessment, a procedure granted to medicines the CHMP believes are of major interest for public health and therapeutic innovation.

The CHMP’s opinion on emicizumab will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for emicizumab is based on results from 2 phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting.

HAVEN 1

The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with FVIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of emicizumab (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.

The recommendation is for emicizumab to be used as routine prophylaxis in patients of all ages who have hemophilia A with factor VIII inhibitors.

The marketing authorization application for emicizumab is being reviewed under accelerated assessment, a procedure granted to medicines the CHMP believes are of major interest for public health and therapeutic innovation.

The CHMP’s opinion on emicizumab will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation for emicizumab is based on results from 2 phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting.

HAVEN 1

The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with bypassing agents (BPAs) on-demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with FVIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds and 0 treated joint bleeds. None of the patients had treated target joint bleeds.

Forty patients had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

LOS ANGELES – Clot removal in acute ischemic stroke patients using an aspiration catheter was noninferior to clot removal using the standard method, a stent retriever, in a multicenter, randomized trial with 270 patients.

“There is now level I evidence that stent retrievers and primary aspiration have equivalent outcomes in emergent large vessel occlusions,” J Mocco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

The results “will give physicians more choice,” Dr. Mocco said in a video interview. Until now, “many physicians felt that they had to use stent retrievers” because these devices had an much bigger evidence base of efficacy and safety. The new findings provide evidence that supports aspiration as an alternative strategy, said Dr. Mocco, professor of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Medical Center in New York.

The results Dr. Mocco reported from the COMPASS trial (Comparison of Direct Aspiration vs. Stent Retriever as a First Approach) were the second time that clot aspiration was shown to produce outcomes similar to stent retrieval. Similar findings came from a French multicenter trial, ASTER, reported in 2017 (JAMA. 2017 Aug 1;318[5]:443-52).

The study ran at 15 U.S. centers during 2015-2017 and randomized patients with emergent large vessel occlusion strokes to receive initial treatment with either an aspiration catheter or a stent retriever. The specific type of catheter or stent used was left up to each operator. In 83% of the aspiration cases and 81% of the stent retriever cases, the initial device used produced a moderately high or better level of restored blood flow within the occluded artery, with thrombolysis in cerebral infarction (TICI) 2b flow or greater.

The study’s primary efficacy endpoint was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after treatment, which occurred in 52% of patients treated with aspiration first and in 49% of those treated by retrieval first, which met the study’s prespecified criterion for noninferiority of the aspiration strategy, Dr. Mocco reported.

The results also showed suggestions of faster responses in the patients treated by aspiration first, although these did not reach statistical significance. The highest rate of restored blood flow within the occluded artery, TICI 3 flow, occurred in 34% of patients treated by aspiration first and in 23% of those treated with retrieval first. The average time to produce TICI 2b flow or greater was 22 minutes in the aspiration-first patients, compared with 33 minutes among retrieval-first patients.

“I prefer to start with aspiration first because it’s fast and efficient,” Dr. Mocco said. “I find encouragement in the nonsignificant faster rate of reperfusion” seen in the results.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Mocco J et al. ISC 2018, Abstract LB4.

LOS ANGELES – Clot removal in acute ischemic stroke patients using an aspiration catheter was noninferior to clot removal using the standard method, a stent retriever, in a multicenter, randomized trial with 270 patients.

“There is now level I evidence that stent retrievers and primary aspiration have equivalent outcomes in emergent large vessel occlusions,” J Mocco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

The results “will give physicians more choice,” Dr. Mocco said in a video interview. Until now, “many physicians felt that they had to use stent retrievers” because these devices had an much bigger evidence base of efficacy and safety. The new findings provide evidence that supports aspiration as an alternative strategy, said Dr. Mocco, professor of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Medical Center in New York.

The results Dr. Mocco reported from the COMPASS trial (Comparison of Direct Aspiration vs. Stent Retriever as a First Approach) were the second time that clot aspiration was shown to produce outcomes similar to stent retrieval. Similar findings came from a French multicenter trial, ASTER, reported in 2017 (JAMA. 2017 Aug 1;318[5]:443-52).

The study ran at 15 U.S. centers during 2015-2017 and randomized patients with emergent large vessel occlusion strokes to receive initial treatment with either an aspiration catheter or a stent retriever. The specific type of catheter or stent used was left up to each operator. In 83% of the aspiration cases and 81% of the stent retriever cases, the initial device used produced a moderately high or better level of restored blood flow within the occluded artery, with thrombolysis in cerebral infarction (TICI) 2b flow or greater.

