Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

A version of this article first appeared on Medscape.com.

Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

A version of this article first appeared on Medscape.com.

Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

A version of this article first appeared on Medscape.com.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

A new retrospective study provides more evidence that previous breast cancer diagnoses don’t disrupt the health of mothers and newborns in pregnancy: Women who became pregnant at least 12 months after breast cancer diagnosis weren’t more likely than a control group to have preterm births or suffer maternal/neonatal morbidity – even though they were more likely to undergo cesarean section.

“For patients who are more than 1 year out from the diagnosis of breast cancer, it may be safe and reasonable to consider pregnancy without significantly increased odds of maternal or neonatal complications,” said study lead author Kirsten Jorgensen, MD, a gynecologic oncology fellow at the University of Texas Houston School of Public Health, in an interview. “This study does not suggest there is no risk, but it does place the risk that exists in context with the risk that is associated with any pregnancy.”

The study appears in Obstetrics & Gynecology.

The researchers launched the analysis because “there is relatively little data to help guide patients, their oncologists, and their obstetricians as they navigate the potential for pregnancy after a cancer diagnosis,” Dr. Jorgensen said. “There have been prior studies looking at birth outcomes, but they often include people who become pregnant very shortly after diagnosis, which may skew results.”

Researchers used databases to track 30,021 women in California aged 18-45 who were diagnosed with breast cancer from 2000 to 2012. Of those, only 553 met the study criteria and conceived at least 1 year after a stage I-III breast cancer diagnosis (median age at delivery = 36; 50.6% non-Hispanic White, 23.9% Hispanic, 6.0% Black; 83.2% private insurance).

Study authors compared these women to a matched control group of 1,659 women without breast cancer.

After adjustment for various factors, there was no significant difference between the groups in terms of maternal outcomes – preterm birth at less than 37 weeks of gestation (12.5% in the breast cancer group vs. 10.0% in the control group; odds ratio = 1.29; 95% confidence interval, 0.95-1.74) or preterm birth at less than 32 weeks of gestation (1.3% vs. 1.6%, respectively, OR = 0.77; 95% CI, 0.34-1.79).

Researchers didn’t find a significant difference in neonatal outcomes either – small for gestational age (less than the 5th percentile, 3.1% vs. 5.0%, respectively; OR = 0.60, 95% CI, 0.35-1.03; less than the 10th percentile: 9.4% vs. 10%, respectively; OR = 0.94; 95% CI, 0.68-1.30), or neonatal morbidity (8.7% vs. 7.7%, respectively; OR = 1.15; 95% CI, 0.81-1.62).

“It is possible that breast cancer may have little impact because some breast cancer is treated only with surgery or radiation to the chest,” Dr. Jorgensen said. “These treatments likely do not impact fertility and may not impact a developing pregnancy.”

There were neonatal deaths: one in the breast cancer group and four in the control group. The researchers said the small number of deaths limited their ability to interpret the data.

Researchers found no evidence that treatment with chemotherapy affected outcomes. They did turn up a difference between the groups: those who’d had breast cancer were more likely to undergo cesarean delivery (45.6% in the breast cancer group, and 40.1% in the control group; OR = 1.25; 95% CI 1.03-1.53), However, offspring of women in the cesarean group weren’t more likely to have neonatal morbidity (OR = 1.15; 95% CI 0.81-1.62).

It’s hard to explain the higher rate of cesarean deliveries in the breast cancer group, Dr. Jorgensen said. “Overall, among our study population and the matched controls there was a high rate of cesarean section. It is possible there was bias on the provider side. Perhaps they intervened with cesarean section earlier among those with a history of breast cancer – a type of bias due to knowing the history of the patient. We attempted to match for other comorbidities that impact obstetric outcomes, but it is possible that we did not account for all of them.”

In an interview, Patricia A. Ganz, MD, director of cancer prevention and control research at University of California, Los Angeles, praised the new research.

It’s “a well-conducted study with state-of-the-art analysis and interpretation,” she said. “Based on my experience with patients I have cared for with breast cancer, there were no surprises here. Most have had uncomplicated pregnancies. This should be reassuring for women who wish to have children after treatment for breast cancer and clinicians should support this decision.”

As for the higher rate of cesarean delivery in breast-cancer survivors, she said “there may be a tendency to think of these as ‘high risk’ pregnancies, and C-sections may be selected at a more frequent rate as a result.”

The study was funded by the National Institutes of Health, including grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. Dr. Jorgensen has no disclosures. Other authors disclosed advisory board service (Delfina Care) and payments from the NIH, Guidepoint, the Schlesinger Group, and Johnson & Johnson. Dr. Ganz has no disclosures.

The spotlight continues to shine on vitiligo as Lego has released the first-ever mini-character featuring the hallmark dark and light skin patches of the disease.

The character appears with the customizable array of players to assemble for a table football team.

It’s the latest representation of the disease as toymakers diversify their lines.

In May 2022, Mattel released a Ken doll with vitiligo after a Barbie with vitiligo was released in 2020. Rainbow High and other toy makers also have character versions.

The Lego addition follows a big summer medically for vitiligo as the first treatment was approved for repigmentation. In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase inhibitor, became the first repigmentation treatment approved by the Food and Drug Administration for nonsegmental vitiligo, the most common form of the disease.

Vitiligo is estimated to affect 1.9 million–2.8 million adults in the United States and more than 100 million people worldwide. It cuts across races and genders and can be psychologically painful for many who live with it.

John E. Harris, MD, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester, wrote about the Lego character in his blog “Speaking of Vitiligo ...” saying: “I could not be more excited. This new minifigure also serves as a way to educate both children and adults who are not familiar with vitiligo about the disease.”

He noted that until recently vitiligo representation in kids’ toys has been limited. “By adding diversity such as representations of vitiligo in toys, it can help remove stigmas associated with vitiligo and give children more options that they can relate to.”

Erika Page of Richmond, Va., who founded and edits the vitiligo blog “Living Dappled,” told this news organization she was thrilled to see the new Lego character.

“Growing up I didn’t know anyone who looked like me, let alone a toy or a character,” she said. The message the representations send is important not just for the kids but for the parents of kids with vitiligo who want to help their kids in any way they can.

Ms. Page was diagnosed with vitiligo at age 7 and struggled emotionally in her high school and college years when she often looked in the mirror, saw “giraffe-like” spots, and cried. Over time she lost 100% of her pigment to the condition and today at age 33, lives with universal vitiligo or overall very pale skin.

She founded the Living Dappled blog 6 years ago to help people with the disease feel less alone. The Lego character will also help with that, she said.

“Growing up with vitiligo was so isolating and you felt so different,” Ms. Page said. “Today we see billboards and models and dolls and now Legos that look like us. I hope this is a first of many to come for Lego.”

Dr. Harris and Ms. Page declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The spotlight continues to shine on vitiligo as Lego has released the first-ever mini-character featuring the hallmark dark and light skin patches of the disease.

