ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

ATLANTA – Ixekizumab (Taltz) provided significantly greater improvement in joint and skin symptoms, compared with adalimumab (Humira), in biologic-naive patients with active psoriatic arthritis (PsA), according to final 52-week safety and efficacy results from the randomized SPIRIT-H2H study.

The high-affinity monoclonal antibody against interleukin-17A also performed at least as well as the tumor necrosis factor (TNF)–inhibitor adalimumab across multiple PsA domains and regardless of methotrexate use, Josef Smolen, MD, reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

Multiple biologic disease-modifying antirheumatic drugs (bDMARDs) are available for the treatment of PsA, but few studies have directly compared their efficacy and safety, said Dr. Smolen of the Medical University of Vienna. He noted that the SPIRIT-H2H study aimed to compare ixekizumab and adalimumab and also to address “one of the most clinically relevant questions for clinicians,” which relates to the efficacy of bDMARDs with and without concomitant methotrexate.

Ixekizumab is approved for adults with active PsA and moderate to severe plaque psoriasis, but TNF inhibitors like adalimumab have long been considered the gold standard for PsA treatment, he explained.

Of 283 patients with PsA randomized to receive ixekizumab and 283 randomized to receive adalimumab, 87% and 84%, respectively, completed week 52 of the head-to-head, open-label study comparing the bDMARDs. Treatment with ixekizumab achieved the primary endpoint of simultaneous improvement of 50% on ACR response criteria (ACR50) and 100% on the Psoriasis Area and Severity Index (PASI100) in 39% of patients, which was significantly higher than the rate of 26% with adalimumab, Dr. Smolen said.

Ixekizumab also performed at least as well as adalimumab for the secondary outcome measures of ACR50 response (50% in both groups) and PASI100 response (64% vs. 41%), as well as for all other outcomes measures, including multiple musculoskeletal PsA domains, he said.

“Remarkably ... at 1 year, more than one-third of the patients achieved an ACR70 in both groups, and half of the patients achieved an ACR50,” he added, noting that the ACR100 responses were in line with previous investigations.

Stratification by methotrexate use showed that the simultaneous ACR50 and PASI100 response rates were improved with ixekizumab versus adalimumab both in users and nonusers of methotrexate (39% vs. 30% and 40% vs. 20%, respectively). This finding highlights the ongoing debate about whether TNF inhibitors should or should not be used with methotrexate for PsA.

“This study was not adequately powered to say that, but there is some indication, and I think that this is food for thought for future further analysis because the data in the literature are discrepant in this respect,” Dr. Smolen said.

In non-methotrexate users in SPIRIT-H2H, the ACR20 responses were 53% with ixekinumab vs. 40% with adalimumab, ACR50 responses were 72% vs. 60%, and ACR70 responses were 41% vs. 27%, respectively, he said noting that the difference for ACR70 was statistically significant, and that the ACR70 response with ixekinumab was about the same as the ACR50 for adalimumab.

As for ACR20, ACR50, and ACR70 responses in methotrexate users, “the lines criss-crossed” early on, he said, but all were “slightly superior” with adalimumab than with ixekizumab at 52 weeks (75% vs. 68%, 56% vs. 48%, and 39% vs. 32%, respectively).

Study participants had a mean age of 48 years and had active PsA with at least 3/66 tender joints, at least 3/68 swollen joints, at least 3% psoriasis body surface area involvement, no prior treatment with bDMARDs, and prior inadequate response to one or more conventional synthetic DMARDs. Treatment was dosed according to drug labeling through 52 weeks.

The safety profiles of both agents were consistent with previous reports; treatment-emergent adverse events occurred in 73.9% of ixekizumab and 68.6% of adalimumab patients, and serious adverse events occurred in 4.2% and 12.4%, respectively.

“On the other hand, ixekizumab had more injection site reactions: 11% vs. close to 4%,” he said, noting that 4.2% of the ixekizumab patients and 7.4% of the adalimumab patients discontinued treatment because of adverse events. No deaths occurred in either group.

As reported previously in Annals of the Rheumatic Diseases, ixekizumab was superior to adalimumab for simultaneous achievement of ACR50 and PASI100 at 24 weeks, and these final 52-week results confirm those results, he said.

The study was funded by Eli Lilly, which markets ixekizumab. Dr. Smolen reported research grants and/or honoraria from Eli Lilly and AbbVie, which markets adalimumab, as well as many other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Smolen J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L20.

Women with ADHD, autism spectrum disorder (ASD), or both report higher rates of chronic pain, which should be accounted for in the treatment received, new research shows.

In some cases, treating the ADHD might lower the pain, reported Karin Asztély of the Sahlgrenska Academy Institute of Neuroscience, Göteborg, Sweden, and associates. The study was published in the Journal of Pain Research.

The research included 77 Swedish women with ADHD, ASD, or both from a larger prospective longitudinal study. From 2015 to 2018, when the women were aged 19-37 years, they were contacted by mail and phone, and interviewed about symptoms of pain. This included chronic widespread or regional symptoms of pain; widespread pain was pain that lasted more than 3 months and was described both above and below the waist, on both sides of the body, and in the axial skeleton. Any pain that lasted more than 3 months but did not meet those other requirements was listed as chronic regional pain.

Chronic pain of any kind was reported by 59 participants (76.6%). Chronic widespread pain was reported by 25 participants (32.5%), and chronic regional pain was reported by 34 (44.2%), both of which were higher than those seen in a cross-sectional survey, which showed prevalences of 11.9% and 23.9% of Swedish participants, respectively (J Rheumatol. 2001 Jun;28[6]:1369-77).

Among the limitations of the latest study is the small sample size and the absence of healthy controls; however, the researchers thought this was compensated for by the comparisons with previous research.

“Our findings highlight the importance of the health care professionals to address pain problems in this patient group and possible unrecognized ASD and/or ADHD in women with chronic pain,” they concluded.

The investigators reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Asztély et al. J Pain Res. 2019 Oct 18;12:2925-32.

Women with ADHD, autism spectrum disorder (ASD), or both report higher rates of chronic pain, which should be accounted for in the treatment received, new research shows.

In some cases, treating the ADHD might lower the pain, reported Karin Asztély of the Sahlgrenska Academy Institute of Neuroscience, Göteborg, Sweden, and associates. The study was published in the Journal of Pain Research.

The research included 77 Swedish women with ADHD, ASD, or both from a larger prospective longitudinal study. From 2015 to 2018, when the women were aged 19-37 years, they were contacted by mail and phone, and interviewed about symptoms of pain. This included chronic widespread or regional symptoms of pain; widespread pain was pain that lasted more than 3 months and was described both above and below the waist, on both sides of the body, and in the axial skeleton. Any pain that lasted more than 3 months but did not meet those other requirements was listed as chronic regional pain.

Chronic pain of any kind was reported by 59 participants (76.6%). Chronic widespread pain was reported by 25 participants (32.5%), and chronic regional pain was reported by 34 (44.2%), both of which were higher than those seen in a cross-sectional survey, which showed prevalences of 11.9% and 23.9% of Swedish participants, respectively (J Rheumatol. 2001 Jun;28[6]:1369-77).

Among the limitations of the latest study is the small sample size and the absence of healthy controls; however, the researchers thought this was compensated for by the comparisons with previous research.

“Our findings highlight the importance of the health care professionals to address pain problems in this patient group and possible unrecognized ASD and/or ADHD in women with chronic pain,” they concluded.

The investigators reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Asztély et al. J Pain Res. 2019 Oct 18;12:2925-32.

Women with ADHD, autism spectrum disorder (ASD), or both report higher rates of chronic pain, which should be accounted for in the treatment received, new research shows.

In some cases, treating the ADHD might lower the pain, reported Karin Asztély of the Sahlgrenska Academy Institute of Neuroscience, Göteborg, Sweden, and associates. The study was published in the Journal of Pain Research.

The research included 77 Swedish women with ADHD, ASD, or both from a larger prospective longitudinal study. From 2015 to 2018, when the women were aged 19-37 years, they were contacted by mail and phone, and interviewed about symptoms of pain. This included chronic widespread or regional symptoms of pain; widespread pain was pain that lasted more than 3 months and was described both above and below the waist, on both sides of the body, and in the axial skeleton. Any pain that lasted more than 3 months but did not meet those other requirements was listed as chronic regional pain.

Chronic pain of any kind was reported by 59 participants (76.6%). Chronic widespread pain was reported by 25 participants (32.5%), and chronic regional pain was reported by 34 (44.2%), both of which were higher than those seen in a cross-sectional survey, which showed prevalences of 11.9% and 23.9% of Swedish participants, respectively (J Rheumatol. 2001 Jun;28[6]:1369-77).

Among the limitations of the latest study is the small sample size and the absence of healthy controls; however, the researchers thought this was compensated for by the comparisons with previous research.

“Our findings highlight the importance of the health care professionals to address pain problems in this patient group and possible unrecognized ASD and/or ADHD in women with chronic pain,” they concluded.

The investigators reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Asztély et al. J Pain Res. 2019 Oct 18;12:2925-32.

SAN ANTONIO – Patients aged over age 75 years who are hospitalized for management of inflammatory bowel disease have a four to five times greater risk of inpatient mortality than those who are younger, Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.

It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.

Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.

Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.

There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.

Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.

Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.

Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

SAN ANTONIO – Patients aged over age 75 years who are hospitalized for management of inflammatory bowel disease have a four to five times greater risk of inpatient mortality than those who are younger, Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.

It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.

Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.

Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.

There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.

Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.

Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.

Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

SAN ANTONIO – Patients aged over age 75 years who are hospitalized for management of inflammatory bowel disease have a four to five times greater risk of inpatient mortality than those who are younger, Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.

“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.

It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.

Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.

Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.

There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.

Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.

Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.

Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

msullivan@mdedge.com

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

msullivan@mdedge.com

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

msullivan@mdedge.com

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

The Food and Drug Administration has approved acalabrutinib (Calquence) as initial or subsequent treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).