The study’s primary efficacy endpoint was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after treatment, which occurred in 52% of patients treated with aspiration first and in 49% of those treated by retrieval first, which met the study’s prespecified criterion for noninferiority of the aspiration strategy, Dr. Mocco reported.

The results also showed suggestions of faster responses in the patients treated by aspiration first, although these did not reach statistical significance. The highest rate of restored blood flow within the occluded artery, TICI 3 flow, occurred in 34% of patients treated by aspiration first and in 23% of those treated with retrieval first. The average time to produce TICI 2b flow or greater was 22 minutes in the aspiration-first patients, compared with 33 minutes among retrieval-first patients.

“I prefer to start with aspiration first because it’s fast and efficient,” Dr. Mocco said. “I find encouragement in the nonsignificant faster rate of reperfusion” seen in the results.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Mocco J et al. ISC 2018, Abstract LB4.

LOS ANGELES – Clot removal in acute ischemic stroke patients using an aspiration catheter was noninferior to clot removal using the standard method, a stent retriever, in a multicenter, randomized trial with 270 patients.

“There is now level I evidence that stent retrievers and primary aspiration have equivalent outcomes in emergent large vessel occlusions,” J Mocco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

The results “will give physicians more choice,” Dr. Mocco said in a video interview. Until now, “many physicians felt that they had to use stent retrievers” because these devices had an much bigger evidence base of efficacy and safety. The new findings provide evidence that supports aspiration as an alternative strategy, said Dr. Mocco, professor of neurosurgery and director of the Cerebrovascular Center at Mount Sinai Medical Center in New York.

The results Dr. Mocco reported from the COMPASS trial (Comparison of Direct Aspiration vs. Stent Retriever as a First Approach) were the second time that clot aspiration was shown to produce outcomes similar to stent retrieval. Similar findings came from a French multicenter trial, ASTER, reported in 2017 (JAMA. 2017 Aug 1;318[5]:443-52).

The study ran at 15 U.S. centers during 2015-2017 and randomized patients with emergent large vessel occlusion strokes to receive initial treatment with either an aspiration catheter or a stent retriever. The specific type of catheter or stent used was left up to each operator. In 83% of the aspiration cases and 81% of the stent retriever cases, the initial device used produced a moderately high or better level of restored blood flow within the occluded artery, with thrombolysis in cerebral infarction (TICI) 2b flow or greater.

The study’s primary efficacy endpoint was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after treatment, which occurred in 52% of patients treated with aspiration first and in 49% of those treated by retrieval first, which met the study’s prespecified criterion for noninferiority of the aspiration strategy, Dr. Mocco reported.

The results also showed suggestions of faster responses in the patients treated by aspiration first, although these did not reach statistical significance. The highest rate of restored blood flow within the occluded artery, TICI 3 flow, occurred in 34% of patients treated by aspiration first and in 23% of those treated with retrieval first. The average time to produce TICI 2b flow or greater was 22 minutes in the aspiration-first patients, compared with 33 minutes among retrieval-first patients.

“I prefer to start with aspiration first because it’s fast and efficient,” Dr. Mocco said. “I find encouragement in the nonsignificant faster rate of reperfusion” seen in the results.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Mocco J et al. ISC 2018, Abstract LB4.

SAN FRANCISCO – Combined therapy using an experimental programmed cell death protein 1 (PD-1) inhibitor and experimental poly ADP-ribose polymerase (PARP) 1/2 inhibitor was generally well tolerated and showed efficacy in a phase 1 study of patients with advanced solid tumors.

Tislelizumab, the anti–PD-1 agent in development for solid and hematologic malignancies, is a humanized IgG4 monoclonal antibody engineered to have minimal Fc-gamma receptor binding. Pamiparib, the PARP 1/2 inhibitor, is hypothesized to promote neoantigen release that may boost the efficacy of tislelizumab. At the Jan. 4 data cutoff, 2 of 49 patients treated with one of five planned dose levels experienced a complete response, 8 had a confirmed partial response, and 4 had an unconfirmed partial response, Linda Mileshkin, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Thus, the objective response rate was 20%, she said, noting that the clinical benefit rate, which encompasses all those with a response as well as those with durable stable disease after at least 24 weeks, was 39%. The median duration of response was 168.5 days

As of the data cutoff, 11 patients, including all those with a complete or partial response, remained on treatment, and 10 patients remained on treatment beyond 200 days, said Dr. Mileshkin of Peter MacCallum Cancer Centre, Melbourne.