The character appears with the customizable array of players to assemble for a table football team.

It’s the latest representation of the disease as toymakers diversify their lines.

In May 2022, Mattel released a Ken doll with vitiligo after a Barbie with vitiligo was released in 2020. Rainbow High and other toy makers also have character versions.

The Lego addition follows a big summer medically for vitiligo as the first treatment was approved for repigmentation. In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase inhibitor, became the first repigmentation treatment approved by the Food and Drug Administration for nonsegmental vitiligo, the most common form of the disease.

Vitiligo is estimated to affect 1.9 million–2.8 million adults in the United States and more than 100 million people worldwide. It cuts across races and genders and can be psychologically painful for many who live with it.

John E. Harris, MD, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester, wrote about the Lego character in his blog “Speaking of Vitiligo ...” saying: “I could not be more excited. This new minifigure also serves as a way to educate both children and adults who are not familiar with vitiligo about the disease.”

He noted that until recently vitiligo representation in kids’ toys has been limited. “By adding diversity such as representations of vitiligo in toys, it can help remove stigmas associated with vitiligo and give children more options that they can relate to.”

Erika Page of Richmond, Va., who founded and edits the vitiligo blog “Living Dappled,” told this news organization she was thrilled to see the new Lego character.

“Growing up I didn’t know anyone who looked like me, let alone a toy or a character,” she said. The message the representations send is important not just for the kids but for the parents of kids with vitiligo who want to help their kids in any way they can.

Ms. Page was diagnosed with vitiligo at age 7 and struggled emotionally in her high school and college years when she often looked in the mirror, saw “giraffe-like” spots, and cried. Over time she lost 100% of her pigment to the condition and today at age 33, lives with universal vitiligo or overall very pale skin.

She founded the Living Dappled blog 6 years ago to help people with the disease feel less alone. The Lego character will also help with that, she said.

“Growing up with vitiligo was so isolating and you felt so different,” Ms. Page said. “Today we see billboards and models and dolls and now Legos that look like us. I hope this is a first of many to come for Lego.”

Dr. Harris and Ms. Page declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The spotlight continues to shine on vitiligo as Lego has released the first-ever mini-character featuring the hallmark dark and light skin patches of the disease.

The character appears with the customizable array of players to assemble for a table football team.

It’s the latest representation of the disease as toymakers diversify their lines.

In May 2022, Mattel released a Ken doll with vitiligo after a Barbie with vitiligo was released in 2020. Rainbow High and other toy makers also have character versions.

The Lego addition follows a big summer medically for vitiligo as the first treatment was approved for repigmentation. In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase inhibitor, became the first repigmentation treatment approved by the Food and Drug Administration for nonsegmental vitiligo, the most common form of the disease.

Vitiligo is estimated to affect 1.9 million–2.8 million adults in the United States and more than 100 million people worldwide. It cuts across races and genders and can be psychologically painful for many who live with it.

John E. Harris, MD, director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester, wrote about the Lego character in his blog “Speaking of Vitiligo ...” saying: “I could not be more excited. This new minifigure also serves as a way to educate both children and adults who are not familiar with vitiligo about the disease.”

He noted that until recently vitiligo representation in kids’ toys has been limited. “By adding diversity such as representations of vitiligo in toys, it can help remove stigmas associated with vitiligo and give children more options that they can relate to.”

Erika Page of Richmond, Va., who founded and edits the vitiligo blog “Living Dappled,” told this news organization she was thrilled to see the new Lego character.

“Growing up I didn’t know anyone who looked like me, let alone a toy or a character,” she said. The message the representations send is important not just for the kids but for the parents of kids with vitiligo who want to help their kids in any way they can.

Ms. Page was diagnosed with vitiligo at age 7 and struggled emotionally in her high school and college years when she often looked in the mirror, saw “giraffe-like” spots, and cried. Over time she lost 100% of her pigment to the condition and today at age 33, lives with universal vitiligo or overall very pale skin.

She founded the Living Dappled blog 6 years ago to help people with the disease feel less alone. The Lego character will also help with that, she said.

“Growing up with vitiligo was so isolating and you felt so different,” Ms. Page said. “Today we see billboards and models and dolls and now Legos that look like us. I hope this is a first of many to come for Lego.”

Dr. Harris and Ms. Page declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During screening colonoscopy, a scope withdrawal time (WT) of 9 minutes versus 6 minutes led to a reduced adenoma miss rate (AMR) and advanced adenoma miss rate (AAMR) and an improved adenoma detection rate (ADR), according to a randomized controlled trial conducted in China.

“Individual colonoscopists may acquire significant benefits in the ADR, AMR, AAMR, and high-risk adenoma miss rate from a 3-minute WT prolongation without compromising detection efficiency,” Zhao-Shen Li, MD, PhD, director, department of gastroenterology, Changhai Hospital and Second Military Medical University, Shanghai, said in an interview.

Based on evidence to date, the 9-minute WT “deserves to be considered as a new quality indicator to further optimize colonoscopy quality,” Dr. Li added.

The study is published online in the American Journal of Gastroenterology.

“This study certainly supports the notion that lengthening the examination time during colonoscopy results in more adenomas being detected,” Ziad F. Gellad, MD, who wasn’t involved in the study, told this news organization.

“When linking that with other studies showing a positive correlation between adenoma detection rate and interval cancers, we can conjecture that these longer exams will result in improved cancer detection. This makes intuitive sense,” said Dr. Gellad, associate professor of medicine, Duke University Medical Center, Durham, N.C.

In an earlier study, Dr. Li and colleagues found that prolonging the WT from a mean of 6 minutes to 9 minutes significantly improved the ADR (27.1% vs. 36.6%, P = .001).

Their latest study involved 733 asymptomatic adults aged 40-75 years undergoing screening colonoscopy by 15 gastroenterologists at 11 tertiary hospitals in China.

Participants were randomly allocated to segmental tandem screening colonoscopy with 9-minute withdrawal first (9MF) followed by 6-minute withdrawal (6MF) or vice versa.

In an intention-to-treat analysis, compared with 6MF, 9MF significantly reduced the lesion-level AMR (14.5% vs. 36.6%, P < .001), which was the primary outcome, and the participant-level AMR (10.9% vs. 25.9%; P < .001).

The 9MF also significantly reduced the AAMR (5.3% vs. 46.9%, P = .002), multiple AMR (20.7% vs. 56.5%; P = .01), and high-risk AMR (14.6% vs. 39.5%; P = .01) – without compromising detection efficiency.

The longer withdrawal time was also associated with a lower false-negative rate for adenomas (5.2% vs. 11.7%; P = .002) and high-risk adenomas (2.2% vs. 5%; P < .05), as well as a lower rate of shortening the surveillance schedule (P < .001).

