Conference Coverage

Patients with relapsed or refractory B-cell non-Hodgkin lymphomas who are not candidates for hematopoietic stem cell transplant have a generally poor prognosis and few treatment options, but an experimental combination of the antibody-drug conjugate naratuximab with rituximab showed promising efficacy and acceptable safety in these patients in a phase 2 trial.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) the combination was associated with a 44.7% overall response rate, including 31.6% complete responses, and two-thirds of patients had responses lasting more than 12 months, reported Moshe Yair Levy, MD, from Texas Oncology–Baylor Charles A Sammons Cancer Center in Dallas.

“This is, in my viewpoint, very exciting therapy,” he said in a question-and-answer session following his presentation of the data in a late-breaking abstract session during the European Hematology Association annual congress. (Abstract LB1903).

Naratuximab emtansine is an investigational antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against CD37, a surface marker on B lymphocytes that is highly expressed in non-Hodgkin lymphoma (NHL), conjugated to a cytotoxic derivative of maitansine.

CD37 is also an internalizable cell-surface antigen, making it an attractive candidate for an ADC approach.

In a phase 1 trial, naratuximab monotherapy showed a good safety profile and a 22% overall response rate, Dr. Levy noted.

“What they found is that, if you coadminister this ADC with rituximab, you’re actually going to get more internalization of the CD37 monoclonal, therefore more payload delivered to your target cells,” he said.

He reported results of a multicenter, adaptive phase 2 study of the combination in patients with DLBCL and other relapsed/refractory NHL.
 

DLBCL and others

The trial was divided into two parts, with the first consisting of a safety run-in phase with expansion in patients with confirmed diagnoses of relapsed/refractory NHL, including DLBCL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Patients with double- or triple-hit disease (with translocations in MYC plus either BCL2 and/or BCL6), bulky disease, or transformed lymphoma were eligible.

The second part consisted of two cohorts of patients with DLBCL treated with naratuximab and rituximab either weekly or every 3 weeks.

All patients in the study had received one to six prior lines of therapy, and had Eastern Cooperative Oncology Group performance status of 0-2. Patients with CNS lymphomas or prior anti-CD37 targeting therapy were excluded.

The safety population included 50 patients with DLBCL assigned to therapy every 3 weeks, 30 assigned to weekly therapy, and 20 patients with other NHL.
 

DLBCL efficacy

A total of 76 patients with DLBCL were evaluable for efficacy.

The ORR was 44% for patients in both the weekly and every 3 week cohorts, with 31.6% having complete responses.

Among 61 patients with nonbulky disease (longest diameter 7.5 cm or less), the ORR was 50.8%, and among 28 patients who had three or more prior lines of therapy the ORR was 46.4%, with 32.1% having a complete response.

Among responders followed for a median of 15 months, the median duration of response was not reached, and 66% had responses lasting beyond 12 months.

In the weekly dosing DLBCL cohort, 53.3% of patients discontinued treatment of both study drugs because of disease progression, as did 58% of those in the every 3 week cohort, and 30% of patients with other lymphomas. Only eight patients discontinued the combination because of treatment-emergent adverse events. Six patients had treatment-emergent adverse events leading to naratuximab dose reduction.

The most common grade 3 or 4 adverse events were neutropenia, leukopenia, lymphopenia and thrombocytopenias. Dr. Levy commented that the use of granulocyte colony-stimulating factor, which was not mandatory in the study, would likely have lowered the incidence of cytopenias.

There were 10 deaths during the study, 2 of which were considered to be treatment related, occurring in 1 patient each in the DLBCL dosing cohorts; 1 of the patients died from pneumonitis, and the other from left ventricular heart failure.

Other patients deaths were attributed to non–treatment-related cardiac arrest, acute renal failure, exacerbation of chronic heart failure, respiratory failure, multiorgan failure, lung infection, or colon adenocarcinoma.
 