Olivier Le Moal/Getty Images

The approval came as part of Project Orbis, a collaboration among the FDA, the Australian Therapeutic Goods Administration, and Health Canada. The program allows for the concurrent submission of review of oncology drug applications among the various agencies.

Acalabrutinib, a bruton tyrosin kinase inhibitor, is already approved in the United States for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy. The FDA granted breakthrough therapy designation to acalabrutinib as a monotherapy for adults with CLL in August 2019, allowing for an expedited review.

The approval in CLL/SLL was based on results from two randomized clinical trials comparing acalabrutinib with other standard treatments. In the first trial, patients with previously untreated CLL who received acalabrutinib had a longer progression-free survival time, compared with patients who received standard treatment. A similar result was seen in the second trial among patients with previously treated CLL.

The most common adverse events associated with acalabrutinib include anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. Patients receiving the drug should be monitored for symptoms of arrhythmia, serious infection, bleeding, and low blood count. Full prescribing information can be found on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved acalabrutinib (Calquence) as initial or subsequent treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).

Olivier Le Moal/Getty Images

The approval came as part of Project Orbis, a collaboration among the FDA, the Australian Therapeutic Goods Administration, and Health Canada. The program allows for the concurrent submission of review of oncology drug applications among the various agencies.

Acalabrutinib, a bruton tyrosin kinase inhibitor, is already approved in the United States for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy. The FDA granted breakthrough therapy designation to acalabrutinib as a monotherapy for adults with CLL in August 2019, allowing for an expedited review.

The approval in CLL/SLL was based on results from two randomized clinical trials comparing acalabrutinib with other standard treatments. In the first trial, patients with previously untreated CLL who received acalabrutinib had a longer progression-free survival time, compared with patients who received standard treatment. A similar result was seen in the second trial among patients with previously treated CLL.

The most common adverse events associated with acalabrutinib include anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. Patients receiving the drug should be monitored for symptoms of arrhythmia, serious infection, bleeding, and low blood count. Full prescribing information can be found on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved acalabrutinib (Calquence) as initial or subsequent treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).

Olivier Le Moal/Getty Images

The approval came as part of Project Orbis, a collaboration among the FDA, the Australian Therapeutic Goods Administration, and Health Canada. The program allows for the concurrent submission of review of oncology drug applications among the various agencies.

Acalabrutinib, a bruton tyrosin kinase inhibitor, is already approved in the United States for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy. The FDA granted breakthrough therapy designation to acalabrutinib as a monotherapy for adults with CLL in August 2019, allowing for an expedited review.

The approval in CLL/SLL was based on results from two randomized clinical trials comparing acalabrutinib with other standard treatments. In the first trial, patients with previously untreated CLL who received acalabrutinib had a longer progression-free survival time, compared with patients who received standard treatment. A similar result was seen in the second trial among patients with previously treated CLL.

The most common adverse events associated with acalabrutinib include anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. Patients receiving the drug should be monitored for symptoms of arrhythmia, serious infection, bleeding, and low blood count. Full prescribing information can be found on the FDA website.

lfranki@mdedge.com

PHILADELPHIA – Treating patients to a lower LDL target after an ischemic stroke of atherosclerotic origin resulted in fewer recurrent strokes or major cardiovascular events, compared with a higher LDL goal, even though the international trial was stopped early because of lack of funding.

“In the Treat Stroke to Target [TST] trial we showed that the group of patients with an atherosclerotic stroke achieving an LDL cholesterol of less than 70 mg/dL had 22% less recurrent ischemic stroke or other major vascular events than the group achieving a LDL cholesterol between 90 and 110 mg/dL,” lead author Pierre Amarenco, MD, chairman of the department of neurology and the stroke center at Bichat Hospital in Paris, said in an interview.

“We avoided more than one in recurrence in five,” he added.

The findings of the investigator-initiated trial were reported during a late-breaking research session at the American Heart Association scientific sessions and simultaneously published online Nov. 18 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1910355).

Discussant Mitchell S.V. Elkind, MD, president-elect of the American Heart Association, called the TST findings “practice confirming” of a strategy many cardiologists already follow for stroke patients.

“The TST study is only the second trial that was done in neurology for stroke prevention using statins and lipid-lowering therapy, and that’s what makes it a hopeful and real advance,” he said in an interview.

To achieve the LDL-lowering goal, two-thirds of patients received a high-dose statin therapy while the remainder received both high-dose statin and ezetimibe (Zetia, Merck). There were no significant increases in intracranial hemorrhage observed between lower- and higher-target groups.

“Now guidelines should move to recommending a target LDL cholesterol of less than 70 mg/dL in all patients with a proven ischemic stroke of atherosclerotic origin,” said Dr. Amarenco, who is also a professor of neurology at Denis Diderot Paris University.

Rare lipid study following stroke

American Heart Association/American Stroke Association guidelines recommend intense statin therapy after an atherothrombotic stroke “but no target level is given to the practitioners,” Dr. Amarenco said. “In reality, most patients receive a reduced dose of statin.”

For example, despite 70% of patients receiving a statin, the average LDL cholesterol level was 92 mg/dL in a real-world registry.

The TST trial is the first major study to evaluate treating to target LDL levels in the ischemic stroke population since the SPARCL trial in 2006. SPARCL was the first randomized, controlled clinical trial to evaluate whether daily statin therapy could reduce the risk of stroke in patients who had suffered a stroke or transient ischemic attack (TIA).

SPARCL demonstrated a 16% risk reduction with atorvastatin 80 mg daily versus placebo, and further risk reduction of 33% among those with carotid stenosis, over 5 years. There was some concern about safety for a time; post-hoc analysis showed what appeared to be an increased risk for intracranial hemorrhage with statin treatment. Subsequent analyses seemed to suggest the finding may have been a chance one, however.

For the TST study, Dr. Amarenco and colleagues enrolled participants between March 2010 and December 2018 at one of 61 centers in France. In 2015, the study expanded to include 16 sites in South Korea.

Investigators evaluated participants after an ischemic stroke or a TIA with evidence of atherosclerosis. Blood pressure, smoking cessation, and diabetes were well controlled, he said.

Dr. Amarenco and colleagues randomly assigned 1,430 participants to the low–LDL cholesterol target group, less than 70 mg/dL, and another 1,430 to a high-LDL group with a target of 100 mg/dL.

Assessments were every 6 months and up to 1 year after the last patient joined the study.

Treatment with any available statin on the market was allowed. Ezetimibe could be added on top of statin therapy as necessary. A total of 55% were statin naive at study entry.

Study stopped early

The trial was stopped in May 2019 after allocated funds ran out. At this point, researchers had 277 events to analyze, although their initial goal was to reach 385.

The primary endpoint of this event-driven trial was a composite of nonfatal stroke, nonfatal MI, and unstable angina followed by urgent coronary revascularization; TIA followed by urgent carotid revascularization; or cardiovascular death, including sudden deaths.

The endpoint was experienced by 8.5% of participants in the lower-target group versus 10.9% of those in the higher-target group. This translated to a 22% relative risk reduction (adjusted hazard ratio, 0.78; 95% confidence interval, 0.68-0.98; P =.04).

A total of 86% of participants had an ischemic stroke confirmed by brain MRI or CT scan. In this group, the relative risk reduction was 33% – “meaning that we could avoid one-third of recurrent major vascular events,” Dr. Amarenco said.

Furthermore, targeting the lower LDL levels was associated with a relative risk reduction of 40% among those with diabetes.

Secondary outcomes not significant

The investigators used hierarchical testing to compare two outcomes at a time in a prespecified order. They planned to continue this strategy until a comparison emerged as nonsignificant.

This occurred right away when their first composite secondary endpoint comparison between nonfatal MI and urgent revascularization was found to be not significantly different between groups (P = .12).

The early ending “weakened the results of the trial, and the results should be taken with caution because of that,” Dr. Amarenco said.

In addition, the number of hemorrhagic strokes did not differ significantly between groups. There were 18 of these events in the lower-target group and 13 in the higher-target cohort.

That numerical increase in intracranial hemorrhage was “driven by the Korean patients. … and that is something we will report soon,” Dr. Amarenco said.

Interestingly, the researchers also evaluated how much time participants spent within the target LDL cholesterol range, averaged by study site. They found that 53% of the lower–LDL target group, for example, was in the therapeutic range on average during the study.

When Dr. Amarenco and colleagues looked at participants who managed to spend 50%-100% in the target range, the relative risk reduction was 36%.

“So we can hypothesize that, if we had used a more potent drug like PCSK9 inhibitors to be closer to 100% in the therapeutic range, we may have had a greater effect size,” Dr. Amarenco said.

“Our results suggest that LDL cholesterol is causally related to atherosclerosis and confirm that the lower the LDL cholesterol the better,” Dr. Amarenco said.

“Future trials should explore the efficacy and safety of lowering LDL cholesterol to very low levels such as less than 55 mg/dL or even 30 mg/dL (as obtained in the FOURIER trial) by using PCSK9 inhibitors or equivalent in patients with an ischemic stroke due to atherosclerotic disease,” Dr. Amarenco said.

‘Practice-confirming’ findings

The findings are also in line with secondary analyses of the WASID (Neurology. 1995 Aug;45[8]:1488-93) and SAMMPRIS trials, which should dispel some concerns that persist about taking LDL to such low levels that it increases risk of intracerebral hemorrhage, Dr. Amarenco noted.

However, TST, he said, didn’t provide clear answers on what specific subgroups of patients with a stroke history would benefit from aggressive lipid lowering.

“What is stroke without atherosclerotic disease?” he said. “Some people say small-vessel disease is also a form of atherosclerosis, and most patients with atrial fibrillation, which is increasingly recognized as a cause of stroke, are also going to have atherosclerosis of the heart as well as the brain and blood vessels.

“Many, many stroke patients will fall into this category,” Dr. Elkind said, “and the question is, should they be treated more aggressively with lipid lowering?”