A 9-minute mean WT also led to an improved ADR (42.3% vs. 33.5%, P = .02). The ADR improvement was associated with diminutive (P = .01), flat (P = .01), and tubular adenomas (P = .02).

Notably, colonoscopists with high ADRs (≥ 25%) in routine practice also showed a tendency of ADR improvement through a 3-minute prolongation (41% vs. 34.8%; P for interaction = .62), the investigators wrote.

Dr. Gellad said in an interview the study “reinforces the importance of careful inspection of the colonic mucosa during colonoscopy withdrawal. This should take as long as it takes to do it right, and that will vary by patient and by endoscopist.”

“Measurement of withdrawal time is helpful for quality improvement purposes when physician detection rates or miss rates are below goal,” Dr. Gellad added, “but timing the withdrawal should not be a goal in and of itself,”

The study was supported by the National Science and Technology Plan Project of the Ministry of Science and Technology of China. The authors reported no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and a cofounder of Higgs Boson.

A version of this article first appeared on Medscape.com.

During screening colonoscopy, a scope withdrawal time (WT) of 9 minutes versus 6 minutes led to a reduced adenoma miss rate (AMR) and advanced adenoma miss rate (AAMR) and an improved adenoma detection rate (ADR), according to a randomized controlled trial conducted in China.

“Individual colonoscopists may acquire significant benefits in the ADR, AMR, AAMR, and high-risk adenoma miss rate from a 3-minute WT prolongation without compromising detection efficiency,” Zhao-Shen Li, MD, PhD, director, department of gastroenterology, Changhai Hospital and Second Military Medical University, Shanghai, said in an interview.

Based on evidence to date, the 9-minute WT “deserves to be considered as a new quality indicator to further optimize colonoscopy quality,” Dr. Li added.

The study is published online in the American Journal of Gastroenterology.

“This study certainly supports the notion that lengthening the examination time during colonoscopy results in more adenomas being detected,” Ziad F. Gellad, MD, who wasn’t involved in the study, told this news organization.

“When linking that with other studies showing a positive correlation between adenoma detection rate and interval cancers, we can conjecture that these longer exams will result in improved cancer detection. This makes intuitive sense,” said Dr. Gellad, associate professor of medicine, Duke University Medical Center, Durham, N.C.

In an earlier study, Dr. Li and colleagues found that prolonging the WT from a mean of 6 minutes to 9 minutes significantly improved the ADR (27.1% vs. 36.6%, P = .001).

Their latest study involved 733 asymptomatic adults aged 40-75 years undergoing screening colonoscopy by 15 gastroenterologists at 11 tertiary hospitals in China.

Participants were randomly allocated to segmental tandem screening colonoscopy with 9-minute withdrawal first (9MF) followed by 6-minute withdrawal (6MF) or vice versa.

In an intention-to-treat analysis, compared with 6MF, 9MF significantly reduced the lesion-level AMR (14.5% vs. 36.6%, P < .001), which was the primary outcome, and the participant-level AMR (10.9% vs. 25.9%; P < .001).

The 9MF also significantly reduced the AAMR (5.3% vs. 46.9%, P = .002), multiple AMR (20.7% vs. 56.5%; P = .01), and high-risk AMR (14.6% vs. 39.5%; P = .01) – without compromising detection efficiency.

The longer withdrawal time was also associated with a lower false-negative rate for adenomas (5.2% vs. 11.7%; P = .002) and high-risk adenomas (2.2% vs. 5%; P < .05), as well as a lower rate of shortening the surveillance schedule (P < .001).

A 9-minute mean WT also led to an improved ADR (42.3% vs. 33.5%, P = .02). The ADR improvement was associated with diminutive (P = .01), flat (P = .01), and tubular adenomas (P = .02).

Notably, colonoscopists with high ADRs (≥ 25%) in routine practice also showed a tendency of ADR improvement through a 3-minute prolongation (41% vs. 34.8%; P for interaction = .62), the investigators wrote.

Dr. Gellad said in an interview the study “reinforces the importance of careful inspection of the colonic mucosa during colonoscopy withdrawal. This should take as long as it takes to do it right, and that will vary by patient and by endoscopist.”

“Measurement of withdrawal time is helpful for quality improvement purposes when physician detection rates or miss rates are below goal,” Dr. Gellad added, “but timing the withdrawal should not be a goal in and of itself,”

The study was supported by the National Science and Technology Plan Project of the Ministry of Science and Technology of China. The authors reported no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and a cofounder of Higgs Boson.

A version of this article first appeared on Medscape.com.

During screening colonoscopy, a scope withdrawal time (WT) of 9 minutes versus 6 minutes led to a reduced adenoma miss rate (AMR) and advanced adenoma miss rate (AAMR) and an improved adenoma detection rate (ADR), according to a randomized controlled trial conducted in China.

“Individual colonoscopists may acquire significant benefits in the ADR, AMR, AAMR, and high-risk adenoma miss rate from a 3-minute WT prolongation without compromising detection efficiency,” Zhao-Shen Li, MD, PhD, director, department of gastroenterology, Changhai Hospital and Second Military Medical University, Shanghai, said in an interview.

Based on evidence to date, the 9-minute WT “deserves to be considered as a new quality indicator to further optimize colonoscopy quality,” Dr. Li added.

The study is published online in the American Journal of Gastroenterology.

“This study certainly supports the notion that lengthening the examination time during colonoscopy results in more adenomas being detected,” Ziad F. Gellad, MD, who wasn’t involved in the study, told this news organization.

“When linking that with other studies showing a positive correlation between adenoma detection rate and interval cancers, we can conjecture that these longer exams will result in improved cancer detection. This makes intuitive sense,” said Dr. Gellad, associate professor of medicine, Duke University Medical Center, Durham, N.C.

In an earlier study, Dr. Li and colleagues found that prolonging the WT from a mean of 6 minutes to 9 minutes significantly improved the ADR (27.1% vs. 36.6%, P = .001).

Their latest study involved 733 asymptomatic adults aged 40-75 years undergoing screening colonoscopy by 15 gastroenterologists at 11 tertiary hospitals in China.

Participants were randomly allocated to segmental tandem screening colonoscopy with 9-minute withdrawal first (9MF) followed by 6-minute withdrawal (6MF) or vice versa.

In an intention-to-treat analysis, compared with 6MF, 9MF significantly reduced the lesion-level AMR (14.5% vs. 36.6%, P < .001), which was the primary outcome, and the participant-level AMR (10.9% vs. 25.9%; P < .001).

The 9MF also significantly reduced the AAMR (5.3% vs. 46.9%, P = .002), multiple AMR (20.7% vs. 56.5%; P = .01), and high-risk AMR (14.6% vs. 39.5%; P = .01) – without compromising detection efficiency.

The longer withdrawal time was also associated with a lower false-negative rate for adenomas (5.2% vs. 11.7%; P = .002) and high-risk adenomas (2.2% vs. 5%; P < .05), as well as a lower rate of shortening the surveillance schedule (P < .001).