Q 3 weeks suffices

In the question-and-answer session following the presentation, Kenny Lei, MD, from the Chinese University of Hong Kong asked Dr. Levy what the half-life of naratuximab is, and what was the investigator’s rationale for testing a weekly dosing schedule.

“I think the reason they checked the two different regimens, the Q week and the Q 3-week group, is that they noted that [naratuximab] was cleared relatively quickly, and they wanted to see whether or not, by giving Q weekly, when you get a continuous CD37 site occupancy if they would have a better outcome. But as you saw, in the groups there was really no clinically relevant difference in outcome,” Dr. Levy said.

Andrew Davies, MD, PhD, from the University of Southampton (England), asked whether the neutropenia seen in the study was related to myeloid expression of the target of from the off-target deconjugated payload.

“I don’t know that I necessarily have the answer to that,” Dr. Levy replied. “Remember there is the CD20 monoclonal rituximab which we know can cause neutropenia, as well as the CD37 and the target payload. I don’t know if we have enough information to attribute it to one specific component of the therapy,” he said.

The study was funded by Debiopharm International. Dr. Levy disclosed speaker activities for multiple companies, not including Debiopharm. Dr. Lei and Dr. Davies had no disclosures relevant to the study.

Patients with relapsed or refractory B-cell non-Hodgkin lymphomas who are not candidates for hematopoietic stem cell transplant have a generally poor prognosis and few treatment options, but an experimental combination of the antibody-drug conjugate naratuximab with rituximab showed promising efficacy and acceptable safety in these patients in a phase 2 trial.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) the combination was associated with a 44.7% overall response rate, including 31.6% complete responses, and two-thirds of patients had responses lasting more than 12 months, reported Moshe Yair Levy, MD, from Texas Oncology–Baylor Charles A Sammons Cancer Center in Dallas.

“This is, in my viewpoint, very exciting therapy,” he said in a question-and-answer session following his presentation of the data in a late-breaking abstract session during the European Hematology Association annual congress. (Abstract LB1903).

Naratuximab emtansine is an investigational antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against CD37, a surface marker on B lymphocytes that is highly expressed in non-Hodgkin lymphoma (NHL), conjugated to a cytotoxic derivative of maitansine.

CD37 is also an internalizable cell-surface antigen, making it an attractive candidate for an ADC approach.

In a phase 1 trial, naratuximab monotherapy showed a good safety profile and a 22% overall response rate, Dr. Levy noted.

“What they found is that, if you coadminister this ADC with rituximab, you’re actually going to get more internalization of the CD37 monoclonal, therefore more payload delivered to your target cells,” he said.

He reported results of a multicenter, adaptive phase 2 study of the combination in patients with DLBCL and other relapsed/refractory NHL.
 

DLBCL and others

The trial was divided into two parts, with the first consisting of a safety run-in phase with expansion in patients with confirmed diagnoses of relapsed/refractory NHL, including DLBCL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Patients with double- or triple-hit disease (with translocations in MYC plus either BCL2 and/or BCL6), bulky disease, or transformed lymphoma were eligible.

The second part consisted of two cohorts of patients with DLBCL treated with naratuximab and rituximab either weekly or every 3 weeks.

All patients in the study had received one to six prior lines of therapy, and had Eastern Cooperative Oncology Group performance status of 0-2. Patients with CNS lymphomas or prior anti-CD37 targeting therapy were excluded.

The safety population included 50 patients with DLBCL assigned to therapy every 3 weeks, 30 assigned to weekly therapy, and 20 patients with other NHL.
 

DLBCL efficacy

A total of 76 patients with DLBCL were evaluable for efficacy.

The ORR was 44% for patients in both the weekly and every 3 week cohorts, with 31.6% having complete responses.

Among 61 patients with nonbulky disease (longest diameter 7.5 cm or less), the ORR was 50.8%, and among 28 patients who had three or more prior lines of therapy the ORR was 46.4%, with 32.1% having a complete response.

Among responders followed for a median of 15 months, the median duration of response was not reached, and 66% had responses lasting beyond 12 months.

