Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

mzoler@mdedge.com

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

mzoler@mdedge.com

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

mzoler@mdedge.com

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

Repeat revascularization was more frequent after left main percutaneous coronary intervention than after coronary artery bypass surgery, but raised the mortality risk after both procedures in a secondary EXCEL analysis.
 

The 3-year rate of any repeat revascularization was 12.9% after PCI and 7.6% after CABG (hazard ratio, 1.73; 95% confidence interval, 1.28-2.33).

“It’s a real difference and shouldn’t be minimized. About 1 in 20 patients will need an additional repeat revascularization after PCI, compared with surgery,” study author Gregg Stone, MD, Icahn School of Medicine at Mount Sinai in New York, said in an interview. “Surgery is a more durable procedure in that regard, and patients need to be informed of that by heart team discussions.”

That said, Dr. Stone highlighted other differences between the two strategies, including more bleeding and atrial fibrillation after surgery and better early quality of life after PCI. There’s also an early myocardial infarction (MI) benefit with PCI but a late MI benefit with surgery, which “is probably a more important difference between the two, as opposed to the difference in repeat revascularization,” he added.

Although the increased need to perform repeat vascularization after PCI is not unexpected, the analysis of 346 repeat revascularizations in 185 patients provides more details on the timing and prognosis of these procedures in left main disease.

The need for repeat revascularization was independently associated with 3-year all-cause mortality (adjusted HR, 2.05; 95% CI, 1.13-3.70) and cardiovascular mortality (adjusted HR, 4.22; 95% CI, 2.10-8.48) for both PCI and CABG (P for interaction = .85 for both outcomes).

The increase in mortality risk, however, was smaller than that for MI (adjusted HR, 4.03; 95% CI, 2.43-6.67) or stroke (adjusted HR, 16.62; 95% CI, 9.97-27.69).

The risk for death peaked in the 30 days after redo revascularization and then declined during follow-up. Most of the deaths were cardiovascular (74/128).

The incidence of repeat left main PCI was only 17.5%, whereas the left main was the most common site for redo revascularization in the CABG group.

Repeat revascularization of the index target vessel and target lesion – but not of other lesions – were both strongly associated with increased all-cause and cardiovascular mortality, the authors reported January 15 in JACC: Cardiovascular Interventions.

“It just continues to show that, no matter what intervention we use, we haven’t achieved perfection yet and the opportunities for improvement and decision making between a PCI and a CABG is still up in the air,” Richard J. Shemin, MD, chief of cardiac surgery, UCLA Medical Center, Los Angeles, said in an interview. “And there’s some evidence to suggest coronary bypass might be better in terms of mortality and the need for repeat revascularization.”


 

Enhancing durability

“Measures to reduce the need for repeat revascularization including improved stent platforms and implantation technique, use of pan-arterial bypass grafting, and aggressive risk factor control with guideline-directed medical therapy may improve prognosis after both PCI and CABG,” the authors concluded.

In a linked editorial, David O. Williams, MD, and Pinak B. Shah, MD, both with Brigham and Women’s Hospital and Harvard Medical School, Boston, say intravascular imaging should be “mandatory for all complex PCI,” but that intravascular ultrasound was used in only 77.2% of cases in EXCEL.

5-year kerfuffle

As previously reported, the EXCEL trial’s 5-year analysis showed no significant difference between PCI and CABG for the primary endpoint of all-cause death, MI, or stroke.

However, recent allegations that key MI data were withheld have called into question the final conclusion of relative parity and led the European Association for Cardio-Thoracic Surgery (EACTS) to withdraw support for the left main portion of the 2018 EACTS-European Society of Cardiology (ESC) clinical guidelines based on 3-year EXCEL outcomes.

On January 14, the Society of Thoracic Surgeons (STS) joined EACTS and the American Association for Thoracic Surgery in calling for independent reanalysis of the EXCEL data.

“Any final conclusions drawn from the EXCEL trial will not only affect the actions of physicians, surgeons, regulatory agencies, and third-party payers but, more importantly, they will seriously impact the health and wellbeing of our patients and their families for years to come,” the statement says.

“Given such potentially profound consequences, the Society believes that the final interpretation regarding the outcomes of the EXCEL study should wait until an independent analysis of all aspects of the EXCEL study has been performed.”