“The results of this study fit pretty nicely into the rubric of the AHA cholesterol guidelines,” said Donald M. Lloyd-Jones, MD, chairman, department of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago, and chair of the AHA’s 2019 Council on Scientific Sessions Programming. Dr. Lloyd-Jones was also a member of the guideline committee.

Stroke patients are not “garden variety coronary patients,” he said. “The concern about intracerebral hemorrhage continues to be something that we wonder about: Should we be driving our stroke patients as low as our coronary patients? I think these data will certainly help us.”

Consideration for future guidelines

The study would have been more helpful if it provided more detail about the treatment regimens used, Jennifer Robinson, MD, director of the prevention intervention center, department of epidemiology, University of Iowa, said in an interview.

“What was the dose intensity of statins the patients were on?” Dr. Robinson said. “Part of our struggle has been to convince people to use high-intensity statins – get the maximum from statins that are generic now and cost saving in even very low-risk primary prevention patients.”

She said that a third of patients in TST also took ezetimibe with the statin “makes sense” because of its generic status.

Nonetheless, Dr. Robinson said, TST adds to the evidence that LDL of 100 mg/dL is not good enough, that high-intensity statin therapy is superior to a moderate regimen and that adding a nonstatin – ezetimibe in TST – can derive added benefit.

The TST findings may give guideline writers direction going forward, she said. “We really need to start thinking about the potential for net benefit from added therapy, whether it’s from intensifying LDL lowering, adding icosapent ethyl (Vascepa, Amarin), which seems to have remarkable benefits, or SGLT2 inhibitor,” she said.

“There are a lot of options,” Dr. Robinson said. “We need to have an outlook beyond just treating to target with what really is the best maximized accepted therapy.”

TST was funded primarily by French Government, but also with grants from Pfizer, Astra Zeneca and Merck. Dr. Amarenco disclosed that he is a consultant or advisor to Modest, Sanofi, Bristol-Myers Squibb, and Amgen; receives honoraria from Modest, Amgen, Kowa, Shing Poon, Kowa, Bayer, GSK, Fibrogen, and AstraZeneca. He also receives research grants from Pfizer, Astra Zeneca, Sanofi, BMS, Merck, Boston Scientific, and the French Government.

This article also appears on Medscape.com.

SOURCE: Amarenco P. ACC 2019, Late Breaking Science 6 session.

PHILADELPHIA – Treating patients to a lower LDL target after an ischemic stroke of atherosclerotic origin resulted in fewer recurrent strokes or major cardiovascular events, compared with a higher LDL goal, even though the international trial was stopped early because of lack of funding.

“In the Treat Stroke to Target [TST] trial we showed that the group of patients with an atherosclerotic stroke achieving an LDL cholesterol of less than 70 mg/dL had 22% less recurrent ischemic stroke or other major vascular events than the group achieving a LDL cholesterol between 90 and 110 mg/dL,” lead author Pierre Amarenco, MD, chairman of the department of neurology and the stroke center at Bichat Hospital in Paris, said in an interview.

“We avoided more than one in recurrence in five,” he added.

The findings of the investigator-initiated trial were reported during a late-breaking research session at the American Heart Association scientific sessions and simultaneously published online Nov. 18 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1910355).

Discussant Mitchell S.V. Elkind, MD, president-elect of the American Heart Association, called the TST findings “practice confirming” of a strategy many cardiologists already follow for stroke patients.

“The TST study is only the second trial that was done in neurology for stroke prevention using statins and lipid-lowering therapy, and that’s what makes it a hopeful and real advance,” he said in an interview.

To achieve the LDL-lowering goal, two-thirds of patients received a high-dose statin therapy while the remainder received both high-dose statin and ezetimibe (Zetia, Merck). There were no significant increases in intracranial hemorrhage observed between lower- and higher-target groups.

“Now guidelines should move to recommending a target LDL cholesterol of less than 70 mg/dL in all patients with a proven ischemic stroke of atherosclerotic origin,” said Dr. Amarenco, who is also a professor of neurology at Denis Diderot Paris University.

Rare lipid study following stroke

American Heart Association/American Stroke Association guidelines recommend intense statin therapy after an atherothrombotic stroke “but no target level is given to the practitioners,” Dr. Amarenco said. “In reality, most patients receive a reduced dose of statin.”

For example, despite 70% of patients receiving a statin, the average LDL cholesterol level was 92 mg/dL in a real-world registry.

The TST trial is the first major study to evaluate treating to target LDL levels in the ischemic stroke population since the SPARCL trial in 2006. SPARCL was the first randomized, controlled clinical trial to evaluate whether daily statin therapy could reduce the risk of stroke in patients who had suffered a stroke or transient ischemic attack (TIA).

SPARCL demonstrated a 16% risk reduction with atorvastatin 80 mg daily versus placebo, and further risk reduction of 33% among those with carotid stenosis, over 5 years. There was some concern about safety for a time; post-hoc analysis showed what appeared to be an increased risk for intracranial hemorrhage with statin treatment. Subsequent analyses seemed to suggest the finding may have been a chance one, however.

For the TST study, Dr. Amarenco and colleagues enrolled participants between March 2010 and December 2018 at one of 61 centers in France. In 2015, the study expanded to include 16 sites in South Korea.

Investigators evaluated participants after an ischemic stroke or a TIA with evidence of atherosclerosis. Blood pressure, smoking cessation, and diabetes were well controlled, he said.

Dr. Amarenco and colleagues randomly assigned 1,430 participants to the low–LDL cholesterol target group, less than 70 mg/dL, and another 1,430 to a high-LDL group with a target of 100 mg/dL.

Assessments were every 6 months and up to 1 year after the last patient joined the study.

Treatment with any available statin on the market was allowed. Ezetimibe could be added on top of statin therapy as necessary. A total of 55% were statin naive at study entry.

Study stopped early

The trial was stopped in May 2019 after allocated funds ran out. At this point, researchers had 277 events to analyze, although their initial goal was to reach 385.

The primary endpoint of this event-driven trial was a composite of nonfatal stroke, nonfatal MI, and unstable angina followed by urgent coronary revascularization; TIA followed by urgent carotid revascularization; or cardiovascular death, including sudden deaths.

The endpoint was experienced by 8.5% of participants in the lower-target group versus 10.9% of those in the higher-target group. This translated to a 22% relative risk reduction (adjusted hazard ratio, 0.78; 95% confidence interval, 0.68-0.98; P =.04).

A total of 86% of participants had an ischemic stroke confirmed by brain MRI or CT scan. In this group, the relative risk reduction was 33% – “meaning that we could avoid one-third of recurrent major vascular events,” Dr. Amarenco said.

Furthermore, targeting the lower LDL levels was associated with a relative risk reduction of 40% among those with diabetes.

Secondary outcomes not significant

The investigators used hierarchical testing to compare two outcomes at a time in a prespecified order. They planned to continue this strategy until a comparison emerged as nonsignificant.

This occurred right away when their first composite secondary endpoint comparison between nonfatal MI and urgent revascularization was found to be not significantly different between groups (P = .12).

The early ending “weakened the results of the trial, and the results should be taken with caution because of that,” Dr. Amarenco said.

In addition, the number of hemorrhagic strokes did not differ significantly between groups. There were 18 of these events in the lower-target group and 13 in the higher-target cohort.

That numerical increase in intracranial hemorrhage was “driven by the Korean patients. … and that is something we will report soon,” Dr. Amarenco said.

Interestingly, the researchers also evaluated how much time participants spent within the target LDL cholesterol range, averaged by study site. They found that 53% of the lower–LDL target group, for example, was in the therapeutic range on average during the study.

When Dr. Amarenco and colleagues looked at participants who managed to spend 50%-100% in the target range, the relative risk reduction was 36%.

“So we can hypothesize that, if we had used a more potent drug like PCSK9 inhibitors to be closer to 100% in the therapeutic range, we may have had a greater effect size,” Dr. Amarenco said.

“Our results suggest that LDL cholesterol is causally related to atherosclerosis and confirm that the lower the LDL cholesterol the better,” Dr. Amarenco said.

“Future trials should explore the efficacy and safety of lowering LDL cholesterol to very low levels such as less than 55 mg/dL or even 30 mg/dL (as obtained in the FOURIER trial) by using PCSK9 inhibitors or equivalent in patients with an ischemic stroke due to atherosclerotic disease,” Dr. Amarenco said.

‘Practice-confirming’ findings

The findings are also in line with secondary analyses of the WASID (Neurology. 1995 Aug;45[8]:1488-93) and SAMMPRIS trials, which should dispel some concerns that persist about taking LDL to such low levels that it increases risk of intracerebral hemorrhage, Dr. Amarenco noted.

However, TST, he said, didn’t provide clear answers on what specific subgroups of patients with a stroke history would benefit from aggressive lipid lowering.

“What is stroke without atherosclerotic disease?” he said. “Some people say small-vessel disease is also a form of atherosclerosis, and most patients with atrial fibrillation, which is increasingly recognized as a cause of stroke, are also going to have atherosclerosis of the heart as well as the brain and blood vessels.

“Many, many stroke patients will fall into this category,” Dr. Elkind said, “and the question is, should they be treated more aggressively with lipid lowering?”

“The results of this study fit pretty nicely into the rubric of the AHA cholesterol guidelines,” said Donald M. Lloyd-Jones, MD, chairman, department of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago, and chair of the AHA’s 2019 Council on Scientific Sessions Programming. Dr. Lloyd-Jones was also a member of the guideline committee.

Stroke patients are not “garden variety coronary patients,” he said. “The concern about intracerebral hemorrhage continues to be something that we wonder about: Should we be driving our stroke patients as low as our coronary patients? I think these data will certainly help us.”

Consideration for future guidelines

The study would have been more helpful if it provided more detail about the treatment regimens used, Jennifer Robinson, MD, director of the prevention intervention center, department of epidemiology, University of Iowa, said in an interview.

“What was the dose intensity of statins the patients were on?” Dr. Robinson said. “Part of our struggle has been to convince people to use high-intensity statins – get the maximum from statins that are generic now and cost saving in even very low-risk primary prevention patients.”