A 9-minute mean WT also led to an improved ADR (42.3% vs. 33.5%, P = .02). The ADR improvement was associated with diminutive (P = .01), flat (P = .01), and tubular adenomas (P = .02).

Notably, colonoscopists with high ADRs (≥ 25%) in routine practice also showed a tendency of ADR improvement through a 3-minute prolongation (41% vs. 34.8%; P for interaction = .62), the investigators wrote.

Dr. Gellad said in an interview the study “reinforces the importance of careful inspection of the colonic mucosa during colonoscopy withdrawal. This should take as long as it takes to do it right, and that will vary by patient and by endoscopist.”

“Measurement of withdrawal time is helpful for quality improvement purposes when physician detection rates or miss rates are below goal,” Dr. Gellad added, “but timing the withdrawal should not be a goal in and of itself,”

The study was supported by the National Science and Technology Plan Project of the Ministry of Science and Technology of China. The authors reported no relevant financial relationships. Dr. Gellad is a consultant for Merck and Novo Nordisk and a cofounder of Higgs Boson.

A version of this article first appeared on Medscape.com.

There has been a steady decline in Medicare reimbursement for common gastrointestinal (GI) services and patient office visits over the past 15 years, which could have a direct impact on patients.

“When Medicare reimbursements decrease, health outcomes, health care access, and patient satisfaction may be affected, particularly in light of high inflation and increased costs due to staffing shortages, increased staffing salaries, and additional equipment necessary for COVID-19 safety,” researchers wrote in The American Journal of Gastroenterology.

Samir A. Shah, MD, of Brown University, Providence, R.I., and colleagues evaluated trends from 2007 to 2022 in Medicare reimbursement for the top 10 common GI procedures.

These procedures, which included colonoscopies, endoscopies, and gastrostomy tube placement, were identified through a joint list published by the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the American Gastroenterological Association.

From 2007 to 2022, unadjusted and adjusted reimbursement for GI procedures declined by 7% and 33%, respectively, on average.

The adjusted change in physician reimbursement ranged from a decrease of roughly 29% for esophagus endoscopy to 38% for colonoscopy and biopsy, the study team found.

They found that the decline in reimbursement of GI procedures was significantly larger after 2015 (P < .001).

From 2007 to 2014, the mean decrease in physician reimbursement for GI services was 6.7%, and the annual growth rate in reimbursement was –1.0%.

In comparison, from 2015 to 2022, the mean decrease in physician reimbursement was 28.2%, and the mean annual growth rate in reimbursement was –4.7%.

To examine trends in reimbursement for office and inpatient visits from 2007 to 2022, the researchers identified the top five current procedural terminology (CPT) codes from outpatient office and inpatient consult visits provided to Medicare Part B beneficiaries by gastroenterologists.

In contrast to the reimbursement trends for GI procedures, the unadjusted physician reimbursement for inpatient and outpatient visits showed an average increase of 32%.

However, after adjustment for inflation, physician reimbursement for patient visits showed an average decline of 4.9%.

Overall, reimbursement for outpatient visits increased by 4.3%, while reimbursement for inpatient visits decreased by 18.8%.

Dr. Shah and colleagues said their findings are important, given that Medicare patients make up a substantial and growing proportion of patients with GI problems and because fewer than 1% of gastroenterologists have opted out of Medicare.

They noted that the trends in GI reimbursement they observed mirror trends in other specialties, which have also noted a decrease in adjusted reimbursement for care.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There has been a steady decline in Medicare reimbursement for common gastrointestinal (GI) services and patient office visits over the past 15 years, which could have a direct impact on patients.

“When Medicare reimbursements decrease, health outcomes, health care access, and patient satisfaction may be affected, particularly in light of high inflation and increased costs due to staffing shortages, increased staffing salaries, and additional equipment necessary for COVID-19 safety,” researchers wrote in The American Journal of Gastroenterology.

Samir A. Shah, MD, of Brown University, Providence, R.I., and colleagues evaluated trends from 2007 to 2022 in Medicare reimbursement for the top 10 common GI procedures.

These procedures, which included colonoscopies, endoscopies, and gastrostomy tube placement, were identified through a joint list published by the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the American Gastroenterological Association.

From 2007 to 2022, unadjusted and adjusted reimbursement for GI procedures declined by 7% and 33%, respectively, on average.

The adjusted change in physician reimbursement ranged from a decrease of roughly 29% for esophagus endoscopy to 38% for colonoscopy and biopsy, the study team found.

They found that the decline in reimbursement of GI procedures was significantly larger after 2015 (P < .001).

From 2007 to 2014, the mean decrease in physician reimbursement for GI services was 6.7%, and the annual growth rate in reimbursement was –1.0%.

In comparison, from 2015 to 2022, the mean decrease in physician reimbursement was 28.2%, and the mean annual growth rate in reimbursement was –4.7%.

To examine trends in reimbursement for office and inpatient visits from 2007 to 2022, the researchers identified the top five current procedural terminology (CPT) codes from outpatient office and inpatient consult visits provided to Medicare Part B beneficiaries by gastroenterologists.

In contrast to the reimbursement trends for GI procedures, the unadjusted physician reimbursement for inpatient and outpatient visits showed an average increase of 32%.

However, after adjustment for inflation, physician reimbursement for patient visits showed an average decline of 4.9%.

Overall, reimbursement for outpatient visits increased by 4.3%, while reimbursement for inpatient visits decreased by 18.8%.

Dr. Shah and colleagues said their findings are important, given that Medicare patients make up a substantial and growing proportion of patients with GI problems and because fewer than 1% of gastroenterologists have opted out of Medicare.

They noted that the trends in GI reimbursement they observed mirror trends in other specialties, which have also noted a decrease in adjusted reimbursement for care.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There has been a steady decline in Medicare reimbursement for common gastrointestinal (GI) services and patient office visits over the past 15 years, which could have a direct impact on patients.

“When Medicare reimbursements decrease, health outcomes, health care access, and patient satisfaction may be affected, particularly in light of high inflation and increased costs due to staffing shortages, increased staffing salaries, and additional equipment necessary for COVID-19 safety,” researchers wrote in The American Journal of Gastroenterology.

Samir A. Shah, MD, of Brown University, Providence, R.I., and colleagues evaluated trends from 2007 to 2022 in Medicare reimbursement for the top 10 common GI procedures.

These procedures, which included colonoscopies, endoscopies, and gastrostomy tube placement, were identified through a joint list published by the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the American Gastroenterological Association.

From 2007 to 2022, unadjusted and adjusted reimbursement for GI procedures declined by 7% and 33%, respectively, on average.

The adjusted change in physician reimbursement ranged from a decrease of roughly 29% for esophagus endoscopy to 38% for colonoscopy and biopsy, the study team found.

They found that the decline in reimbursement of GI procedures was significantly larger after 2015 (P < .001).