EXCEL was sponsored by Abbott Vascular. Dr. Stone reported speaker honoraria from Terumo and Amaranth and serving as a consultant to Reva. Coauthor conflict of interest disclosures are listed in the paper. Dr. Shemin reported no relevant conflicts of interest.
 

This article first appeared on Medscape.com.

Repeat revascularization was more frequent after left main percutaneous coronary intervention than after coronary artery bypass surgery, but raised the mortality risk after both procedures in a secondary EXCEL analysis.
 

The 3-year rate of any repeat revascularization was 12.9% after PCI and 7.6% after CABG (hazard ratio, 1.73; 95% confidence interval, 1.28-2.33).

“It’s a real difference and shouldn’t be minimized. About 1 in 20 patients will need an additional repeat revascularization after PCI, compared with surgery,” study author Gregg Stone, MD, Icahn School of Medicine at Mount Sinai in New York, said in an interview. “Surgery is a more durable procedure in that regard, and patients need to be informed of that by heart team discussions.”

That said, Dr. Stone highlighted other differences between the two strategies, including more bleeding and atrial fibrillation after surgery and better early quality of life after PCI. There’s also an early myocardial infarction (MI) benefit with PCI but a late MI benefit with surgery, which “is probably a more important difference between the two, as opposed to the difference in repeat revascularization,” he added.

Although the increased need to perform repeat vascularization after PCI is not unexpected, the analysis of 346 repeat revascularizations in 185 patients provides more details on the timing and prognosis of these procedures in left main disease.

The need for repeat revascularization was independently associated with 3-year all-cause mortality (adjusted HR, 2.05; 95% CI, 1.13-3.70) and cardiovascular mortality (adjusted HR, 4.22; 95% CI, 2.10-8.48) for both PCI and CABG (P for interaction = .85 for both outcomes).

The increase in mortality risk, however, was smaller than that for MI (adjusted HR, 4.03; 95% CI, 2.43-6.67) or stroke (adjusted HR, 16.62; 95% CI, 9.97-27.69).

The risk for death peaked in the 30 days after redo revascularization and then declined during follow-up. Most of the deaths were cardiovascular (74/128).

The incidence of repeat left main PCI was only 17.5%, whereas the left main was the most common site for redo revascularization in the CABG group.

Repeat revascularization of the index target vessel and target lesion – but not of other lesions – were both strongly associated with increased all-cause and cardiovascular mortality, the authors reported January 15 in JACC: Cardiovascular Interventions.

“It just continues to show that, no matter what intervention we use, we haven’t achieved perfection yet and the opportunities for improvement and decision making between a PCI and a CABG is still up in the air,” Richard J. Shemin, MD, chief of cardiac surgery, UCLA Medical Center, Los Angeles, said in an interview. “And there’s some evidence to suggest coronary bypass might be better in terms of mortality and the need for repeat revascularization.”


 

Enhancing durability

“Measures to reduce the need for repeat revascularization including improved stent platforms and implantation technique, use of pan-arterial bypass grafting, and aggressive risk factor control with guideline-directed medical therapy may improve prognosis after both PCI and CABG,” the authors concluded.

In a linked editorial, David O. Williams, MD, and Pinak B. Shah, MD, both with Brigham and Women’s Hospital and Harvard Medical School, Boston, say intravascular imaging should be “mandatory for all complex PCI,” but that intravascular ultrasound was used in only 77.2% of cases in EXCEL.

5-year kerfuffle

As previously reported, the EXCEL trial’s 5-year analysis showed no significant difference between PCI and CABG for the primary endpoint of all-cause death, MI, or stroke.

However, recent allegations that key MI data were withheld have called into question the final conclusion of relative parity and led the European Association for Cardio-Thoracic Surgery (EACTS) to withdraw support for the left main portion of the 2018 EACTS-European Society of Cardiology (ESC) clinical guidelines based on 3-year EXCEL outcomes.

On January 14, the Society of Thoracic Surgeons (STS) joined EACTS and the American Association for Thoracic Surgery in calling for independent reanalysis of the EXCEL data.

“Any final conclusions drawn from the EXCEL trial will not only affect the actions of physicians, surgeons, regulatory agencies, and third-party payers but, more importantly, they will seriously impact the health and wellbeing of our patients and their families for years to come,” the statement says.

“Given such potentially profound consequences, the Society believes that the final interpretation regarding the outcomes of the EXCEL study should wait until an independent analysis of all aspects of the EXCEL study has been performed.”