In the weekly dosing DLBCL cohort, 53.3% of patients discontinued treatment of both study drugs because of disease progression, as did 58% of those in the every 3 week cohort, and 30% of patients with other lymphomas. Only eight patients discontinued the combination because of treatment-emergent adverse events. Six patients had treatment-emergent adverse events leading to naratuximab dose reduction.

The most common grade 3 or 4 adverse events were neutropenia, leukopenia, lymphopenia and thrombocytopenias. Dr. Levy commented that the use of granulocyte colony-stimulating factor, which was not mandatory in the study, would likely have lowered the incidence of cytopenias.

There were 10 deaths during the study, 2 of which were considered to be treatment related, occurring in 1 patient each in the DLBCL dosing cohorts; 1 of the patients died from pneumonitis, and the other from left ventricular heart failure.

Other patients deaths were attributed to non–treatment-related cardiac arrest, acute renal failure, exacerbation of chronic heart failure, respiratory failure, multiorgan failure, lung infection, or colon adenocarcinoma.
 

Q 3 weeks suffices

In the question-and-answer session following the presentation, Kenny Lei, MD, from the Chinese University of Hong Kong asked Dr. Levy what the half-life of naratuximab is, and what was the investigator’s rationale for testing a weekly dosing schedule.

“I think the reason they checked the two different regimens, the Q week and the Q 3-week group, is that they noted that [naratuximab] was cleared relatively quickly, and they wanted to see whether or not, by giving Q weekly, when you get a continuous CD37 site occupancy if they would have a better outcome. But as you saw, in the groups there was really no clinically relevant difference in outcome,” Dr. Levy said.

Andrew Davies, MD, PhD, from the University of Southampton (England), asked whether the neutropenia seen in the study was related to myeloid expression of the target of from the off-target deconjugated payload.

“I don’t know that I necessarily have the answer to that,” Dr. Levy replied. “Remember there is the CD20 monoclonal rituximab which we know can cause neutropenia, as well as the CD37 and the target payload. I don’t know if we have enough information to attribute it to one specific component of the therapy,” he said.

The study was funded by Debiopharm International. Dr. Levy disclosed speaker activities for multiple companies, not including Debiopharm. Dr. Lei and Dr. Davies had no disclosures relevant to the study.

Patients with relapsed or refractory B-cell non-Hodgkin lymphomas who are not candidates for hematopoietic stem cell transplant have a generally poor prognosis and few treatment options, but an experimental combination of the antibody-drug conjugate naratuximab with rituximab showed promising efficacy and acceptable safety in these patients in a phase 2 trial.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) the combination was associated with a 44.7% overall response rate, including 31.6% complete responses, and two-thirds of patients had responses lasting more than 12 months, reported Moshe Yair Levy, MD, from Texas Oncology–Baylor Charles A Sammons Cancer Center in Dallas.

“This is, in my viewpoint, very exciting therapy,” he said in a question-and-answer session following his presentation of the data in a late-breaking abstract session during the European Hematology Association annual congress. (Abstract LB1903).

Naratuximab emtansine is an investigational antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against CD37, a surface marker on B lymphocytes that is highly expressed in non-Hodgkin lymphoma (NHL), conjugated to a cytotoxic derivative of maitansine.

CD37 is also an internalizable cell-surface antigen, making it an attractive candidate for an ADC approach.

In a phase 1 trial, naratuximab monotherapy showed a good safety profile and a 22% overall response rate, Dr. Levy noted.

“What they found is that, if you coadminister this ADC with rituximab, you’re actually going to get more internalization of the CD37 monoclonal, therefore more payload delivered to your target cells,” he said.

He reported results of a multicenter, adaptive phase 2 study of the combination in patients with DLBCL and other relapsed/refractory NHL.
 

DLBCL and others

The trial was divided into two parts, with the first consisting of a safety run-in phase with expansion in patients with confirmed diagnoses of relapsed/refractory NHL, including DLBCL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Patients with double- or triple-hit disease (with translocations in MYC plus either BCL2 and/or BCL6), bulky disease, or transformed lymphoma were eligible.