From 2007 to 2014, the mean decrease in physician reimbursement for GI services was 6.7%, and the annual growth rate in reimbursement was –1.0%.

In comparison, from 2015 to 2022, the mean decrease in physician reimbursement was 28.2%, and the mean annual growth rate in reimbursement was –4.7%.

To examine trends in reimbursement for office and inpatient visits from 2007 to 2022, the researchers identified the top five current procedural terminology (CPT) codes from outpatient office and inpatient consult visits provided to Medicare Part B beneficiaries by gastroenterologists.

In contrast to the reimbursement trends for GI procedures, the unadjusted physician reimbursement for inpatient and outpatient visits showed an average increase of 32%.

However, after adjustment for inflation, physician reimbursement for patient visits showed an average decline of 4.9%.

Overall, reimbursement for outpatient visits increased by 4.3%, while reimbursement for inpatient visits decreased by 18.8%.

Dr. Shah and colleagues said their findings are important, given that Medicare patients make up a substantial and growing proportion of patients with GI problems and because fewer than 1% of gastroenterologists have opted out of Medicare.

They noted that the trends in GI reimbursement they observed mirror trends in other specialties, which have also noted a decrease in adjusted reimbursement for care.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

The incidence of new celiac disease with onset by age 10 appears to be rising and varies widely by region, suggesting different environmental, genetic, and epigenetic influences within the United States, according to a new report.

The overall high incidence among pediatric patients warrants a low threshold for screening and additional research on region-specific celiac disease triggers, the authors write.

“Determining the true incidence of celiac disease (CD) is not possible without nonbiased screening for the disease. This is because many cases occur with neither a family history nor with classic symptoms,” write Edwin Liu, MD, a pediatric gastroenterologist at the Children’s Hospital Colorado Anschutz Medical Campus and director of the Colorado Center for Celiac Disease, and colleagues.

“Individuals may have celiac disease autoimmunity without having CD if they have transient or fluctuating antibody levels, low antibody levels without biopsy evaluation, dietary modification influencing further evaluation, or potential celiac disease,” they write.

The study was published online in The American Journal of Gastroenterology.
 

Celiac disease incidence

The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows children born between 2004 and 2010 who are at genetic risk for both type 1 diabetes and CD at six clinical sites in four countries: the United States, Finland, Germany, and Sweden. In the United States, patients are enrolled in Colorado, Georgia, and Washington.

As part of TEDDY, children are longitudinally monitored for celiac disease autoimmunity (CDA) by assessment of autoantibodies to tissue transglutaminase (tTGA). The protocol is designed to analyze the development of persistent tTGA positivity, CDA, and subsequent CD. The study population contains various DQ2.5 and DQ8.1 combinations, which represent the highest-risk human leukocyte antigen (HLA) DQ haplogentotypes for CD.

From September 2004 through February 2010, more than 424,000 newborns were screened for specific HLA haplogenotypes, and 8,676 children were enrolled in TEDDY at the six clinical sites. The eligible haplogenotypes included DQ2.5/DQ2.5, DQ2.5/DQ8.1, DQ8.1/DQ8.1, and DQ8.1/DQ4.2.

Blood samples were obtained and stored every 3 months until age 48 months and at least every 6 months after that. At age 2, participants were screened annually for tTGA. With the first tTGA-positive result, all prior collected samples from the patient were tested for tTGA to determine the earliest time point of autoimmunity.

CDA, a primary study outcome, was defined as positivity in two consecutive tTGA tests at least 3 months apart.

In seropositive children, CD was defined on the basis of a duodenal biopsy with a Marsh score of 2 or higher. The decision to perform a biopsy was determined by the clinical gastroenterologist and was outside of the study protocol. When a biopsy wasn’t performed, participants with an average tTGA of 100 units or greater from two positive tests were considered to have CD for the study purposes.

As of July 2020, among the children who had undergone one or more tTGA tests, 6,628 HLA-typed eligible children were found to carry the DQ2.5, the D8.1, or both haplogenotypes and were included in the analysis. The median follow-up period was 11.5 years.

Overall, 580 children (9%) had a first-degree relative with type 1 diabetes, and 317 children (5%) reported a first-degree relative with CD.

Among the 6,628 children, 1,299 (20%) met the CDA outcome, and 529 (8%) met the study diagnostic criteria for CD on the basis of biopsy or persistently high tTGA levels. The median age at CDA across all sites was 41 months. Most children with CDA were asymptomatic.

Overall, the 10-year cumulative incidence was highest in Sweden, at 8.4% for CDA and 3% for CD. Within the United States, Colorado had the highest cumulative incidence for both endpoints, at 6.5% for CDA and 2.4% for CD. Washington had the lowest incidence across all sites, at 4.6% for CDA and 0.9% for CD.

“CDA and CD risk varied substantially by haplogenotype and by clinical center, but the relative risk by region was preserved regardless of the haplogenotype,” the authors write. “For example, the disease burden for each region remained highest in Sweden and lowest in Washington state for all haplogenotypes.”
 

Site-specific risks

In the HLA, sex, and family-adjusted model, Colorado children had a 2.5-fold higher risk of CD, compared with Washington children. Likewise, Swedish children had a 1.8-fold higher risk of CD than children in Germany, a 1.7-fold higher than children in the United States, and a 1.4-fold higher risk than children in Finland.

Among DQ2.5 participants, Sweden demonstrated the highest risk, with 63.1% of patients developing CDA by age 10 and 28.3% developing CD by age 10. Finland consistently had a higher incidence of CDA than Colorado, at 60.4% versus 50.9%, for DQ2.5 participants but a lower incidence of CD than Colorado, at 20.3% versus 22.6%.

The research team performed a post hoc sensitivity analysis using a lower tTGA cutoff to reduce bias in site differences for biopsy referral and to increase sensitivity of the CD definition for incidence estimation. When the tTGA cutoff was lowered to an average two-visit tTGA of 67.4 or higher, more children met the serologic criteria for CD.

“Even with this lower cutoff, the differences in the risk of CD between clinical sites and countries were still observed with statistical significance,” the authors write. “This indicates that the regional differences in CD incidence could not be solely attributed to detection biases posed by differential biopsy rates.”

Multiple environmental factors likely account for the differences in autoimmunity among regions, the authors write. These variables include diet, chemical exposures, vaccination patterns, early-life gastrointestinal infections, and interactions among these factors. For instance, the Swedish site has the lowest rotavirus vaccination rates and the highest median gluten intake among the TEDDY sites.

Future prospective studies should capture environmental, genetic, and epigenetic exposures to assess causal pathways and plan for preventive strategies, the authors write. The TEDDY study is pursuing this research.

“From a policy standpoint, this informs future screening practices and supports efforts toward mass screening, at least in some areas,” the authors write. “In the clinical setting, this points to the importance for clinicians to have a low threshold for CD screening in the appropriate clinical setting.”