EXCEL was sponsored by Abbott Vascular. Dr. Stone reported speaker honoraria from Terumo and Amaranth and serving as a consultant to Reva. Coauthor conflict of interest disclosures are listed in the paper. Dr. Shemin reported no relevant conflicts of interest.
 

This article first appeared on Medscape.com.

Repeat revascularization was more frequent after left main percutaneous coronary intervention than after coronary artery bypass surgery, but raised the mortality risk after both procedures in a secondary EXCEL analysis.
 

The 3-year rate of any repeat revascularization was 12.9% after PCI and 7.6% after CABG (hazard ratio, 1.73; 95% confidence interval, 1.28-2.33).

“It’s a real difference and shouldn’t be minimized. About 1 in 20 patients will need an additional repeat revascularization after PCI, compared with surgery,” study author Gregg Stone, MD, Icahn School of Medicine at Mount Sinai in New York, said in an interview. “Surgery is a more durable procedure in that regard, and patients need to be informed of that by heart team discussions.”

That said, Dr. Stone highlighted other differences between the two strategies, including more bleeding and atrial fibrillation after surgery and better early quality of life after PCI. There’s also an early myocardial infarction (MI) benefit with PCI but a late MI benefit with surgery, which “is probably a more important difference between the two, as opposed to the difference in repeat revascularization,” he added.

Although the increased need to perform repeat vascularization after PCI is not unexpected, the analysis of 346 repeat revascularizations in 185 patients provides more details on the timing and prognosis of these procedures in left main disease.

The need for repeat revascularization was independently associated with 3-year all-cause mortality (adjusted HR, 2.05; 95% CI, 1.13-3.70) and cardiovascular mortality (adjusted HR, 4.22; 95% CI, 2.10-8.48) for both PCI and CABG (P for interaction = .85 for both outcomes).

The increase in mortality risk, however, was smaller than that for MI (adjusted HR, 4.03; 95% CI, 2.43-6.67) or stroke (adjusted HR, 16.62; 95% CI, 9.97-27.69).

The risk for death peaked in the 30 days after redo revascularization and then declined during follow-up. Most of the deaths were cardiovascular (74/128).

The incidence of repeat left main PCI was only 17.5%, whereas the left main was the most common site for redo revascularization in the CABG group.

Repeat revascularization of the index target vessel and target lesion – but not of other lesions – were both strongly associated with increased all-cause and cardiovascular mortality, the authors reported January 15 in JACC: Cardiovascular Interventions.

“It just continues to show that, no matter what intervention we use, we haven’t achieved perfection yet and the opportunities for improvement and decision making between a PCI and a CABG is still up in the air,” Richard J. Shemin, MD, chief of cardiac surgery, UCLA Medical Center, Los Angeles, said in an interview. “And there’s some evidence to suggest coronary bypass might be better in terms of mortality and the need for repeat revascularization.”


 

Enhancing durability

“Measures to reduce the need for repeat revascularization including improved stent platforms and implantation technique, use of pan-arterial bypass grafting, and aggressive risk factor control with guideline-directed medical therapy may improve prognosis after both PCI and CABG,” the authors concluded.

In a linked editorial, David O. Williams, MD, and Pinak B. Shah, MD, both with Brigham and Women’s Hospital and Harvard Medical School, Boston, say intravascular imaging should be “mandatory for all complex PCI,” but that intravascular ultrasound was used in only 77.2% of cases in EXCEL.

5-year kerfuffle

As previously reported, the EXCEL trial’s 5-year analysis showed no significant difference between PCI and CABG for the primary endpoint of all-cause death, MI, or stroke.

However, recent allegations that key MI data were withheld have called into question the final conclusion of relative parity and led the European Association for Cardio-Thoracic Surgery (EACTS) to withdraw support for the left main portion of the 2018 EACTS-European Society of Cardiology (ESC) clinical guidelines based on 3-year EXCEL outcomes.

On January 14, the Society of Thoracic Surgeons (STS) joined EACTS and the American Association for Thoracic Surgery in calling for independent reanalysis of the EXCEL data.

“Any final conclusions drawn from the EXCEL trial will not only affect the actions of physicians, surgeons, regulatory agencies, and third-party payers but, more importantly, they will seriously impact the health and wellbeing of our patients and their families for years to come,” the statement says.

