A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

CHARLOTTE, N.C. – Children and adolescents without a history of headache may develop prolonged headaches after sustaining a concussion, according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.

“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
 

Few studies have examined prolonged pediatric postconcussion headache

The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.

Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.

The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.

Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
 

Healthy behaviors increased after concussion

Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.

Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).

Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.

In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.

After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
 

Long-term outcomes

Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.

The investigators did not report any study funding or disclosures.

[email protected]

SOURCE: Barissi M et al. CNS 2019, Abstract 95.

CHARLOTTE, N.C. – Children and adolescents without a history of headache may develop prolonged headaches after sustaining a concussion, according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.

“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
 

Few studies have examined prolonged pediatric postconcussion headache

The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.

Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.

The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.

Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
 

Healthy behaviors increased after concussion

Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.

Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).

Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.

In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.

After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
 

Long-term outcomes

Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.

The investigators did not report any study funding or disclosures.

[email protected]

SOURCE: Barissi M et al. CNS 2019, Abstract 95.

CHARLOTTE, N.C. – Children and adolescents without a history of headache may develop prolonged headaches after sustaining a concussion, according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.

“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
 

Few studies have examined prolonged pediatric postconcussion headache

The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.

Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.

The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.

Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
 

Healthy behaviors increased after concussion

Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.

Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).

Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.

In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.

After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
 

Long-term outcomes

Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.

The investigators did not report any study funding or disclosures.

[email protected]

SOURCE: Barissi M et al. CNS 2019, Abstract 95.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.