The TEDDY study is funded by several grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the Juvenile Diabetes Research Foundation. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of new celiac disease with onset by age 10 appears to be rising and varies widely by region, suggesting different environmental, genetic, and epigenetic influences within the United States, according to a new report.

The overall high incidence among pediatric patients warrants a low threshold for screening and additional research on region-specific celiac disease triggers, the authors write.

“Determining the true incidence of celiac disease (CD) is not possible without nonbiased screening for the disease. This is because many cases occur with neither a family history nor with classic symptoms,” write Edwin Liu, MD, a pediatric gastroenterologist at the Children’s Hospital Colorado Anschutz Medical Campus and director of the Colorado Center for Celiac Disease, and colleagues.

“Individuals may have celiac disease autoimmunity without having CD if they have transient or fluctuating antibody levels, low antibody levels without biopsy evaluation, dietary modification influencing further evaluation, or potential celiac disease,” they write.

The study was published online in The American Journal of Gastroenterology.
 

Celiac disease incidence

The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows children born between 2004 and 2010 who are at genetic risk for both type 1 diabetes and CD at six clinical sites in four countries: the United States, Finland, Germany, and Sweden. In the United States, patients are enrolled in Colorado, Georgia, and Washington.

As part of TEDDY, children are longitudinally monitored for celiac disease autoimmunity (CDA) by assessment of autoantibodies to tissue transglutaminase (tTGA). The protocol is designed to analyze the development of persistent tTGA positivity, CDA, and subsequent CD. The study population contains various DQ2.5 and DQ8.1 combinations, which represent the highest-risk human leukocyte antigen (HLA) DQ haplogentotypes for CD.

From September 2004 through February 2010, more than 424,000 newborns were screened for specific HLA haplogenotypes, and 8,676 children were enrolled in TEDDY at the six clinical sites. The eligible haplogenotypes included DQ2.5/DQ2.5, DQ2.5/DQ8.1, DQ8.1/DQ8.1, and DQ8.1/DQ4.2.

Blood samples were obtained and stored every 3 months until age 48 months and at least every 6 months after that. At age 2, participants were screened annually for tTGA. With the first tTGA-positive result, all prior collected samples from the patient were tested for tTGA to determine the earliest time point of autoimmunity.

CDA, a primary study outcome, was defined as positivity in two consecutive tTGA tests at least 3 months apart.

In seropositive children, CD was defined on the basis of a duodenal biopsy with a Marsh score of 2 or higher. The decision to perform a biopsy was determined by the clinical gastroenterologist and was outside of the study protocol. When a biopsy wasn’t performed, participants with an average tTGA of 100 units or greater from two positive tests were considered to have CD for the study purposes.

As of July 2020, among the children who had undergone one or more tTGA tests, 6,628 HLA-typed eligible children were found to carry the DQ2.5, the D8.1, or both haplogenotypes and were included in the analysis. The median follow-up period was 11.5 years.

Overall, 580 children (9%) had a first-degree relative with type 1 diabetes, and 317 children (5%) reported a first-degree relative with CD.

Among the 6,628 children, 1,299 (20%) met the CDA outcome, and 529 (8%) met the study diagnostic criteria for CD on the basis of biopsy or persistently high tTGA levels. The median age at CDA across all sites was 41 months. Most children with CDA were asymptomatic.

Overall, the 10-year cumulative incidence was highest in Sweden, at 8.4% for CDA and 3% for CD. Within the United States, Colorado had the highest cumulative incidence for both endpoints, at 6.5% for CDA and 2.4% for CD. Washington had the lowest incidence across all sites, at 4.6% for CDA and 0.9% for CD.

“CDA and CD risk varied substantially by haplogenotype and by clinical center, but the relative risk by region was preserved regardless of the haplogenotype,” the authors write. “For example, the disease burden for each region remained highest in Sweden and lowest in Washington state for all haplogenotypes.”
 

Site-specific risks

In the HLA, sex, and family-adjusted model, Colorado children had a 2.5-fold higher risk of CD, compared with Washington children. Likewise, Swedish children had a 1.8-fold higher risk of CD than children in Germany, a 1.7-fold higher than children in the United States, and a 1.4-fold higher risk than children in Finland.

Among DQ2.5 participants, Sweden demonstrated the highest risk, with 63.1% of patients developing CDA by age 10 and 28.3% developing CD by age 10. Finland consistently had a higher incidence of CDA than Colorado, at 60.4% versus 50.9%, for DQ2.5 participants but a lower incidence of CD than Colorado, at 20.3% versus 22.6%.

The research team performed a post hoc sensitivity analysis using a lower tTGA cutoff to reduce bias in site differences for biopsy referral and to increase sensitivity of the CD definition for incidence estimation. When the tTGA cutoff was lowered to an average two-visit tTGA of 67.4 or higher, more children met the serologic criteria for CD.

“Even with this lower cutoff, the differences in the risk of CD between clinical sites and countries were still observed with statistical significance,” the authors write. “This indicates that the regional differences in CD incidence could not be solely attributed to detection biases posed by differential biopsy rates.”

Multiple environmental factors likely account for the differences in autoimmunity among regions, the authors write. These variables include diet, chemical exposures, vaccination patterns, early-life gastrointestinal infections, and interactions among these factors. For instance, the Swedish site has the lowest rotavirus vaccination rates and the highest median gluten intake among the TEDDY sites.

Future prospective studies should capture environmental, genetic, and epigenetic exposures to assess causal pathways and plan for preventive strategies, the authors write. The TEDDY study is pursuing this research.

“From a policy standpoint, this informs future screening practices and supports efforts toward mass screening, at least in some areas,” the authors write. “In the clinical setting, this points to the importance for clinicians to have a low threshold for CD screening in the appropriate clinical setting.”

The TEDDY study is funded by several grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the Juvenile Diabetes Research Foundation. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of new celiac disease with onset by age 10 appears to be rising and varies widely by region, suggesting different environmental, genetic, and epigenetic influences within the United States, according to a new report.

The overall high incidence among pediatric patients warrants a low threshold for screening and additional research on region-specific celiac disease triggers, the authors write.

“Determining the true incidence of celiac disease (CD) is not possible without nonbiased screening for the disease. This is because many cases occur with neither a family history nor with classic symptoms,” write Edwin Liu, MD, a pediatric gastroenterologist at the Children’s Hospital Colorado Anschutz Medical Campus and director of the Colorado Center for Celiac Disease, and colleagues.

“Individuals may have celiac disease autoimmunity without having CD if they have transient or fluctuating antibody levels, low antibody levels without biopsy evaluation, dietary modification influencing further evaluation, or potential celiac disease,” they write.

The study was published online in The American Journal of Gastroenterology.
 

Celiac disease incidence

The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows children born between 2004 and 2010 who are at genetic risk for both type 1 diabetes and CD at six clinical sites in four countries: the United States, Finland, Germany, and Sweden. In the United States, patients are enrolled in Colorado, Georgia, and Washington.