“Given such potentially profound consequences, the Society believes that the final interpretation regarding the outcomes of the EXCEL study should wait until an independent analysis of all aspects of the EXCEL study has been performed.”

EXCEL was sponsored by Abbott Vascular. Dr. Stone reported speaker honoraria from Terumo and Amaranth and serving as a consultant to Reva. Coauthor conflict of interest disclosures are listed in the paper. Dr. Shemin reported no relevant conflicts of interest.
 

This article first appeared on Medscape.com.

The prevalence of abdominal aortic aneurysms (AAAs) is decreasing, thought to be caused by a decrease in smoking. But the risk of death if one ruptures is as high as 81%. So, screening is still an important part of preventive medicine.

When the abdominal aorta enlarges to greater than 3.0 cm, it is considered an aneurysm. Risk factors that can lead to an enlarged aorta include older age, male sex, smoking, history of AAA in a first-degree relative, hypertension, history of other aneurysms, coronary artery disease, cerebrovascular disease, atherosclerosis, and hypercholesterolemia.

History of AAA in a first-degree relative puts patients at double the risk of developing an abdominal aortic aneurysm. Interestingly, diabetes has been associated with a reduced risk of AAA. People of African American, Asian, and Hispanic descent have a reduced risk of AAA.
 

Screening

Screening is performed using abdominal duplex ultrasound. It has high sensitivity (94%-100%) and specificity (98%-100%), is low cost, and has low risk to the patient. The U.S. Preventive Services Task Force breaks its screening recommendations into four categories:

1. Men aged 65-75 years who have ever smoked (at least 100 cigarettes in their lifetime): One-time screening (grade B, moderate net benefit).

2. Men aged 65-75 years who have never smoked: Selectively offer screening (grade C, small net benefit). “To determine whether this service is appropriate, patients and clinicians should consider the patient’s medical history, family history, other risk factors, and personal values.”

3. Women without a smoking history or family history of AAA: Do not perform screening (grade D, recommendation against the service).

4. Women aged 65-75 years who have a smoking history or family history of AAA: There is insufficient evidence on whether or not to screen for AAA (grade I, insufficient evidence).

To assess screening and treatment of AAAs, the USPSTF looked at four randomized, controlled trials largely focused on men older than 65 years. With the combined data, they found 246 men would need to be screened to prevent 1 AAA rupture, and 305 men would need to be screened to prevent 1 death from AAA.

The USPSTF does note that, while the risk of death is lower for elective AAA repair than ruptured AAA, there is still increased risk with elective surgery. In addition, increased screening and detection increases the rate of elective surgery. Overdiagnosis and overtreatment could represent a harm.
 

Treatment

Surgical repair of AAA in men depends on the size of the aneurysm and rate of growth.

For men, surgical repair is standard when the AAA reaches 5.5 cm or if the AAA is growing faster than 1.0 cm per year and is larger than 4.0 cm. For women, surgical repair is often recommended between 5.0 cm and 5.4 cm in size.

Surgical repair is not recommended for AAAs that are less than 5.0 cm because the annual risk of rupture is 0%-1% below 5.0 cm. The risk increases to 11% for aneurysms that are 5.0-5.9 cm in size.

There are two methods of surgical repair: endovascular aneurysm repair and open repair. Recommendations for the surveillance of AAA between 3.0 cm and 5.5 cm is regular ultrasound surveillance, with the interval becoming shorter as the aneurysm size becomes larger. Exact intervals differ from one guideline group to another.
 

Screening and treatment in women

While it is true that AAAs in women are more likely to rupture at smaller sizes than AAAs in men, the AAAs that rupture in women are more likely to rupture at an older age than AAAs rupture in men.

The prevalence of AAAs in women is thought to be one-sixth of the prevalence of men. In addition, women had a higher 30-day mortality after surgical repair. They also had higher rates of complications for elective surgical repair of AAAs.

For these reasons, it is unclear that the benefits of AAA screening and treatment in women outweigh the risks, and the USPSTF cannot come to a conclusive recommendation for women who have ever smoked or women who have a family history of AAA.

The USPSTF is able to state definitively that they do not recommend screening in women with no smoking history or family history of AAA.
 

Bottom line

The USPSTF recommends screening men aged 65-75 years who have ever smoked and selectively screening men aged 65-75 years with no smoking history. The USPSTF recommends against screening women aged 65-75 years who have never smoked and have no family history of AAA. There is insufficient evidence to either recommend for or against screening women aged 65-75 years who have smoked or have a family history of AAA.