The second part consisted of two cohorts of patients with DLBCL treated with naratuximab and rituximab either weekly or every 3 weeks.

All patients in the study had received one to six prior lines of therapy, and had Eastern Cooperative Oncology Group performance status of 0-2. Patients with CNS lymphomas or prior anti-CD37 targeting therapy were excluded.

The safety population included 50 patients with DLBCL assigned to therapy every 3 weeks, 30 assigned to weekly therapy, and 20 patients with other NHL.
 

DLBCL efficacy

A total of 76 patients with DLBCL were evaluable for efficacy.

The ORR was 44% for patients in both the weekly and every 3 week cohorts, with 31.6% having complete responses.

Among 61 patients with nonbulky disease (longest diameter 7.5 cm or less), the ORR was 50.8%, and among 28 patients who had three or more prior lines of therapy the ORR was 46.4%, with 32.1% having a complete response.

Among responders followed for a median of 15 months, the median duration of response was not reached, and 66% had responses lasting beyond 12 months.

In the weekly dosing DLBCL cohort, 53.3% of patients discontinued treatment of both study drugs because of disease progression, as did 58% of those in the every 3 week cohort, and 30% of patients with other lymphomas. Only eight patients discontinued the combination because of treatment-emergent adverse events. Six patients had treatment-emergent adverse events leading to naratuximab dose reduction.

The most common grade 3 or 4 adverse events were neutropenia, leukopenia, lymphopenia and thrombocytopenias. Dr. Levy commented that the use of granulocyte colony-stimulating factor, which was not mandatory in the study, would likely have lowered the incidence of cytopenias.

There were 10 deaths during the study, 2 of which were considered to be treatment related, occurring in 1 patient each in the DLBCL dosing cohorts; 1 of the patients died from pneumonitis, and the other from left ventricular heart failure.

Other patients deaths were attributed to non–treatment-related cardiac arrest, acute renal failure, exacerbation of chronic heart failure, respiratory failure, multiorgan failure, lung infection, or colon adenocarcinoma.
 

Q 3 weeks suffices

In the question-and-answer session following the presentation, Kenny Lei, MD, from the Chinese University of Hong Kong asked Dr. Levy what the half-life of naratuximab is, and what was the investigator’s rationale for testing a weekly dosing schedule.

“I think the reason they checked the two different regimens, the Q week and the Q 3-week group, is that they noted that [naratuximab] was cleared relatively quickly, and they wanted to see whether or not, by giving Q weekly, when you get a continuous CD37 site occupancy if they would have a better outcome. But as you saw, in the groups there was really no clinically relevant difference in outcome,” Dr. Levy said.

Andrew Davies, MD, PhD, from the University of Southampton (England), asked whether the neutropenia seen in the study was related to myeloid expression of the target of from the off-target deconjugated payload.

“I don’t know that I necessarily have the answer to that,” Dr. Levy replied. “Remember there is the CD20 monoclonal rituximab which we know can cause neutropenia, as well as the CD37 and the target payload. I don’t know if we have enough information to attribute it to one specific component of the therapy,” he said.

The study was funded by Debiopharm International. Dr. Levy disclosed speaker activities for multiple companies, not including Debiopharm. Dr. Lei and Dr. Davies had no disclosures relevant to the study.

Secukinumab (Cosentyx), an interleukin-17A inhibitor, is effective and reasonably well tolerated for treatment of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in children and adolescents, according to a phase 3 trial presented at a late breaking abstracts session of the annual European Congress of Rheumatology.

On the primary outcome of time to flare, the curves for secukinumab and placebo separated almost immediately, with fewer than half the number of flares occurring in the experimental arm over the course of the study, according to Nicolino Ruperto, MD, senior research scientist at IRCCS Istituto Giannina Gaslini in Genoa, Italy.