She said that a third of patients in TST also took ezetimibe with the statin “makes sense” because of its generic status.

Nonetheless, Dr. Robinson said, TST adds to the evidence that LDL of 100 mg/dL is not good enough, that high-intensity statin therapy is superior to a moderate regimen and that adding a nonstatin – ezetimibe in TST – can derive added benefit.

The TST findings may give guideline writers direction going forward, she said. “We really need to start thinking about the potential for net benefit from added therapy, whether it’s from intensifying LDL lowering, adding icosapent ethyl (Vascepa, Amarin), which seems to have remarkable benefits, or SGLT2 inhibitor,” she said.

“There are a lot of options,” Dr. Robinson said. “We need to have an outlook beyond just treating to target with what really is the best maximized accepted therapy.”

TST was funded primarily by French Government, but also with grants from Pfizer, Astra Zeneca and Merck. Dr. Amarenco disclosed that he is a consultant or advisor to Modest, Sanofi, Bristol-Myers Squibb, and Amgen; receives honoraria from Modest, Amgen, Kowa, Shing Poon, Kowa, Bayer, GSK, Fibrogen, and AstraZeneca. He also receives research grants from Pfizer, Astra Zeneca, Sanofi, BMS, Merck, Boston Scientific, and the French Government.

This article also appears on Medscape.com.

SOURCE: Amarenco P. ACC 2019, Late Breaking Science 6 session.

PHILADELPHIA – Treating patients to a lower LDL target after an ischemic stroke of atherosclerotic origin resulted in fewer recurrent strokes or major cardiovascular events, compared with a higher LDL goal, even though the international trial was stopped early because of lack of funding.

“In the Treat Stroke to Target [TST] trial we showed that the group of patients with an atherosclerotic stroke achieving an LDL cholesterol of less than 70 mg/dL had 22% less recurrent ischemic stroke or other major vascular events than the group achieving a LDL cholesterol between 90 and 110 mg/dL,” lead author Pierre Amarenco, MD, chairman of the department of neurology and the stroke center at Bichat Hospital in Paris, said in an interview.

“We avoided more than one in recurrence in five,” he added.

The findings of the investigator-initiated trial were reported during a late-breaking research session at the American Heart Association scientific sessions and simultaneously published online Nov. 18 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1910355).

Discussant Mitchell S.V. Elkind, MD, president-elect of the American Heart Association, called the TST findings “practice confirming” of a strategy many cardiologists already follow for stroke patients.

“The TST study is only the second trial that was done in neurology for stroke prevention using statins and lipid-lowering therapy, and that’s what makes it a hopeful and real advance,” he said in an interview.

To achieve the LDL-lowering goal, two-thirds of patients received a high-dose statin therapy while the remainder received both high-dose statin and ezetimibe (Zetia, Merck). There were no significant increases in intracranial hemorrhage observed between lower- and higher-target groups.

“Now guidelines should move to recommending a target LDL cholesterol of less than 70 mg/dL in all patients with a proven ischemic stroke of atherosclerotic origin,” said Dr. Amarenco, who is also a professor of neurology at Denis Diderot Paris University.

Rare lipid study following stroke

American Heart Association/American Stroke Association guidelines recommend intense statin therapy after an atherothrombotic stroke “but no target level is given to the practitioners,” Dr. Amarenco said. “In reality, most patients receive a reduced dose of statin.”

For example, despite 70% of patients receiving a statin, the average LDL cholesterol level was 92 mg/dL in a real-world registry.

The TST trial is the first major study to evaluate treating to target LDL levels in the ischemic stroke population since the SPARCL trial in 2006. SPARCL was the first randomized, controlled clinical trial to evaluate whether daily statin therapy could reduce the risk of stroke in patients who had suffered a stroke or transient ischemic attack (TIA).

SPARCL demonstrated a 16% risk reduction with atorvastatin 80 mg daily versus placebo, and further risk reduction of 33% among those with carotid stenosis, over 5 years. There was some concern about safety for a time; post-hoc analysis showed what appeared to be an increased risk for intracranial hemorrhage with statin treatment. Subsequent analyses seemed to suggest the finding may have been a chance one, however.

For the TST study, Dr. Amarenco and colleagues enrolled participants between March 2010 and December 2018 at one of 61 centers in France. In 2015, the study expanded to include 16 sites in South Korea.

Investigators evaluated participants after an ischemic stroke or a TIA with evidence of atherosclerosis. Blood pressure, smoking cessation, and diabetes were well controlled, he said.

Dr. Amarenco and colleagues randomly assigned 1,430 participants to the low–LDL cholesterol target group, less than 70 mg/dL, and another 1,430 to a high-LDL group with a target of 100 mg/dL.

Assessments were every 6 months and up to 1 year after the last patient joined the study.

Treatment with any available statin on the market was allowed. Ezetimibe could be added on top of statin therapy as necessary. A total of 55% were statin naive at study entry.

Study stopped early

The trial was stopped in May 2019 after allocated funds ran out. At this point, researchers had 277 events to analyze, although their initial goal was to reach 385.

The primary endpoint of this event-driven trial was a composite of nonfatal stroke, nonfatal MI, and unstable angina followed by urgent coronary revascularization; TIA followed by urgent carotid revascularization; or cardiovascular death, including sudden deaths.

The endpoint was experienced by 8.5% of participants in the lower-target group versus 10.9% of those in the higher-target group. This translated to a 22% relative risk reduction (adjusted hazard ratio, 0.78; 95% confidence interval, 0.68-0.98; P =.04).

A total of 86% of participants had an ischemic stroke confirmed by brain MRI or CT scan. In this group, the relative risk reduction was 33% – “meaning that we could avoid one-third of recurrent major vascular events,” Dr. Amarenco said.

Furthermore, targeting the lower LDL levels was associated with a relative risk reduction of 40% among those with diabetes.

Secondary outcomes not significant

The investigators used hierarchical testing to compare two outcomes at a time in a prespecified order. They planned to continue this strategy until a comparison emerged as nonsignificant.

This occurred right away when their first composite secondary endpoint comparison between nonfatal MI and urgent revascularization was found to be not significantly different between groups (P = .12).

The early ending “weakened the results of the trial, and the results should be taken with caution because of that,” Dr. Amarenco said.

In addition, the number of hemorrhagic strokes did not differ significantly between groups. There were 18 of these events in the lower-target group and 13 in the higher-target cohort.

That numerical increase in intracranial hemorrhage was “driven by the Korean patients. … and that is something we will report soon,” Dr. Amarenco said.

Interestingly, the researchers also evaluated how much time participants spent within the target LDL cholesterol range, averaged by study site. They found that 53% of the lower–LDL target group, for example, was in the therapeutic range on average during the study.

When Dr. Amarenco and colleagues looked at participants who managed to spend 50%-100% in the target range, the relative risk reduction was 36%.

“So we can hypothesize that, if we had used a more potent drug like PCSK9 inhibitors to be closer to 100% in the therapeutic range, we may have had a greater effect size,” Dr. Amarenco said.

“Our results suggest that LDL cholesterol is causally related to atherosclerosis and confirm that the lower the LDL cholesterol the better,” Dr. Amarenco said.

“Future trials should explore the efficacy and safety of lowering LDL cholesterol to very low levels such as less than 55 mg/dL or even 30 mg/dL (as obtained in the FOURIER trial) by using PCSK9 inhibitors or equivalent in patients with an ischemic stroke due to atherosclerotic disease,” Dr. Amarenco said.

‘Practice-confirming’ findings

The findings are also in line with secondary analyses of the WASID (Neurology. 1995 Aug;45[8]:1488-93) and SAMMPRIS trials, which should dispel some concerns that persist about taking LDL to such low levels that it increases risk of intracerebral hemorrhage, Dr. Amarenco noted.

However, TST, he said, didn’t provide clear answers on what specific subgroups of patients with a stroke history would benefit from aggressive lipid lowering.

“What is stroke without atherosclerotic disease?” he said. “Some people say small-vessel disease is also a form of atherosclerosis, and most patients with atrial fibrillation, which is increasingly recognized as a cause of stroke, are also going to have atherosclerosis of the heart as well as the brain and blood vessels.

“Many, many stroke patients will fall into this category,” Dr. Elkind said, “and the question is, should they be treated more aggressively with lipid lowering?”

“The results of this study fit pretty nicely into the rubric of the AHA cholesterol guidelines,” said Donald M. Lloyd-Jones, MD, chairman, department of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago, and chair of the AHA’s 2019 Council on Scientific Sessions Programming. Dr. Lloyd-Jones was also a member of the guideline committee.

Stroke patients are not “garden variety coronary patients,” he said. “The concern about intracerebral hemorrhage continues to be something that we wonder about: Should we be driving our stroke patients as low as our coronary patients? I think these data will certainly help us.”

Consideration for future guidelines

The study would have been more helpful if it provided more detail about the treatment regimens used, Jennifer Robinson, MD, director of the prevention intervention center, department of epidemiology, University of Iowa, said in an interview.

“What was the dose intensity of statins the patients were on?” Dr. Robinson said. “Part of our struggle has been to convince people to use high-intensity statins – get the maximum from statins that are generic now and cost saving in even very low-risk primary prevention patients.”

She said that a third of patients in TST also took ezetimibe with the statin “makes sense” because of its generic status.

Nonetheless, Dr. Robinson said, TST adds to the evidence that LDL of 100 mg/dL is not good enough, that high-intensity statin therapy is superior to a moderate regimen and that adding a nonstatin – ezetimibe in TST – can derive added benefit.

The TST findings may give guideline writers direction going forward, she said. “We really need to start thinking about the potential for net benefit from added therapy, whether it’s from intensifying LDL lowering, adding icosapent ethyl (Vascepa, Amarin), which seems to have remarkable benefits, or SGLT2 inhibitor,” she said.

“There are a lot of options,” Dr. Robinson said. “We need to have an outlook beyond just treating to target with what really is the best maximized accepted therapy.”