Study participants were 42 women and 7 men, with a mean age of 63 years and measurable disease treated with at least 1 prior line of therapy (median of 4), but with no prior exposure to a PARP inhibitor or PD-1 therapy. Primary tumor sites included ovarian/fallopian tube/peritoneal (34 patients); pancreas, prostate, and breast cancer (3 patients each); and bile duct, bladder, cervix, lung, peripheral nerve sheath, and uterus (1 patient each). For the current dose-finding phase of the study (phase 1a), cohorts of 6-13 patients were treated with either tislelizumab at an intravenous dose of 2 mg/kg every 3 weeks plus either an oral dose of 20, 40, or 60 mg of pamiparib (dose levels 1, 2, and 3, respectively), or with tislelizumab at an intravenous dose of 200 mg every 3 weeks plus pamiparib at an oral dose of 40 or 60 mg twice daily (dose levels 4 and 5, respectively), Dr. Mileshkin said.

Phase 1b will be a disease-specific expansion to evaluate preliminary antitumor activity.

The rationale for combining the two agents was “to prove that we could get some up-regulation of tumor-associated antigens by using a PARP inhibitor that may then allow us to improve the antitumor activity of the checkpoint inhibitor,” she said.

Further, the malignancies in the patients include those likely to harbor DNA damage repair deficiencies, she added.

All patients experienced at least one treatment-emergent adverse event; 21 experienced a serious event, and 23 had immune-related adverse events.

“Despite the number of events, most patients were able to continue therapy,” Dr. Mileshkin said, noting that more discontinuation was associated with the PD-1 therapy than with the PARP inhibitor.

Non–immune-related adverse events related to the PARP inhibitor included mostly grade 1 and 2 nausea, fatigue, and diarrhea. Anemia also occurred and was grade 3 in 12% of patients.

“In terms of the PD-1 therapy, we mostly saw grade 1 or 2 nonimmune adverse events and very few grade 3 and 4 events,” she said.

One or more grade 3 immune-related adverse events occurred in 12 patients, and based on reports from participating centers, there “seemed to be a signal here that we were seeing more hepatic toxicity than we might have expected,” she said, explaining that these included increases in transaminases and hepatitis.

“We ended up with 13 patients who had a hepatic adverse event thought to be related to treatment. The median time to onset was 55 days ... and there were 9 patients in whom these events were grade 3 or 4,” she said.

Ten had grade 2 or higher transaminitis, which was most likely autoimmune in nature.

“All of these patients were treated with corticosteroids, and they all recovered promptly from the event. Subsequently, the protocol was amended to try increase real-time hepatic safety monitoring,” she said, noting that the rate of hepatic events has fallen since these changes were made.

“We need to closely monitor that moving forward to try to understand it better,” she said of the hepatic events.

Dose level 4 (tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 mg twice daily) was determined to be the maximum tolerated dose and is the recommended phase 2 dose, she noted.

“We were pleased to see 10 patients respond, with these responses appearing to be durable with this currently short follow-up period, and we look forward to seeing the results of part B,” she concluded, noting that enrollment of patients into disease-specific cohorts for that next phase is ongoing.

This study is sponsored by BeiGene. Dr. Mileshkin reported receiving payment for travel, accommodations, and/or expenses from BeiGene and Roche.

[email protected]

SOURCE: Friedlander M et al. ASCO-SITC Clinical Immuno-Oncology Symposium 2018, Abstract #48.

SAN FRANCISCO – Combined therapy using an experimental programmed cell death protein 1 (PD-1) inhibitor and experimental poly ADP-ribose polymerase (PARP) 1/2 inhibitor was generally well tolerated and showed efficacy in a phase 1 study of patients with advanced solid tumors.