The trial, called JUNIPERA, was conducted over 2 years and included an open-label treatment period (TP1) and then a randomized, placebo-controlled comparison (TP2). In TP1, 86 children were initiated on open-label secukinumab administered subcutaneously on weeks 1, 2, 3, 4, 8, and 12. The dose was 75 mg for children less than 50 kg and 150 kg for those heavier.
 

Average patient age was 13.1 years

Of these 86 children, 52 had ERA and 34 had JPsA. Disease duration of at least 6 months was required for entry. Patients up to the age of 18 years were permitted to enroll. The average age was 13.1 years. Most patients, two-thirds of whom were male, had received an immunomodulator prior to study entry.

At the end of TP1, 69.9% of patients had achieved 70% improvement in the Juvenile Idiopathic Arthritis American College of Rheumatology joint score (JIA ACR70). The 90.4% of patients who achieved JIA ACR30 were invited to enroll in TP2. A total of 75 patients did so.

At the end of TP2, response rates strongly favored secukinumab over placebo for JIA ACR30 (89.2% vs. 64.9%; P = .014) and JIA ACR70 (67.7% vs. 43.2%; P = .042). Higher but not statistically significant differences in response rates were seen for secukinumab over placebo for JIA ACR50 (78.4% vs. 62.2%; P = .152), JIA ACR90 (51.4% vs. 40.5%; P = .431) and JIA ACR100 (43.2% vs. 37.8%; P = .755).

During TP2, there were 10 flares in the group randomized to secukinumab versus 21 flares in the placebo group, translating by hazard ratio (HR) into a 72% risk reduction (HR, 0.28; P < .001).

Side effects similar to those in adults

The types and rates of serious adverse events were similar to those reported previously in adult patients, according to Dr. Ruperto. Although the rate of serious adverse events (14.6% vs. 10.6%) was only moderately higher in the experimental arm, more patients randomized to secukinumab than placebo discontinued therapy (13.2% vs. 6.3%) before the end of follow-up.

The side effects that occurred more commonly on secukinumab included gastrointestinal complaints, such as diarrhea (22.9% vs. 15.8%). Other adverse events occurring in more than 10% of patients included headache and nasopharyngitis, but most side effects were mild and resolved.

Although the proportion of patients with flare increased over time in both groups, Dr. Ruperto reported that protection against flares and relative improvement in clinical markers of disease activity relative to placebo “were sustained out to 2 years of follow-up.”

The submission of these data to regulatory agencies is anticipated. If secukinumab is given an indication for these forms of arthritis, it will join an indication for plaque psoriasis in children that was granted just a few days before these data were presented. The psoriasis indication is the only current use approved for children in the United States.
 

More biologics needed for JPsA

Additional biologics will be helpful for children with arthritis who are poorly controlled on available treatments, according to Natasha M. Ruth, MD, director of the division of pediatric rheumatology at the Medical University of South Carolina, Charleston. Dr. Ruth was senior author of a case study published 2 years ago in which secukinumab was used to control psoriatic arthritis and nail manifestations of psoriasis.

“It was a girl who had already failed to improve adequately to TNF inhibitors,” reported Dr. Ruth, who had said the child and her parent were very concerned about the nail appearance.

“The nail involvement completely resolved, so it was a very good result in a difficult situation,” Dr. Ruth explained. She said that the decision to try secukinumab was made collaboratively in a clinic in which dermatologists and rheumatologists at her institution work together on difficult cases.

“There is a need for more biologics with different mechanisms of action,” Dr. Ruth said. Based on her experience, secukinumab could be an important addition to treatment options.

Dr. Ruperto reported having financial relationships with more than 20 pharmaceutical companies, including Novartis, which provided financial support for this trial. Many coauthors had financial relationships with multiple companies, including Novartis, and some were employees of the company. Dr. Ruth reported having no potential conflicts of interest.

Secukinumab (Cosentyx), an interleukin-17A inhibitor, is effective and reasonably well tolerated for treatment of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in children and adolescents, according to a phase 3 trial presented at a late breaking abstracts session of the annual European Congress of Rheumatology.