TST was funded primarily by French Government, but also with grants from Pfizer, Astra Zeneca and Merck. Dr. Amarenco disclosed that he is a consultant or advisor to Modest, Sanofi, Bristol-Myers Squibb, and Amgen; receives honoraria from Modest, Amgen, Kowa, Shing Poon, Kowa, Bayer, GSK, Fibrogen, and AstraZeneca. He also receives research grants from Pfizer, Astra Zeneca, Sanofi, BMS, Merck, Boston Scientific, and the French Government.

This article also appears on Medscape.com.

SOURCE: Amarenco P. ACC 2019, Late Breaking Science 6 session.

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

The Diagnosis: Actinic Comedonal Plaque  

Histopathologic examination showed multiple small, keratin-filled cystic spaces in the superficial dermis lined by stratified squamous epithelium that keratinized with a granular layer with surrounding solar elastosis (Figure 1). These findings were consistent with an actinic comedonal plaque (ACP), a rare variant of Favre-Racouchot syndrome (FRS). Due to other cases of invasive squamous cell carcinomas developing within these lesions¹ and the patient's history of basal cell carcinoma in the area, it was important to rule out malignancy and further confirm the diagnosis. Thus, an additional biopsy was obtained, which revealed no sign of cellular atypia. The patient was bothered by the appearance and texture of the lesion, so he elected to pursue treatment. Because of the lesion's moderate size and location, surgical excision was not recommended. He was treated with cryosurgery followed by tretinoin gel 0.025% for 3 months (Figure 2). At 1-year follow-up, there was no recurrence and an acceptable cosmetic outcome.  

Actinic comedonal plaques are characterized by cysts, comedones, and papules that form well-defined yellow plaques on the skin after chronic sun exposure.² First described in 1980 by Eastern and Martin,³ these lesions are most often found on the neck, thorax, nasal dorsum, helix, and forearms; they often are mistaken for basal cell carcinomas, chondrodermatitis nodularis chronica helicis, and amyloidosis.^2,4 

Similar to the cases described by Eastern and Martin,³ our patient presented with a solitary 2.8×1.6-cm yellowish and bumpy plaque that was growing on chronically sun-exposed skin of the medial right cheek. The patient's history of smoking and basal cell carcinoma removal led to the following differential diagnoses: recurrent malignancy, tumors of dermal appendages, and xanthelasmalike deposition within a scar, among others.  

Histologic examination demonstrated keratin-filled cystic spaces in the superficial dermis, along with hyperkeratosis and solar elastosis. These findings were consistent with the original histologic descriptions of ACP that were cited as a rare ectopic form of FRS.⁵ Leeuwis-Fedorovich et al¹ described multifocal squamous cell carcinomas arising in a FRS lesion in 2 cases. Additional biopsy was performed in our patient to rule out this possibility. 

Aside from its role in dermatologic malignancy, exposure to UV light can lead to dilation of the sebaceous gland infundibulum and formation of comedones in various locations.² Histologically, lesions of ACP feature dilated, keratin-filled follicles within a matrix of amorphous damaged collagen in the middle and lower dermis, along with elastosis and basophilic degeneration with fragmentation of collagen bundles in the upper dermis coated with flattened epidermis.^2,3  

Several clinical diagnoses were considered in the differential for our patient. In contrast to our patient's solitary lesion, classic FRS--nodular elastosis with cysts and comedones--is characterized by a diffuse yellowish hue of large open black comedones that are symmetrically distributed on the temporal and periorbital areas.⁶  

Xanthoma has several clinical presentations. Plane xanthomas typically develop in skin folds, especially in palmar creases, while xanthelasma typically consists of yellow soft plaques on the eyelids and periorbital skin. Histologically, xanthomas contain lipid-laden macrophages, which were absent in our patient.⁷ 

Cutaneous amyloidosis can be characterized as macular, papular, and nodular. Nodular, the rarest subtype, commonly manifests on the face.⁸ However, its characteristic histologic features include atrophic epidermal changes with an amorphous, eosinophilic-appearing dermis due to amyloid deposition. These findings were absent in our case.  

Recurrent neoplasm would be in the differential diagnosis of any solitary nodule arising within a previously treated site of malignancy, which was excluded by histologic examination of our patient.⁷ 

Topical tretinoin has been demonstrated as effective treatment of both FRS and ACP.^2,9 Other effective treatment modalities include cryotherapy and photoprotection.⁹ For our patient, a combination of cryosurgery and topical tretinoin resulted in depression of the plaque and a good cosmetic outcome. 
 
Acknowledgments
We thank the patient for granting permission to publish this article. We also are indebted to Morgan L. Wilson, MD (Springfield, Illinois), for his expert dermatopathologic evaluation in this case. He has received no compensation for his contribution.  
 

PHILADELPHIA – Coronary revascularization in patients with stage 4 or 5 chronic kidney disease (CKD) and stable ischemic heart disease accomplishes nothing constructive, according to clear-cut results of the landmark ISCHEMIA-CKD trial.

In this multinational randomized trial including 777 stable patients with advanced CKD and moderate or severe myocardial ischemia on noninvasive testing, an early invasive strategy didn’t reduce the risks of death or ischemic events, didn’t provide any significant improvement in quality of life metrics, and resulted in an increased risk of stroke, Sripal Bangalore, MD, reported at the American Heart Association scientific sessions.

“Overall, an initial invasive strategy did not demonstrate a reduced risk of clinical outcomes as compared with an initial conservative strategy,” said Dr. Bangalore, professor of medicine and director of complex coronary intervention at New York University.

This was easily the largest-ever trial of an invasive versus conservative coronary artery disease management strategy in this challenging population. For example, in the COURAGE trial of optimal medical therapy with or without percutaneous coronary intervention for stable coronary disease (N Engl J Med. 2007 Apr 12;356[15]:1503-16), only 16 of the 2,287 participants had an estimated glomerular filtration rate below 30 mL/min per 1.73 m².

Of note, the participating study sites received special training aimed at minimizing the risk of acute kidney injury after cardiac catheterization in this at-risk population. The training included utilization of a customized left ventricular end diastolic volume–based hydration protocol, guidance on how to perform percutaneous coronary intervention with little or no contrast material, and encouragement of a heart/kidney team approach involving a cardiologist, nephrologist, and cardiovascular surgeon. This training really paid off, with roughly a 7% incidence of acute kidney injury after catheterization.

“The expected rate in such patients would be 30%-60%,” according to Dr. Bangalore.

The primary endpoint in ISCHEMIA-CKD was the rates of death or MI during 3 years of prospective follow-up. This occurred in 36.7% of patients randomized to optimal medical therapy alone and 36.4% of those randomized to an early invasive strategy. Similarly, the major secondary endpoint, comprising death, MI, and hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, was also a virtual dead heat, occurring in about 39% of subjects. More than 27% of study participants had died by the 3-year mark regardless of how their coronary disease was managed.

The adjusted risk of stroke was 3.76-fold higher in the invasive strategy group; however, the most strokes were not procedurally related, and the explanation for the significantly increased risk in the invasively managed group remains unknown, the cardiologist said.

John A. Spertus, MD, who led the quality of life assessment in ISCHEMIA-CKD and in the 5,129-patient parent ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), also presented at the AHA scientific sessions. He reported that, unlike in the parent study, there was no hint of a meaningful long-term quality of life benefit for revascularization plus optimal medical therapy, compared with that of optimal medical therapy alone, in ISCHEMIA-CKD.

“We have greater than 93% confidence that there is more of a quality of life effect in patients without advanced CKD than in patients with advanced CKD,” said Dr. Spertus, director of health outcomes research at the Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri, Kansas City.

Discussant Glenn L. Levine, MD, hailed ISCHEMIA-CKD as “a monumental achievement,” an ambitious, well-powered study with essentially no loss of follow-up during up to 4 years. It helps fill an utter void in the AHA/American College of Cardiology guidelines, which to date offer no recommendations at all regarding revascularization in patients with CKD because of a lack of evidence. And he considers ISCHEMIA-CKD to be unequivocally practice changing and guideline changing.

“Based on the results of ISCHEMIA-CKD, I will generally not go searching for ischemia and [coronary artery disease] in most severe and end-stage CKD patients, absent marked or unacceptable angina, and will treat them with medical therapy alone,” declared Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center, both in Houston.

He offered a few caveats. Excluded from participation in ISCHEMIA-CKD were patients with acute coronary syndrome, significant heart failure, or unacceptable angina despite optimal medical therapy at baseline, so the study results don’t apply to them. Also, the acute kidney injury rate after intervention was eye-catchingly low.

Dr. Bangalore discussed the ISCHEMIA-CKD trial and outcomes in a video interview with Medscape’s Tricia Ward.

“It seems unlikely that all centers routinely do and will exactly follow the very careful measures to limit contrast and minimize contrast nephropathy used in this study,” Dr. Levine commented.

ISCHEMIA-CKD, like its parent ISCHEMIA trial, was funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore reported having no relevant financial interests. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire, which was used for quality of life measurement in the trials. Dr. Levine disclosed that he has no relations with industry or conflicts of interest.

bjancin@mdedge.com

PHILADELPHIA – Coronary revascularization in patients with stage 4 or 5 chronic kidney disease (CKD) and stable ischemic heart disease accomplishes nothing constructive, according to clear-cut results of the landmark ISCHEMIA-CKD trial.

In this multinational randomized trial including 777 stable patients with advanced CKD and moderate or severe myocardial ischemia on noninvasive testing, an early invasive strategy didn’t reduce the risks of death or ischemic events, didn’t provide any significant improvement in quality of life metrics, and resulted in an increased risk of stroke, Sripal Bangalore, MD, reported at the American Heart Association scientific sessions.

“Overall, an initial invasive strategy did not demonstrate a reduced risk of clinical outcomes as compared with an initial conservative strategy,” said Dr. Bangalore, professor of medicine and director of complex coronary intervention at New York University.