Reference

Owens DK et al. Screening for abdominal aortic aneurysm: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2019 Dec 10;322(22):2211-18.

Dr. Sprogell is a second-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

The prevalence of abdominal aortic aneurysms (AAAs) is decreasing, thought to be caused by a decrease in smoking. But the risk of death if one ruptures is as high as 81%. So, screening is still an important part of preventive medicine.

When the abdominal aorta enlarges to greater than 3.0 cm, it is considered an aneurysm. Risk factors that can lead to an enlarged aorta include older age, male sex, smoking, history of AAA in a first-degree relative, hypertension, history of other aneurysms, coronary artery disease, cerebrovascular disease, atherosclerosis, and hypercholesterolemia.

History of AAA in a first-degree relative puts patients at double the risk of developing an abdominal aortic aneurysm. Interestingly, diabetes has been associated with a reduced risk of AAA. People of African American, Asian, and Hispanic descent have a reduced risk of AAA.
 

Screening

Screening is performed using abdominal duplex ultrasound. It has high sensitivity (94%-100%) and specificity (98%-100%), is low cost, and has low risk to the patient. The U.S. Preventive Services Task Force breaks its screening recommendations into four categories:

1. Men aged 65-75 years who have ever smoked (at least 100 cigarettes in their lifetime): One-time screening (grade B, moderate net benefit).

2. Men aged 65-75 years who have never smoked: Selectively offer screening (grade C, small net benefit). “To determine whether this service is appropriate, patients and clinicians should consider the patient’s medical history, family history, other risk factors, and personal values.”

3. Women without a smoking history or family history of AAA: Do not perform screening (grade D, recommendation against the service).

4. Women aged 65-75 years who have a smoking history or family history of AAA: There is insufficient evidence on whether or not to screen for AAA (grade I, insufficient evidence).

To assess screening and treatment of AAAs, the USPSTF looked at four randomized, controlled trials largely focused on men older than 65 years. With the combined data, they found 246 men would need to be screened to prevent 1 AAA rupture, and 305 men would need to be screened to prevent 1 death from AAA.

The USPSTF does note that, while the risk of death is lower for elective AAA repair than ruptured AAA, there is still increased risk with elective surgery. In addition, increased screening and detection increases the rate of elective surgery. Overdiagnosis and overtreatment could represent a harm.
 

Treatment

Surgical repair of AAA in men depends on the size of the aneurysm and rate of growth.

For men, surgical repair is standard when the AAA reaches 5.5 cm or if the AAA is growing faster than 1.0 cm per year and is larger than 4.0 cm. For women, surgical repair is often recommended between 5.0 cm and 5.4 cm in size.

Surgical repair is not recommended for AAAs that are less than 5.0 cm because the annual risk of rupture is 0%-1% below 5.0 cm. The risk increases to 11% for aneurysms that are 5.0-5.9 cm in size.

There are two methods of surgical repair: endovascular aneurysm repair and open repair. Recommendations for the surveillance of AAA between 3.0 cm and 5.5 cm is regular ultrasound surveillance, with the interval becoming shorter as the aneurysm size becomes larger. Exact intervals differ from one guideline group to another.
 

Screening and treatment in women

While it is true that AAAs in women are more likely to rupture at smaller sizes than AAAs in men, the AAAs that rupture in women are more likely to rupture at an older age than AAAs rupture in men.

The prevalence of AAAs in women is thought to be one-sixth of the prevalence of men. In addition, women had a higher 30-day mortality after surgical repair. They also had higher rates of complications for elective surgical repair of AAAs.

For these reasons, it is unclear that the benefits of AAA screening and treatment in women outweigh the risks, and the USPSTF cannot come to a conclusive recommendation for women who have ever smoked or women who have a family history of AAA.

The USPSTF is able to state definitively that they do not recommend screening in women with no smoking history or family history of AAA.
 

Bottom line

The USPSTF recommends screening men aged 65-75 years who have ever smoked and selectively screening men aged 65-75 years with no smoking history. The USPSTF recommends against screening women aged 65-75 years who have never smoked and have no family history of AAA. There is insufficient evidence to either recommend for or against screening women aged 65-75 years who have smoked or have a family history of AAA.