On the primary outcome of time to flare, the curves for secukinumab and placebo separated almost immediately, with fewer than half the number of flares occurring in the experimental arm over the course of the study, according to Nicolino Ruperto, MD, senior research scientist at IRCCS Istituto Giannina Gaslini in Genoa, Italy.

The trial, called JUNIPERA, was conducted over 2 years and included an open-label treatment period (TP1) and then a randomized, placebo-controlled comparison (TP2). In TP1, 86 children were initiated on open-label secukinumab administered subcutaneously on weeks 1, 2, 3, 4, 8, and 12. The dose was 75 mg for children less than 50 kg and 150 kg for those heavier.
 

Average patient age was 13.1 years

Of these 86 children, 52 had ERA and 34 had JPsA. Disease duration of at least 6 months was required for entry. Patients up to the age of 18 years were permitted to enroll. The average age was 13.1 years. Most patients, two-thirds of whom were male, had received an immunomodulator prior to study entry.

At the end of TP1, 69.9% of patients had achieved 70% improvement in the Juvenile Idiopathic Arthritis American College of Rheumatology joint score (JIA ACR70). The 90.4% of patients who achieved JIA ACR30 were invited to enroll in TP2. A total of 75 patients did so.

At the end of TP2, response rates strongly favored secukinumab over placebo for JIA ACR30 (89.2% vs. 64.9%; P = .014) and JIA ACR70 (67.7% vs. 43.2%; P = .042). Higher but not statistically significant differences in response rates were seen for secukinumab over placebo for JIA ACR50 (78.4% vs. 62.2%; P = .152), JIA ACR90 (51.4% vs. 40.5%; P = .431) and JIA ACR100 (43.2% vs. 37.8%; P = .755).

During TP2, there were 10 flares in the group randomized to secukinumab versus 21 flares in the placebo group, translating by hazard ratio (HR) into a 72% risk reduction (HR, 0.28; P < .001).

Side effects similar to those in adults

The types and rates of serious adverse events were similar to those reported previously in adult patients, according to Dr. Ruperto. Although the rate of serious adverse events (14.6% vs. 10.6%) was only moderately higher in the experimental arm, more patients randomized to secukinumab than placebo discontinued therapy (13.2% vs. 6.3%) before the end of follow-up.

The side effects that occurred more commonly on secukinumab included gastrointestinal complaints, such as diarrhea (22.9% vs. 15.8%). Other adverse events occurring in more than 10% of patients included headache and nasopharyngitis, but most side effects were mild and resolved.

Although the proportion of patients with flare increased over time in both groups, Dr. Ruperto reported that protection against flares and relative improvement in clinical markers of disease activity relative to placebo “were sustained out to 2 years of follow-up.”

The submission of these data to regulatory agencies is anticipated. If secukinumab is given an indication for these forms of arthritis, it will join an indication for plaque psoriasis in children that was granted just a few days before these data were presented. The psoriasis indication is the only current use approved for children in the United States.
 

More biologics needed for JPsA

Additional biologics will be helpful for children with arthritis who are poorly controlled on available treatments, according to Natasha M. Ruth, MD, director of the division of pediatric rheumatology at the Medical University of South Carolina, Charleston. Dr. Ruth was senior author of a case study published 2 years ago in which secukinumab was used to control psoriatic arthritis and nail manifestations of psoriasis.

“It was a girl who had already failed to improve adequately to TNF inhibitors,” reported Dr. Ruth, who had said the child and her parent were very concerned about the nail appearance.

“The nail involvement completely resolved, so it was a very good result in a difficult situation,” Dr. Ruth explained. She said that the decision to try secukinumab was made collaboratively in a clinic in which dermatologists and rheumatologists at her institution work together on difficult cases.

“There is a need for more biologics with different mechanisms of action,” Dr. Ruth said. Based on her experience, secukinumab could be an important addition to treatment options.

Dr. Ruperto reported having financial relationships with more than 20 pharmaceutical companies, including Novartis, which provided financial support for this trial. Many coauthors had financial relationships with multiple companies, including Novartis, and some were employees of the company. Dr. Ruth reported having no potential conflicts of interest.