This was easily the largest-ever trial of an invasive versus conservative coronary artery disease management strategy in this challenging population. For example, in the COURAGE trial of optimal medical therapy with or without percutaneous coronary intervention for stable coronary disease (N Engl J Med. 2007 Apr 12;356[15]:1503-16), only 16 of the 2,287 participants had an estimated glomerular filtration rate below 30 mL/min per 1.73 m².

Of note, the participating study sites received special training aimed at minimizing the risk of acute kidney injury after cardiac catheterization in this at-risk population. The training included utilization of a customized left ventricular end diastolic volume–based hydration protocol, guidance on how to perform percutaneous coronary intervention with little or no contrast material, and encouragement of a heart/kidney team approach involving a cardiologist, nephrologist, and cardiovascular surgeon. This training really paid off, with roughly a 7% incidence of acute kidney injury after catheterization.

“The expected rate in such patients would be 30%-60%,” according to Dr. Bangalore.

The primary endpoint in ISCHEMIA-CKD was the rates of death or MI during 3 years of prospective follow-up. This occurred in 36.7% of patients randomized to optimal medical therapy alone and 36.4% of those randomized to an early invasive strategy. Similarly, the major secondary endpoint, comprising death, MI, and hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, was also a virtual dead heat, occurring in about 39% of subjects. More than 27% of study participants had died by the 3-year mark regardless of how their coronary disease was managed.

The adjusted risk of stroke was 3.76-fold higher in the invasive strategy group; however, the most strokes were not procedurally related, and the explanation for the significantly increased risk in the invasively managed group remains unknown, the cardiologist said.

John A. Spertus, MD, who led the quality of life assessment in ISCHEMIA-CKD and in the 5,129-patient parent ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), also presented at the AHA scientific sessions. He reported that, unlike in the parent study, there was no hint of a meaningful long-term quality of life benefit for revascularization plus optimal medical therapy, compared with that of optimal medical therapy alone, in ISCHEMIA-CKD.

“We have greater than 93% confidence that there is more of a quality of life effect in patients without advanced CKD than in patients with advanced CKD,” said Dr. Spertus, director of health outcomes research at the Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri, Kansas City.

Discussant Glenn L. Levine, MD, hailed ISCHEMIA-CKD as “a monumental achievement,” an ambitious, well-powered study with essentially no loss of follow-up during up to 4 years. It helps fill an utter void in the AHA/American College of Cardiology guidelines, which to date offer no recommendations at all regarding revascularization in patients with CKD because of a lack of evidence. And he considers ISCHEMIA-CKD to be unequivocally practice changing and guideline changing.

“Based on the results of ISCHEMIA-CKD, I will generally not go searching for ischemia and [coronary artery disease] in most severe and end-stage CKD patients, absent marked or unacceptable angina, and will treat them with medical therapy alone,” declared Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center, both in Houston.

He offered a few caveats. Excluded from participation in ISCHEMIA-CKD were patients with acute coronary syndrome, significant heart failure, or unacceptable angina despite optimal medical therapy at baseline, so the study results don’t apply to them. Also, the acute kidney injury rate after intervention was eye-catchingly low.

Dr. Bangalore discussed the ISCHEMIA-CKD trial and outcomes in a video interview with Medscape’s Tricia Ward.

“It seems unlikely that all centers routinely do and will exactly follow the very careful measures to limit contrast and minimize contrast nephropathy used in this study,” Dr. Levine commented.

ISCHEMIA-CKD, like its parent ISCHEMIA trial, was funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore reported having no relevant financial interests. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire, which was used for quality of life measurement in the trials. Dr. Levine disclosed that he has no relations with industry or conflicts of interest.

bjancin@mdedge.com

PHILADELPHIA – Coronary revascularization in patients with stage 4 or 5 chronic kidney disease (CKD) and stable ischemic heart disease accomplishes nothing constructive, according to clear-cut results of the landmark ISCHEMIA-CKD trial.

In this multinational randomized trial including 777 stable patients with advanced CKD and moderate or severe myocardial ischemia on noninvasive testing, an early invasive strategy didn’t reduce the risks of death or ischemic events, didn’t provide any significant improvement in quality of life metrics, and resulted in an increased risk of stroke, Sripal Bangalore, MD, reported at the American Heart Association scientific sessions.

“Overall, an initial invasive strategy did not demonstrate a reduced risk of clinical outcomes as compared with an initial conservative strategy,” said Dr. Bangalore, professor of medicine and director of complex coronary intervention at New York University.

This was easily the largest-ever trial of an invasive versus conservative coronary artery disease management strategy in this challenging population. For example, in the COURAGE trial of optimal medical therapy with or without percutaneous coronary intervention for stable coronary disease (N Engl J Med. 2007 Apr 12;356[15]:1503-16), only 16 of the 2,287 participants had an estimated glomerular filtration rate below 30 mL/min per 1.73 m².

Of note, the participating study sites received special training aimed at minimizing the risk of acute kidney injury after cardiac catheterization in this at-risk population. The training included utilization of a customized left ventricular end diastolic volume–based hydration protocol, guidance on how to perform percutaneous coronary intervention with little or no contrast material, and encouragement of a heart/kidney team approach involving a cardiologist, nephrologist, and cardiovascular surgeon. This training really paid off, with roughly a 7% incidence of acute kidney injury after catheterization.

“The expected rate in such patients would be 30%-60%,” according to Dr. Bangalore.

The primary endpoint in ISCHEMIA-CKD was the rates of death or MI during 3 years of prospective follow-up. This occurred in 36.7% of patients randomized to optimal medical therapy alone and 36.4% of those randomized to an early invasive strategy. Similarly, the major secondary endpoint, comprising death, MI, and hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, was also a virtual dead heat, occurring in about 39% of subjects. More than 27% of study participants had died by the 3-year mark regardless of how their coronary disease was managed.

The adjusted risk of stroke was 3.76-fold higher in the invasive strategy group; however, the most strokes were not procedurally related, and the explanation for the significantly increased risk in the invasively managed group remains unknown, the cardiologist said.

John A. Spertus, MD, who led the quality of life assessment in ISCHEMIA-CKD and in the 5,129-patient parent ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), also presented at the AHA scientific sessions. He reported that, unlike in the parent study, there was no hint of a meaningful long-term quality of life benefit for revascularization plus optimal medical therapy, compared with that of optimal medical therapy alone, in ISCHEMIA-CKD.

“We have greater than 93% confidence that there is more of a quality of life effect in patients without advanced CKD than in patients with advanced CKD,” said Dr. Spertus, director of health outcomes research at the Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri, Kansas City.

Discussant Glenn L. Levine, MD, hailed ISCHEMIA-CKD as “a monumental achievement,” an ambitious, well-powered study with essentially no loss of follow-up during up to 4 years. It helps fill an utter void in the AHA/American College of Cardiology guidelines, which to date offer no recommendations at all regarding revascularization in patients with CKD because of a lack of evidence. And he considers ISCHEMIA-CKD to be unequivocally practice changing and guideline changing.

“Based on the results of ISCHEMIA-CKD, I will generally not go searching for ischemia and [coronary artery disease] in most severe and end-stage CKD patients, absent marked or unacceptable angina, and will treat them with medical therapy alone,” declared Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center, both in Houston.

He offered a few caveats. Excluded from participation in ISCHEMIA-CKD were patients with acute coronary syndrome, significant heart failure, or unacceptable angina despite optimal medical therapy at baseline, so the study results don’t apply to them. Also, the acute kidney injury rate after intervention was eye-catchingly low.

Dr. Bangalore discussed the ISCHEMIA-CKD trial and outcomes in a video interview with Medscape’s Tricia Ward.

“It seems unlikely that all centers routinely do and will exactly follow the very careful measures to limit contrast and minimize contrast nephropathy used in this study,” Dr. Levine commented.

ISCHEMIA-CKD, like its parent ISCHEMIA trial, was funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore reported having no relevant financial interests. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire, which was used for quality of life measurement in the trials. Dr. Levine disclosed that he has no relations with industry or conflicts of interest.

bjancin@mdedge.com

MADRID – Interleukin-1 alpha has emerged as a novel and unexpected potential therapeutic target in atopic dermatitis (AD) on the basis of an encouraging phase 2, proof-of-concept study involving bermekimab, an investigational monoclonal antibody directed at that cytokine.

Bruce Jancin/MDedge News

The mechanism of benefit is unclear, although there are a number of plausible possibilities, all orbiting around the notion that AD is not only a Th2 immunity–mediated disease, but that Th1 immunity plays a role, too.

“The ultimate proof, as you will see, is that it works,” Alice B. Gottlieb, MD, PhD, observed in presenting the phase 2 study findings at the annual congress of the European Academy of Dermatology and Venereology.

Bermekimab is a monoclonal antibody cloned from human peripheral B lymphocytes. Sources of its target – IL-1 alpha – that are of therapeutic relevance include neutrophils, keratinocytes, platelets, and monocytes.

The study included 10 adults with moderate to severe AD who received a single subcutaneous injection of 200 mg of bermekimab and 28 who received 400 mg weekly for 8 weeks. Lumping together the various outcome measures employed in the study, the 400-mg dose was three times more effective than the 200-mg dose, a finding explainable by the 240% higher serum levels at 400 mg, according to Dr. Gottlieb, medical director of Mount Sinai Beth Israel Dermatology in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

This was a small, uncontrolled, proof-of-concept study; at this early stage, results painted a favorable picture of efficacy and safety. For example, scores on the Eczema Area and Severity Index dropped by a mean of 65% from baseline at week 4 of bermekimab at 400 mg/week and by 80% at week 8. Scoring Atopic Dermatitis scores dropped by about 55% at week 4 and by nearly 70% at 8 weeks. Scores on the 0-4 Investigator Global Assessment improved by 1.2 points at week 4 and 1.4 points by week 8. Dermatology Life Quality Index scores improved by a mean of 70% by week 8, at which point 61% of patients had a DLQI of 0-1, indicating that AD had no or only a slight impact on quality of life. Scores on the Hospital Anxiety and Depression Scale improved by about 45% at 4 weeks and 65% at 8 weeks.