As part of TEDDY, children are longitudinally monitored for celiac disease autoimmunity (CDA) by assessment of autoantibodies to tissue transglutaminase (tTGA). The protocol is designed to analyze the development of persistent tTGA positivity, CDA, and subsequent CD. The study population contains various DQ2.5 and DQ8.1 combinations, which represent the highest-risk human leukocyte antigen (HLA) DQ haplogentotypes for CD.

From September 2004 through February 2010, more than 424,000 newborns were screened for specific HLA haplogenotypes, and 8,676 children were enrolled in TEDDY at the six clinical sites. The eligible haplogenotypes included DQ2.5/DQ2.5, DQ2.5/DQ8.1, DQ8.1/DQ8.1, and DQ8.1/DQ4.2.

Blood samples were obtained and stored every 3 months until age 48 months and at least every 6 months after that. At age 2, participants were screened annually for tTGA. With the first tTGA-positive result, all prior collected samples from the patient were tested for tTGA to determine the earliest time point of autoimmunity.

CDA, a primary study outcome, was defined as positivity in two consecutive tTGA tests at least 3 months apart.

In seropositive children, CD was defined on the basis of a duodenal biopsy with a Marsh score of 2 or higher. The decision to perform a biopsy was determined by the clinical gastroenterologist and was outside of the study protocol. When a biopsy wasn’t performed, participants with an average tTGA of 100 units or greater from two positive tests were considered to have CD for the study purposes.

As of July 2020, among the children who had undergone one or more tTGA tests, 6,628 HLA-typed eligible children were found to carry the DQ2.5, the D8.1, or both haplogenotypes and were included in the analysis. The median follow-up period was 11.5 years.

Overall, 580 children (9%) had a first-degree relative with type 1 diabetes, and 317 children (5%) reported a first-degree relative with CD.

Among the 6,628 children, 1,299 (20%) met the CDA outcome, and 529 (8%) met the study diagnostic criteria for CD on the basis of biopsy or persistently high tTGA levels. The median age at CDA across all sites was 41 months. Most children with CDA were asymptomatic.

Overall, the 10-year cumulative incidence was highest in Sweden, at 8.4% for CDA and 3% for CD. Within the United States, Colorado had the highest cumulative incidence for both endpoints, at 6.5% for CDA and 2.4% for CD. Washington had the lowest incidence across all sites, at 4.6% for CDA and 0.9% for CD.

“CDA and CD risk varied substantially by haplogenotype and by clinical center, but the relative risk by region was preserved regardless of the haplogenotype,” the authors write. “For example, the disease burden for each region remained highest in Sweden and lowest in Washington state for all haplogenotypes.”
 

Site-specific risks

In the HLA, sex, and family-adjusted model, Colorado children had a 2.5-fold higher risk of CD, compared with Washington children. Likewise, Swedish children had a 1.8-fold higher risk of CD than children in Germany, a 1.7-fold higher than children in the United States, and a 1.4-fold higher risk than children in Finland.

Among DQ2.5 participants, Sweden demonstrated the highest risk, with 63.1% of patients developing CDA by age 10 and 28.3% developing CD by age 10. Finland consistently had a higher incidence of CDA than Colorado, at 60.4% versus 50.9%, for DQ2.5 participants but a lower incidence of CD than Colorado, at 20.3% versus 22.6%.

The research team performed a post hoc sensitivity analysis using a lower tTGA cutoff to reduce bias in site differences for biopsy referral and to increase sensitivity of the CD definition for incidence estimation. When the tTGA cutoff was lowered to an average two-visit tTGA of 67.4 or higher, more children met the serologic criteria for CD.

“Even with this lower cutoff, the differences in the risk of CD between clinical sites and countries were still observed with statistical significance,” the authors write. “This indicates that the regional differences in CD incidence could not be solely attributed to detection biases posed by differential biopsy rates.”

Multiple environmental factors likely account for the differences in autoimmunity among regions, the authors write. These variables include diet, chemical exposures, vaccination patterns, early-life gastrointestinal infections, and interactions among these factors. For instance, the Swedish site has the lowest rotavirus vaccination rates and the highest median gluten intake among the TEDDY sites.

Future prospective studies should capture environmental, genetic, and epigenetic exposures to assess causal pathways and plan for preventive strategies, the authors write. The TEDDY study is pursuing this research.

“From a policy standpoint, this informs future screening practices and supports efforts toward mass screening, at least in some areas,” the authors write. “In the clinical setting, this points to the importance for clinicians to have a low threshold for CD screening in the appropriate clinical setting.”

The TEDDY study is funded by several grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the Juvenile Diabetes Research Foundation. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pulmonary Vascular Disease Section

Key messages from the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension

1. Per coverage by the American College of Cardiology, “Pulmonary hypertension (PH) is now defined by a mean pulmonary arterial pressure >20 mm Hg at rest. The definition of pulmonary arterial hypertension (PAH) also implies a pulmonary vascular resistance (PVR) >2 Wood units and pulmonary arterial wedge pressure ≤15 mm Hg.”¹ These cut-off values do not translate into new therapeutic recommendations.

2. The diagnostic algorithm for PH now follows a simplified three-step approach, involving first suspicion by first-line physicians, then detection by echocardiography, and confirmation with right heart catheterization, preferably in a PH center.

3. Pulmonary vasoreactivity testing is only recommended in patients with idiopathic PAH, heritable PAH, or drug/toxin associated PAH to identify potential candidates for calcium channel blocker therapy. Inhaled nitric oxide or inhaled iloprost are the recommended agents.

*Mary Jo S. Farmer, MD, PhD
 Member-at-Large

Vijay Balasubramanian, MD, MRCP (UK)
Chair
 

*  The authors for this article were listed in the incorrect order in the print edition of CHEST Physician. The order has been corrected here.

References

1. Mukherjee, D. 2022 ESC/ERS guidelines for pulmonary hypertension: key points. American College of Cardiology. August 30, 2022.

2. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731.
 

Pulmonary Vascular Disease Section

Key messages from the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension

1. Per coverage by the American College of Cardiology, “Pulmonary hypertension (PH) is now defined by a mean pulmonary arterial pressure >20 mm Hg at rest. The definition of pulmonary arterial hypertension (PAH) also implies a pulmonary vascular resistance (PVR) >2 Wood units and pulmonary arterial wedge pressure ≤15 mm Hg.”¹ These cut-off values do not translate into new therapeutic recommendations.

2. The diagnostic algorithm for PH now follows a simplified three-step approach, involving first suspicion by first-line physicians, then detection by echocardiography, and confirmation with right heart catheterization, preferably in a PH center.

3. Pulmonary vasoreactivity testing is only recommended in patients with idiopathic PAH, heritable PAH, or drug/toxin associated PAH to identify potential candidates for calcium channel blocker therapy. Inhaled nitric oxide or inhaled iloprost are the recommended agents.