Secukinumab (Cosentyx), an interleukin-17A inhibitor, is effective and reasonably well tolerated for treatment of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in children and adolescents, according to a phase 3 trial presented at a late breaking abstracts session of the annual European Congress of Rheumatology.

On the primary outcome of time to flare, the curves for secukinumab and placebo separated almost immediately, with fewer than half the number of flares occurring in the experimental arm over the course of the study, according to Nicolino Ruperto, MD, senior research scientist at IRCCS Istituto Giannina Gaslini in Genoa, Italy.

The trial, called JUNIPERA, was conducted over 2 years and included an open-label treatment period (TP1) and then a randomized, placebo-controlled comparison (TP2). In TP1, 86 children were initiated on open-label secukinumab administered subcutaneously on weeks 1, 2, 3, 4, 8, and 12. The dose was 75 mg for children less than 50 kg and 150 kg for those heavier.
 

Average patient age was 13.1 years

Of these 86 children, 52 had ERA and 34 had JPsA. Disease duration of at least 6 months was required for entry. Patients up to the age of 18 years were permitted to enroll. The average age was 13.1 years. Most patients, two-thirds of whom were male, had received an immunomodulator prior to study entry.

At the end of TP1, 69.9% of patients had achieved 70% improvement in the Juvenile Idiopathic Arthritis American College of Rheumatology joint score (JIA ACR70). The 90.4% of patients who achieved JIA ACR30 were invited to enroll in TP2. A total of 75 patients did so.

At the end of TP2, response rates strongly favored secukinumab over placebo for JIA ACR30 (89.2% vs. 64.9%; P = .014) and JIA ACR70 (67.7% vs. 43.2%; P = .042). Higher but not statistically significant differences in response rates were seen for secukinumab over placebo for JIA ACR50 (78.4% vs. 62.2%; P = .152), JIA ACR90 (51.4% vs. 40.5%; P = .431) and JIA ACR100 (43.2% vs. 37.8%; P = .755).

During TP2, there were 10 flares in the group randomized to secukinumab versus 21 flares in the placebo group, translating by hazard ratio (HR) into a 72% risk reduction (HR, 0.28; P < .001).

Side effects similar to those in adults

The types and rates of serious adverse events were similar to those reported previously in adult patients, according to Dr. Ruperto. Although the rate of serious adverse events (14.6% vs. 10.6%) was only moderately higher in the experimental arm, more patients randomized to secukinumab than placebo discontinued therapy (13.2% vs. 6.3%) before the end of follow-up.

The side effects that occurred more commonly on secukinumab included gastrointestinal complaints, such as diarrhea (22.9% vs. 15.8%). Other adverse events occurring in more than 10% of patients included headache and nasopharyngitis, but most side effects were mild and resolved.

Although the proportion of patients with flare increased over time in both groups, Dr. Ruperto reported that protection against flares and relative improvement in clinical markers of disease activity relative to placebo “were sustained out to 2 years of follow-up.”

The submission of these data to regulatory agencies is anticipated. If secukinumab is given an indication for these forms of arthritis, it will join an indication for plaque psoriasis in children that was granted just a few days before these data were presented. The psoriasis indication is the only current use approved for children in the United States.
 

More biologics needed for JPsA

Additional biologics will be helpful for children with arthritis who are poorly controlled on available treatments, according to Natasha M. Ruth, MD, director of the division of pediatric rheumatology at the Medical University of South Carolina, Charleston. Dr. Ruth was senior author of a case study published 2 years ago in which secukinumab was used to control psoriatic arthritis and nail manifestations of psoriasis.

“It was a girl who had already failed to improve adequately to TNF inhibitors,” reported Dr. Ruth, who had said the child and her parent were very concerned about the nail appearance.

“The nail involvement completely resolved, so it was a very good result in a difficult situation,” Dr. Ruth explained. She said that the decision to try secukinumab was made collaboratively in a clinic in which dermatologists and rheumatologists at her institution work together on difficult cases.