At baseline, most patients rated their pain as 7 out of 10. By week 8, pain scores had dropped by an average of 80%, and 80% of patients experienced a 4-point drop or greater. Similarly, 80% of patients had at least a 4-point drop in their self-rated worst itch scores on a 0-10 scale. The greatest improvement in both pain and itch scores occurred in the first 4 weeks, after which further improvement continued, albeit at a slower rate.

Adverse events consisted of grade 2 wheezing in two patients, grade 1 nausea in two patients, and a 3% rate of mild injection-site reactions.

An audience member rose to comment: “This is really interesting data, and it goes against everything that we think about atopic dermatitis. But we know from allergic contact dermatitis that IL-1 is a very early signal coming out of keratinocytes. It almost makes you wonder whether that’s not a primary problem in atopic dermatitis that we haven’t realized – that the keratinocytes are under stress because of damage to the skin barrier or other functions, and by alleviating that stress by blocking IL-1, you block the progression into what we previously thought was an Th2-mediated disease, atopic dermatitis.”

“I was thinking that, too – that the keratinocytes could be playing a role in atopic dermatitis through IL-1,” Dr. Gottlieb replied.

She noted that her Mount Sinai colleague Emma Guttman-Yassky, MD, PhD, and coinvestigators have demonstrated that a monoclonal antibody that blocks IL-17C is effective in treating AD, and that IL-17C causes keratinocytes to release proinflammatory IL-1 alpha. High levels of IL-1 alpha have been shown to drive leukocyte recruitment into the skin, promote breakdown of the skin barrier through production of matrix metalloproteinase, stimulate itch by a direct effect on nerves, and cause leaky vascular endothelium.

A phase 2 study of bermekimab for treatment of AD enrolled the first patient in mid-November. In addition, Dr. Gottlieb has led a positive phase 2 study of the monoclonal antibody in patients with hidradenitis suppurativa, with a phase 3 trial in the works.

She reported receiving research funding from and serving as a consultant without personal compensation to XBiotech, which sponsored the AD and hidradenitis suppurativa studies. She has similar financial relationships with numerous pharmaceutical companies developing psoriasis medications.

bjancin@mdedge.com

MADRID – Interleukin-1 alpha has emerged as a novel and unexpected potential therapeutic target in atopic dermatitis (AD) on the basis of an encouraging phase 2, proof-of-concept study involving bermekimab, an investigational monoclonal antibody directed at that cytokine.

Bruce Jancin/MDedge News

The mechanism of benefit is unclear, although there are a number of plausible possibilities, all orbiting around the notion that AD is not only a Th2 immunity–mediated disease, but that Th1 immunity plays a role, too.

“The ultimate proof, as you will see, is that it works,” Alice B. Gottlieb, MD, PhD, observed in presenting the phase 2 study findings at the annual congress of the European Academy of Dermatology and Venereology.

Bermekimab is a monoclonal antibody cloned from human peripheral B lymphocytes. Sources of its target – IL-1 alpha – that are of therapeutic relevance include neutrophils, keratinocytes, platelets, and monocytes.

The study included 10 adults with moderate to severe AD who received a single subcutaneous injection of 200 mg of bermekimab and 28 who received 400 mg weekly for 8 weeks. Lumping together the various outcome measures employed in the study, the 400-mg dose was three times more effective than the 200-mg dose, a finding explainable by the 240% higher serum levels at 400 mg, according to Dr. Gottlieb, medical director of Mount Sinai Beth Israel Dermatology in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

This was a small, uncontrolled, proof-of-concept study; at this early stage, results painted a favorable picture of efficacy and safety. For example, scores on the Eczema Area and Severity Index dropped by a mean of 65% from baseline at week 4 of bermekimab at 400 mg/week and by 80% at week 8. Scoring Atopic Dermatitis scores dropped by about 55% at week 4 and by nearly 70% at 8 weeks. Scores on the 0-4 Investigator Global Assessment improved by 1.2 points at week 4 and 1.4 points by week 8. Dermatology Life Quality Index scores improved by a mean of 70% by week 8, at which point 61% of patients had a DLQI of 0-1, indicating that AD had no or only a slight impact on quality of life. Scores on the Hospital Anxiety and Depression Scale improved by about 45% at 4 weeks and 65% at 8 weeks.

At baseline, most patients rated their pain as 7 out of 10. By week 8, pain scores had dropped by an average of 80%, and 80% of patients experienced a 4-point drop or greater. Similarly, 80% of patients had at least a 4-point drop in their self-rated worst itch scores on a 0-10 scale. The greatest improvement in both pain and itch scores occurred in the first 4 weeks, after which further improvement continued, albeit at a slower rate.

Adverse events consisted of grade 2 wheezing in two patients, grade 1 nausea in two patients, and a 3% rate of mild injection-site reactions.

An audience member rose to comment: “This is really interesting data, and it goes against everything that we think about atopic dermatitis. But we know from allergic contact dermatitis that IL-1 is a very early signal coming out of keratinocytes. It almost makes you wonder whether that’s not a primary problem in atopic dermatitis that we haven’t realized – that the keratinocytes are under stress because of damage to the skin barrier or other functions, and by alleviating that stress by blocking IL-1, you block the progression into what we previously thought was an Th2-mediated disease, atopic dermatitis.”

“I was thinking that, too – that the keratinocytes could be playing a role in atopic dermatitis through IL-1,” Dr. Gottlieb replied.

She noted that her Mount Sinai colleague Emma Guttman-Yassky, MD, PhD, and coinvestigators have demonstrated that a monoclonal antibody that blocks IL-17C is effective in treating AD, and that IL-17C causes keratinocytes to release proinflammatory IL-1 alpha. High levels of IL-1 alpha have been shown to drive leukocyte recruitment into the skin, promote breakdown of the skin barrier through production of matrix metalloproteinase, stimulate itch by a direct effect on nerves, and cause leaky vascular endothelium.

A phase 2 study of bermekimab for treatment of AD enrolled the first patient in mid-November. In addition, Dr. Gottlieb has led a positive phase 2 study of the monoclonal antibody in patients with hidradenitis suppurativa, with a phase 3 trial in the works.

She reported receiving research funding from and serving as a consultant without personal compensation to XBiotech, which sponsored the AD and hidradenitis suppurativa studies. She has similar financial relationships with numerous pharmaceutical companies developing psoriasis medications.

bjancin@mdedge.com

MADRID – Interleukin-1 alpha has emerged as a novel and unexpected potential therapeutic target in atopic dermatitis (AD) on the basis of an encouraging phase 2, proof-of-concept study involving bermekimab, an investigational monoclonal antibody directed at that cytokine.

Bruce Jancin/MDedge News

The mechanism of benefit is unclear, although there are a number of plausible possibilities, all orbiting around the notion that AD is not only a Th2 immunity–mediated disease, but that Th1 immunity plays a role, too.

“The ultimate proof, as you will see, is that it works,” Alice B. Gottlieb, MD, PhD, observed in presenting the phase 2 study findings at the annual congress of the European Academy of Dermatology and Venereology.

Bermekimab is a monoclonal antibody cloned from human peripheral B lymphocytes. Sources of its target – IL-1 alpha – that are of therapeutic relevance include neutrophils, keratinocytes, platelets, and monocytes.

The study included 10 adults with moderate to severe AD who received a single subcutaneous injection of 200 mg of bermekimab and 28 who received 400 mg weekly for 8 weeks. Lumping together the various outcome measures employed in the study, the 400-mg dose was three times more effective than the 200-mg dose, a finding explainable by the 240% higher serum levels at 400 mg, according to Dr. Gottlieb, medical director of Mount Sinai Beth Israel Dermatology in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

This was a small, uncontrolled, proof-of-concept study; at this early stage, results painted a favorable picture of efficacy and safety. For example, scores on the Eczema Area and Severity Index dropped by a mean of 65% from baseline at week 4 of bermekimab at 400 mg/week and by 80% at week 8. Scoring Atopic Dermatitis scores dropped by about 55% at week 4 and by nearly 70% at 8 weeks. Scores on the 0-4 Investigator Global Assessment improved by 1.2 points at week 4 and 1.4 points by week 8. Dermatology Life Quality Index scores improved by a mean of 70% by week 8, at which point 61% of patients had a DLQI of 0-1, indicating that AD had no or only a slight impact on quality of life. Scores on the Hospital Anxiety and Depression Scale improved by about 45% at 4 weeks and 65% at 8 weeks.

At baseline, most patients rated their pain as 7 out of 10. By week 8, pain scores had dropped by an average of 80%, and 80% of patients experienced a 4-point drop or greater. Similarly, 80% of patients had at least a 4-point drop in their self-rated worst itch scores on a 0-10 scale. The greatest improvement in both pain and itch scores occurred in the first 4 weeks, after which further improvement continued, albeit at a slower rate.

Adverse events consisted of grade 2 wheezing in two patients, grade 1 nausea in two patients, and a 3% rate of mild injection-site reactions.

An audience member rose to comment: “This is really interesting data, and it goes against everything that we think about atopic dermatitis. But we know from allergic contact dermatitis that IL-1 is a very early signal coming out of keratinocytes. It almost makes you wonder whether that’s not a primary problem in atopic dermatitis that we haven’t realized – that the keratinocytes are under stress because of damage to the skin barrier or other functions, and by alleviating that stress by blocking IL-1, you block the progression into what we previously thought was an Th2-mediated disease, atopic dermatitis.”

“I was thinking that, too – that the keratinocytes could be playing a role in atopic dermatitis through IL-1,” Dr. Gottlieb replied.

She noted that her Mount Sinai colleague Emma Guttman-Yassky, MD, PhD, and coinvestigators have demonstrated that a monoclonal antibody that blocks IL-17C is effective in treating AD, and that IL-17C causes keratinocytes to release proinflammatory IL-1 alpha. High levels of IL-1 alpha have been shown to drive leukocyte recruitment into the skin, promote breakdown of the skin barrier through production of matrix metalloproteinase, stimulate itch by a direct effect on nerves, and cause leaky vascular endothelium.