Tislelizumab, the anti–PD-1 agent in development for solid and hematologic malignancies, is a humanized IgG4 monoclonal antibody engineered to have minimal Fc-gamma receptor binding. Pamiparib, the PARP 1/2 inhibitor, is hypothesized to promote neoantigen release that may boost the efficacy of tislelizumab. At the Jan. 4 data cutoff, 2 of 49 patients treated with one of five planned dose levels experienced a complete response, 8 had a confirmed partial response, and 4 had an unconfirmed partial response, Linda Mileshkin, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Thus, the objective response rate was 20%, she said, noting that the clinical benefit rate, which encompasses all those with a response as well as those with durable stable disease after at least 24 weeks, was 39%. The median duration of response was 168.5 days

As of the data cutoff, 11 patients, including all those with a complete or partial response, remained on treatment, and 10 patients remained on treatment beyond 200 days, said Dr. Mileshkin of Peter MacCallum Cancer Centre, Melbourne.

Study participants were 42 women and 7 men, with a mean age of 63 years and measurable disease treated with at least 1 prior line of therapy (median of 4), but with no prior exposure to a PARP inhibitor or PD-1 therapy. Primary tumor sites included ovarian/fallopian tube/peritoneal (34 patients); pancreas, prostate, and breast cancer (3 patients each); and bile duct, bladder, cervix, lung, peripheral nerve sheath, and uterus (1 patient each). For the current dose-finding phase of the study (phase 1a), cohorts of 6-13 patients were treated with either tislelizumab at an intravenous dose of 2 mg/kg every 3 weeks plus either an oral dose of 20, 40, or 60 mg of pamiparib (dose levels 1, 2, and 3, respectively), or with tislelizumab at an intravenous dose of 200 mg every 3 weeks plus pamiparib at an oral dose of 40 or 60 mg twice daily (dose levels 4 and 5, respectively), Dr. Mileshkin said.

Phase 1b will be a disease-specific expansion to evaluate preliminary antitumor activity.

The rationale for combining the two agents was “to prove that we could get some up-regulation of tumor-associated antigens by using a PARP inhibitor that may then allow us to improve the antitumor activity of the checkpoint inhibitor,” she said.

Further, the malignancies in the patients include those likely to harbor DNA damage repair deficiencies, she added.

All patients experienced at least one treatment-emergent adverse event; 21 experienced a serious event, and 23 had immune-related adverse events.

“Despite the number of events, most patients were able to continue therapy,” Dr. Mileshkin said, noting that more discontinuation was associated with the PD-1 therapy than with the PARP inhibitor.

Non–immune-related adverse events related to the PARP inhibitor included mostly grade 1 and 2 nausea, fatigue, and diarrhea. Anemia also occurred and was grade 3 in 12% of patients.

“In terms of the PD-1 therapy, we mostly saw grade 1 or 2 nonimmune adverse events and very few grade 3 and 4 events,” she said.

One or more grade 3 immune-related adverse events occurred in 12 patients, and based on reports from participating centers, there “seemed to be a signal here that we were seeing more hepatic toxicity than we might have expected,” she said, explaining that these included increases in transaminases and hepatitis.

“We ended up with 13 patients who had a hepatic adverse event thought to be related to treatment. The median time to onset was 55 days ... and there were 9 patients in whom these events were grade 3 or 4,” she said.

Ten had grade 2 or higher transaminitis, which was most likely autoimmune in nature.

“All of these patients were treated with corticosteroids, and they all recovered promptly from the event. Subsequently, the protocol was amended to try increase real-time hepatic safety monitoring,” she said, noting that the rate of hepatic events has fallen since these changes were made.

“We need to closely monitor that moving forward to try to understand it better,” she said of the hepatic events.

Dose level 4 (tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 mg twice daily) was determined to be the maximum tolerated dose and is the recommended phase 2 dose, she noted.

“We were pleased to see 10 patients respond, with these responses appearing to be durable with this currently short follow-up period, and we look forward to seeing the results of part B,” she concluded, noting that enrollment of patients into disease-specific cohorts for that next phase is ongoing.

This study is sponsored by BeiGene. Dr. Mileshkin reported receiving payment for travel, accommodations, and/or expenses from BeiGene and Roche.

[email protected]

SOURCE: Friedlander M et al. ASCO-SITC Clinical Immuno-Oncology Symposium 2018, Abstract #48.

SAN FRANCISCO – Combined therapy using an experimental programmed cell death protein 1 (PD-1) inhibitor and experimental poly ADP-ribose polymerase (PARP) 1/2 inhibitor was generally well tolerated and showed efficacy in a phase 1 study of patients with advanced solid tumors.