Reference

Owens DK et al. Screening for abdominal aortic aneurysm: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2019 Dec 10;322(22):2211-18.

Dr. Sprogell is a second-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

The prevalence of abdominal aortic aneurysms (AAAs) is decreasing, thought to be caused by a decrease in smoking. But the risk of death if one ruptures is as high as 81%. So, screening is still an important part of preventive medicine.

When the abdominal aorta enlarges to greater than 3.0 cm, it is considered an aneurysm. Risk factors that can lead to an enlarged aorta include older age, male sex, smoking, history of AAA in a first-degree relative, hypertension, history of other aneurysms, coronary artery disease, cerebrovascular disease, atherosclerosis, and hypercholesterolemia.

History of AAA in a first-degree relative puts patients at double the risk of developing an abdominal aortic aneurysm. Interestingly, diabetes has been associated with a reduced risk of AAA. People of African American, Asian, and Hispanic descent have a reduced risk of AAA.
 

Screening

Screening is performed using abdominal duplex ultrasound. It has high sensitivity (94%-100%) and specificity (98%-100%), is low cost, and has low risk to the patient. The U.S. Preventive Services Task Force breaks its screening recommendations into four categories:

1. Men aged 65-75 years who have ever smoked (at least 100 cigarettes in their lifetime): One-time screening (grade B, moderate net benefit).

2. Men aged 65-75 years who have never smoked: Selectively offer screening (grade C, small net benefit). “To determine whether this service is appropriate, patients and clinicians should consider the patient’s medical history, family history, other risk factors, and personal values.”

3. Women without a smoking history or family history of AAA: Do not perform screening (grade D, recommendation against the service).

4. Women aged 65-75 years who have a smoking history or family history of AAA: There is insufficient evidence on whether or not to screen for AAA (grade I, insufficient evidence).

To assess screening and treatment of AAAs, the USPSTF looked at four randomized, controlled trials largely focused on men older than 65 years. With the combined data, they found 246 men would need to be screened to prevent 1 AAA rupture, and 305 men would need to be screened to prevent 1 death from AAA.

The USPSTF does note that, while the risk of death is lower for elective AAA repair than ruptured AAA, there is still increased risk with elective surgery. In addition, increased screening and detection increases the rate of elective surgery. Overdiagnosis and overtreatment could represent a harm.
 

Treatment

Surgical repair of AAA in men depends on the size of the aneurysm and rate of growth.

For men, surgical repair is standard when the AAA reaches 5.5 cm or if the AAA is growing faster than 1.0 cm per year and is larger than 4.0 cm. For women, surgical repair is often recommended between 5.0 cm and 5.4 cm in size.

Surgical repair is not recommended for AAAs that are less than 5.0 cm because the annual risk of rupture is 0%-1% below 5.0 cm. The risk increases to 11% for aneurysms that are 5.0-5.9 cm in size.

There are two methods of surgical repair: endovascular aneurysm repair and open repair. Recommendations for the surveillance of AAA between 3.0 cm and 5.5 cm is regular ultrasound surveillance, with the interval becoming shorter as the aneurysm size becomes larger. Exact intervals differ from one guideline group to another.
 

Screening and treatment in women

While it is true that AAAs in women are more likely to rupture at smaller sizes than AAAs in men, the AAAs that rupture in women are more likely to rupture at an older age than AAAs rupture in men.

The prevalence of AAAs in women is thought to be one-sixth of the prevalence of men. In addition, women had a higher 30-day mortality after surgical repair. They also had higher rates of complications for elective surgical repair of AAAs.

For these reasons, it is unclear that the benefits of AAA screening and treatment in women outweigh the risks, and the USPSTF cannot come to a conclusive recommendation for women who have ever smoked or women who have a family history of AAA.

The USPSTF is able to state definitively that they do not recommend screening in women with no smoking history or family history of AAA.
 

Bottom line

The USPSTF recommends screening men aged 65-75 years who have ever smoked and selectively screening men aged 65-75 years with no smoking history. The USPSTF recommends against screening women aged 65-75 years who have never smoked and have no family history of AAA. There is insufficient evidence to either recommend for or against screening women aged 65-75 years who have smoked or have a family history of AAA.

Reference

Owens DK et al. Screening for abdominal aortic aneurysm: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2019 Dec 10;322(22):2211-18.

Dr. Sprogell is a second-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com