A phase 2 study of bermekimab for treatment of AD enrolled the first patient in mid-November. In addition, Dr. Gottlieb has led a positive phase 2 study of the monoclonal antibody in patients with hidradenitis suppurativa, with a phase 3 trial in the works.

She reported receiving research funding from and serving as a consultant without personal compensation to XBiotech, which sponsored the AD and hidradenitis suppurativa studies. She has similar financial relationships with numerous pharmaceutical companies developing psoriasis medications.

bjancin@mdedge.com

VANCOUVER, B.C. – Marijuana and cannabidiol (CBD) use is quite common among patients with pelvic pain resulting from endometriosis, with over a third reporting either current or past use, according to a new survey.

VladK213/Getty Images

The finding comes as more and more companies are marketing CBD-containing products to women, with unsubstantiated claims about efficacy, according to Anna Reinert, MD, who presented the research at a meeting sponsored by AAGL.

Women self-reported that marijuana use was moderately effective, while the median value for CBD corresponded to “slightly effective.”

To investigate use patterns, Dr. Reinert and colleagues created a questionnaire with 55-75 questions, which followed a branching logic tree. Topics included pain history, demographics, and experience with marijuana and CBD for the purpose of controlling pelvic pain. The survey was sent to two populations: an endometriosis association mailing list, and patients at a chronic pain center in Phoenix.

About 24,500 surveys were sent out; 366 were received and analyzed. The response rate was much different between the two populations, at 1% in the endometriosis association and 16% of the clinic population. Dr. Reinert attributed the low response rate in the association sample to the continuing stigma surrounding marijuana use, citing much higher response rates to other surveys sent out by the association around the same time.

Overall, 63% of respondents said they had never used marijuana; 37% reported past or present use; 65% said they had never used CBD; and 35% reported past or present use. About 45% of marijuana users reported that its use was very effective, and 25% said it was moderately effective. About 22% of CBD users said it was very effective, and about 33% said it was moderately effective. The median values lay in the moderately effective range for marijuana, and in the slightly effective range for CBD.

The findings suggest a need for more research into the potential benefit and limitations of cannabis for pelvic pain from endometriosis, said Dr. Reinert, an obstetrician/gynecologist the University of Southern California, Los Angeles.

Until this study, evidence of efficacy of marijuana for this indication has been sparse. A report from the National Academy of Sciences showed that there is evidence that cannabis and cannabinoids have a therapeutic effect on chronic pain in adults (National Academies Press (US) 2017 Jan 12), but the report made no mention of gynecological applications. Despite this lack of evidence, surveys have shown that women of reproductive age use marijuana, and an analysis by the Ameritox Laboratory in a pain management population found that 13% of women and 19% of men tested positive for marijuana in their urine.

Still, “there is not research looking at marijuana for women with chronic health pain,” Dr. Reinert said at the meeting.

But that doesn’t stop companies from developing CBD vaginal suppositories and marketing them for menstrual pelvic discomfort, pain during sex, and other issues. Lay press articles often boost these claims, although some skeptical takes address the lack of evidence. Still, “there’s a lot on the more positive side,” she said.

That leads to a lot of interest among patients in using marijuana or CBD for symptom relief, which is part of the reason that Dr. Reinert’s team decided to examine its use and perceived efficacy. Another reason is that there is some biological basis to believe that cannabis could be helpful. There is some evidence that women with endometriosis have changes in their endocannabinoid system (Cannabis Cannabinoid Res. 2017;2:72-80), and there are clinical trials examining the impact of non-CBD, non-tetrahydrocannabinol (THC) endocannabinoid ligands.

Dr. Reinert has no financial disclosures.

VANCOUVER, B.C. – Marijuana and cannabidiol (CBD) use is quite common among patients with pelvic pain resulting from endometriosis, with over a third reporting either current or past use, according to a new survey.

VladK213/Getty Images

The finding comes as more and more companies are marketing CBD-containing products to women, with unsubstantiated claims about efficacy, according to Anna Reinert, MD, who presented the research at a meeting sponsored by AAGL.

Women self-reported that marijuana use was moderately effective, while the median value for CBD corresponded to “slightly effective.”

To investigate use patterns, Dr. Reinert and colleagues created a questionnaire with 55-75 questions, which followed a branching logic tree. Topics included pain history, demographics, and experience with marijuana and CBD for the purpose of controlling pelvic pain. The survey was sent to two populations: an endometriosis association mailing list, and patients at a chronic pain center in Phoenix.

About 24,500 surveys were sent out; 366 were received and analyzed. The response rate was much different between the two populations, at 1% in the endometriosis association and 16% of the clinic population. Dr. Reinert attributed the low response rate in the association sample to the continuing stigma surrounding marijuana use, citing much higher response rates to other surveys sent out by the association around the same time.

Overall, 63% of respondents said they had never used marijuana; 37% reported past or present use; 65% said they had never used CBD; and 35% reported past or present use. About 45% of marijuana users reported that its use was very effective, and 25% said it was moderately effective. About 22% of CBD users said it was very effective, and about 33% said it was moderately effective. The median values lay in the moderately effective range for marijuana, and in the slightly effective range for CBD.

The findings suggest a need for more research into the potential benefit and limitations of cannabis for pelvic pain from endometriosis, said Dr. Reinert, an obstetrician/gynecologist the University of Southern California, Los Angeles.

Until this study, evidence of efficacy of marijuana for this indication has been sparse. A report from the National Academy of Sciences showed that there is evidence that cannabis and cannabinoids have a therapeutic effect on chronic pain in adults (National Academies Press (US) 2017 Jan 12), but the report made no mention of gynecological applications. Despite this lack of evidence, surveys have shown that women of reproductive age use marijuana, and an analysis by the Ameritox Laboratory in a pain management population found that 13% of women and 19% of men tested positive for marijuana in their urine.

Still, “there is not research looking at marijuana for women with chronic health pain,” Dr. Reinert said at the meeting.

But that doesn’t stop companies from developing CBD vaginal suppositories and marketing them for menstrual pelvic discomfort, pain during sex, and other issues. Lay press articles often boost these claims, although some skeptical takes address the lack of evidence. Still, “there’s a lot on the more positive side,” she said.

That leads to a lot of interest among patients in using marijuana or CBD for symptom relief, which is part of the reason that Dr. Reinert’s team decided to examine its use and perceived efficacy. Another reason is that there is some biological basis to believe that cannabis could be helpful. There is some evidence that women with endometriosis have changes in their endocannabinoid system (Cannabis Cannabinoid Res. 2017;2:72-80), and there are clinical trials examining the impact of non-CBD, non-tetrahydrocannabinol (THC) endocannabinoid ligands.

Dr. Reinert has no financial disclosures.

VANCOUVER, B.C. – Marijuana and cannabidiol (CBD) use is quite common among patients with pelvic pain resulting from endometriosis, with over a third reporting either current or past use, according to a new survey.

VladK213/Getty Images

The finding comes as more and more companies are marketing CBD-containing products to women, with unsubstantiated claims about efficacy, according to Anna Reinert, MD, who presented the research at a meeting sponsored by AAGL.

Women self-reported that marijuana use was moderately effective, while the median value for CBD corresponded to “slightly effective.”

To investigate use patterns, Dr. Reinert and colleagues created a questionnaire with 55-75 questions, which followed a branching logic tree. Topics included pain history, demographics, and experience with marijuana and CBD for the purpose of controlling pelvic pain. The survey was sent to two populations: an endometriosis association mailing list, and patients at a chronic pain center in Phoenix.

About 24,500 surveys were sent out; 366 were received and analyzed. The response rate was much different between the two populations, at 1% in the endometriosis association and 16% of the clinic population. Dr. Reinert attributed the low response rate in the association sample to the continuing stigma surrounding marijuana use, citing much higher response rates to other surveys sent out by the association around the same time.

Overall, 63% of respondents said they had never used marijuana; 37% reported past or present use; 65% said they had never used CBD; and 35% reported past or present use. About 45% of marijuana users reported that its use was very effective, and 25% said it was moderately effective. About 22% of CBD users said it was very effective, and about 33% said it was moderately effective. The median values lay in the moderately effective range for marijuana, and in the slightly effective range for CBD.

The findings suggest a need for more research into the potential benefit and limitations of cannabis for pelvic pain from endometriosis, said Dr. Reinert, an obstetrician/gynecologist the University of Southern California, Los Angeles.

Until this study, evidence of efficacy of marijuana for this indication has been sparse. A report from the National Academy of Sciences showed that there is evidence that cannabis and cannabinoids have a therapeutic effect on chronic pain in adults (National Academies Press (US) 2017 Jan 12), but the report made no mention of gynecological applications. Despite this lack of evidence, surveys have shown that women of reproductive age use marijuana, and an analysis by the Ameritox Laboratory in a pain management population found that 13% of women and 19% of men tested positive for marijuana in their urine.

Still, “there is not research looking at marijuana for women with chronic health pain,” Dr. Reinert said at the meeting.

But that doesn’t stop companies from developing CBD vaginal suppositories and marketing them for menstrual pelvic discomfort, pain during sex, and other issues. Lay press articles often boost these claims, although some skeptical takes address the lack of evidence. Still, “there’s a lot on the more positive side,” she said.

That leads to a lot of interest among patients in using marijuana or CBD for symptom relief, which is part of the reason that Dr. Reinert’s team decided to examine its use and perceived efficacy. Another reason is that there is some biological basis to believe that cannabis could be helpful. There is some evidence that women with endometriosis have changes in their endocannabinoid system (Cannabis Cannabinoid Res. 2017;2:72-80), and there are clinical trials examining the impact of non-CBD, non-tetrahydrocannabinol (THC) endocannabinoid ligands.

Dr. Reinert has no financial disclosures.