Tislelizumab, the anti–PD-1 agent in development for solid and hematologic malignancies, is a humanized IgG4 monoclonal antibody engineered to have minimal Fc-gamma receptor binding. Pamiparib, the PARP 1/2 inhibitor, is hypothesized to promote neoantigen release that may boost the efficacy of tislelizumab. At the Jan. 4 data cutoff, 2 of 49 patients treated with one of five planned dose levels experienced a complete response, 8 had a confirmed partial response, and 4 had an unconfirmed partial response, Linda Mileshkin, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Thus, the objective response rate was 20%, she said, noting that the clinical benefit rate, which encompasses all those with a response as well as those with durable stable disease after at least 24 weeks, was 39%. The median duration of response was 168.5 days

As of the data cutoff, 11 patients, including all those with a complete or partial response, remained on treatment, and 10 patients remained on treatment beyond 200 days, said Dr. Mileshkin of Peter MacCallum Cancer Centre, Melbourne.

Study participants were 42 women and 7 men, with a mean age of 63 years and measurable disease treated with at least 1 prior line of therapy (median of 4), but with no prior exposure to a PARP inhibitor or PD-1 therapy. Primary tumor sites included ovarian/fallopian tube/peritoneal (34 patients); pancreas, prostate, and breast cancer (3 patients each); and bile duct, bladder, cervix, lung, peripheral nerve sheath, and uterus (1 patient each). For the current dose-finding phase of the study (phase 1a), cohorts of 6-13 patients were treated with either tislelizumab at an intravenous dose of 2 mg/kg every 3 weeks plus either an oral dose of 20, 40, or 60 mg of pamiparib (dose levels 1, 2, and 3, respectively), or with tislelizumab at an intravenous dose of 200 mg every 3 weeks plus pamiparib at an oral dose of 40 or 60 mg twice daily (dose levels 4 and 5, respectively), Dr. Mileshkin said.

Phase 1b will be a disease-specific expansion to evaluate preliminary antitumor activity.

The rationale for combining the two agents was “to prove that we could get some up-regulation of tumor-associated antigens by using a PARP inhibitor that may then allow us to improve the antitumor activity of the checkpoint inhibitor,” she said.

Further, the malignancies in the patients include those likely to harbor DNA damage repair deficiencies, she added.

All patients experienced at least one treatment-emergent adverse event; 21 experienced a serious event, and 23 had immune-related adverse events.

“Despite the number of events, most patients were able to continue therapy,” Dr. Mileshkin said, noting that more discontinuation was associated with the PD-1 therapy than with the PARP inhibitor.

Non–immune-related adverse events related to the PARP inhibitor included mostly grade 1 and 2 nausea, fatigue, and diarrhea. Anemia also occurred and was grade 3 in 12% of patients.

“In terms of the PD-1 therapy, we mostly saw grade 1 or 2 nonimmune adverse events and very few grade 3 and 4 events,” she said.

One or more grade 3 immune-related adverse events occurred in 12 patients, and based on reports from participating centers, there “seemed to be a signal here that we were seeing more hepatic toxicity than we might have expected,” she said, explaining that these included increases in transaminases and hepatitis.

“We ended up with 13 patients who had a hepatic adverse event thought to be related to treatment. The median time to onset was 55 days ... and there were 9 patients in whom these events were grade 3 or 4,” she said.

Ten had grade 2 or higher transaminitis, which was most likely autoimmune in nature.

“All of these patients were treated with corticosteroids, and they all recovered promptly from the event. Subsequently, the protocol was amended to try increase real-time hepatic safety monitoring,” she said, noting that the rate of hepatic events has fallen since these changes were made.

“We need to closely monitor that moving forward to try to understand it better,” she said of the hepatic events.

Dose level 4 (tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 mg twice daily) was determined to be the maximum tolerated dose and is the recommended phase 2 dose, she noted.

“We were pleased to see 10 patients respond, with these responses appearing to be durable with this currently short follow-up period, and we look forward to seeing the results of part B,” she concluded, noting that enrollment of patients into disease-specific cohorts for that next phase is ongoing.

This study is sponsored by BeiGene. Dr. Mileshkin reported receiving payment for travel, accommodations, and/or expenses from BeiGene and Roche.

[email protected]

SOURCE: Friedlander M et al. ASCO-SITC Clinical Immuno-Oncology Symposium 2018, Abstract #48.