*Mary Jo S. Farmer, MD, PhD
 Member-at-Large

Vijay Balasubramanian, MD, MRCP (UK)
Chair
 

*  The authors for this article were listed in the incorrect order in the print edition of CHEST Physician. The order has been corrected here.

References

1. Mukherjee, D. 2022 ESC/ERS guidelines for pulmonary hypertension: key points. American College of Cardiology. August 30, 2022.

2. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731.
 

Pulmonary Vascular Disease Section

Key messages from the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension

1. Per coverage by the American College of Cardiology, “Pulmonary hypertension (PH) is now defined by a mean pulmonary arterial pressure >20 mm Hg at rest. The definition of pulmonary arterial hypertension (PAH) also implies a pulmonary vascular resistance (PVR) >2 Wood units and pulmonary arterial wedge pressure ≤15 mm Hg.”¹ These cut-off values do not translate into new therapeutic recommendations.

2. The diagnostic algorithm for PH now follows a simplified three-step approach, involving first suspicion by first-line physicians, then detection by echocardiography, and confirmation with right heart catheterization, preferably in a PH center.

3. Pulmonary vasoreactivity testing is only recommended in patients with idiopathic PAH, heritable PAH, or drug/toxin associated PAH to identify potential candidates for calcium channel blocker therapy. Inhaled nitric oxide or inhaled iloprost are the recommended agents.

*Mary Jo S. Farmer, MD, PhD
 Member-at-Large

Vijay Balasubramanian, MD, MRCP (UK)
Chair
 

*  The authors for this article were listed in the incorrect order in the print edition of CHEST Physician. The order has been corrected here.

References

1. Mukherjee, D. 2022 ESC/ERS guidelines for pulmonary hypertension: key points. American College of Cardiology. August 30, 2022.

2. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731.
 

Pulmonary Physiology & Rehabilitation Section

Exercise tolerance in untreated sleep apnea

Numerous cardiovascular, respiratory, neuromuscular, and perceptual factors determine exercise tolerance. This makes designing a study to isolate the contribution of one factor difficult.

A recently published study (Elbehairy, et al. Chest. 2022; published online September 29, 2022) explores exercise tolerance in patients with untreated OSA compared with age- and weight-matched controls. The authors found that at an equivalent work rate, patients with OSA had greater minute ventilation, principally due to higher breathing frequency. Dead space volume, dead space ventilation, and dead space to tidal volume ratio (VD/VT) were higher in patients with OSA, likely due to a reduction in pulmonary vessel recruitment relative to ventilation. VD/VT decreased more from rest to peak in controls than in patients with OSA, an adaptation that is expected with exercise. Patients with OSA had greater arterial stiffness measured by pulse wave velocity and higher blood pressures, which may have affected cardiac output augmentation. Patients with OSA also had higher resting mean pulmonary artery pressures and exercise dyspnea scores. Regression models predicting peak oxygen uptake and peak work rate were statistically significant, with predictors being age, pulse wave velocity, and resting mean pulmonary artery pressure. The role of diastolic dysfunction remains to be determined.

Prior studies have shown that some effects of OSA on exercise may be reversed with CPAP treatment (Arias, et al. Eur Heart J. 2006;27[9]:1106-1113; Chalegre, et al. Sleep Breath. 2021;25[3]:1195-1202). Understanding the mechanisms of exercise limitation in OSA will help physicians address symptoms, reinforce CPAP adherence, and design tailored pulmonary rehabilitation programs.

Fatima Zeba, MD

Fellow-in-Training

Pulmonary Physiology & Rehabilitation Section

Exercise tolerance in untreated sleep apnea

Numerous cardiovascular, respiratory, neuromuscular, and perceptual factors determine exercise tolerance. This makes designing a study to isolate the contribution of one factor difficult.

A recently published study (Elbehairy, et al. Chest. 2022; published online September 29, 2022) explores exercise tolerance in patients with untreated OSA compared with age- and weight-matched controls. The authors found that at an equivalent work rate, patients with OSA had greater minute ventilation, principally due to higher breathing frequency. Dead space volume, dead space ventilation, and dead space to tidal volume ratio (VD/VT) were higher in patients with OSA, likely due to a reduction in pulmonary vessel recruitment relative to ventilation. VD/VT decreased more from rest to peak in controls than in patients with OSA, an adaptation that is expected with exercise. Patients with OSA had greater arterial stiffness measured by pulse wave velocity and higher blood pressures, which may have affected cardiac output augmentation. Patients with OSA also had higher resting mean pulmonary artery pressures and exercise dyspnea scores. Regression models predicting peak oxygen uptake and peak work rate were statistically significant, with predictors being age, pulse wave velocity, and resting mean pulmonary artery pressure. The role of diastolic dysfunction remains to be determined.

Prior studies have shown that some effects of OSA on exercise may be reversed with CPAP treatment (Arias, et al. Eur Heart J. 2006;27[9]:1106-1113; Chalegre, et al. Sleep Breath. 2021;25[3]:1195-1202). Understanding the mechanisms of exercise limitation in OSA will help physicians address symptoms, reinforce CPAP adherence, and design tailored pulmonary rehabilitation programs.

Fatima Zeba, MD

Fellow-in-Training

Pulmonary Physiology & Rehabilitation Section

Exercise tolerance in untreated sleep apnea

Numerous cardiovascular, respiratory, neuromuscular, and perceptual factors determine exercise tolerance. This makes designing a study to isolate the contribution of one factor difficult.

A recently published study (Elbehairy, et al. Chest. 2022; published online September 29, 2022) explores exercise tolerance in patients with untreated OSA compared with age- and weight-matched controls. The authors found that at an equivalent work rate, patients with OSA had greater minute ventilation, principally due to higher breathing frequency. Dead space volume, dead space ventilation, and dead space to tidal volume ratio (VD/VT) were higher in patients with OSA, likely due to a reduction in pulmonary vessel recruitment relative to ventilation. VD/VT decreased more from rest to peak in controls than in patients with OSA, an adaptation that is expected with exercise. Patients with OSA had greater arterial stiffness measured by pulse wave velocity and higher blood pressures, which may have affected cardiac output augmentation. Patients with OSA also had higher resting mean pulmonary artery pressures and exercise dyspnea scores. Regression models predicting peak oxygen uptake and peak work rate were statistically significant, with predictors being age, pulse wave velocity, and resting mean pulmonary artery pressure. The role of diastolic dysfunction remains to be determined.

Prior studies have shown that some effects of OSA on exercise may be reversed with CPAP treatment (Arias, et al. Eur Heart J. 2006;27[9]:1106-1113; Chalegre, et al. Sleep Breath. 2021;25[3]:1195-1202). Understanding the mechanisms of exercise limitation in OSA will help physicians address symptoms, reinforce CPAP adherence, and design tailored pulmonary rehabilitation programs.

Fatima Zeba, MD

Fellow-in-Training