“There is a need for more biologics with different mechanisms of action,” Dr. Ruth said. Based on her experience, secukinumab could be an important addition to treatment options.

Dr. Ruperto reported having financial relationships with more than 20 pharmaceutical companies, including Novartis, which provided financial support for this trial. Many coauthors had financial relationships with multiple companies, including Novartis, and some were employees of the company. Dr. Ruth reported having no potential conflicts of interest.

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

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

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

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

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

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

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

It may not be always necessary to approach the treatment of HER2-positive, hormone receptor–negative (HER2+/HR–) early breast cancer with added chemotherapy, survival results of a prospective multicenter randomized trial suggest.

In the ADAPT-HER2+/HR– trial, comparing a de-escalated 12-week neoadjuvant regimen consisting of dual HER2 blockade with trastuzumab (Herceptin) and pertuzumab (Perjeta) with or without weekly paclitaxel, the three-drug regimen was associated with high pathologic complete response(pCR) rates and excellent 5-year survival, irrespective of whether patients received additional chemotherapy, reported Nadia Harbeck, MD, PhD, of the University of Munich.

“Chemotherapy-free regimens are promising in highly sensitive tumors with early response, but future investigation of such chemotherapy-free regimens need to be focused on selected patients, like those with HER2 3+ tumors, non–basal-like tumors, those showing early response to the de-escalated therapy, and those with predictive RNA signatures such as immune signatures,” she said in an oral abstract session during the American Society of Clinical Oncology annual meeting (Abstract 503).
 

Under the WGS umbrella

The ADAPT HER2+/HR– trial (NCT01779206) is one of several conducted by the West German Study Group (WGS) on therapy for intrinsic breast cancer types.

In this study, 134 patients with HER2-positive, estrogen and progesterone receptor–negative tumors with no metastatic disease and good performance status were assigned on a 5:2 basis to neoadjuvant therapy with trastuzumab at a loading dose of 8 mg/kg for the first cycle followed by 6 mg/kg for subsequent cycles every 3 weeks x 4, plus pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks x 4 (92 patients), or to trastuzumab and pertuzumab at the same dose and schedule plus paclitaxel 80 mg/m² once weekly for 12 weeks.

Patients had surgery within 3 weeks of the end of study therapy unless they did not have a histologically confirmed pCR, in which case they went on to receive standard neoadjuvant therapy prior to surgery.

Adjuvant therapy was performed according to national guidelines, although patients with a pCR after 12 weeks of study therapy could be spared from adjuvant chemotherapy at the investigator’s discretion.

Patients underwent biopsy at 3 weeks for therapy for early response assessment, defined as either a Ki67 decrease of at least 30% from baseline, or low cellularity (less than 500 invasive tumor cells).
 

First survival results

The investigators previously reported the primary pCR endpoint from the trial, which showed a rate of 90% after 12 weeks in the three-drug arm, and a “substantial and clinically meaningful” pCR rate of 34% after the trastuzumab plus pertuzumab alone.

At ASCO 2021, Dr. Harbeck reported the first survival data from the trial.

After a median follow-up of 59.9 months, there were no statistically significant differences between trial arms in either overall survival, invasive disease-free survival (iDFS), or distant disease-free survival (dDFS).

The 5-year iDFS rate in the three-drug arm was 98%, compared with 87% for the dual HER2 blockade-only arm, a difference that was not statistically significant.

The 5-year dDFS rates were 98% and 92% respectively. There were only seven dDFS events during follow-up, Dr. Harbeck noted.

There were only six deaths during follow-up, with overall survival rates of 98% in the paclitaxel-containing arm, and 94% in the anti-HER2 antibodies–only arm, a difference of one overall survival event, Dr. Harbeck said.
 

pCR counts

However, patients who did not have pathologic complete responses at the end of first-line de-escalated therapy had worse outcomes, with a 5-year iDFS rate of 82%, compared with 98% for patients who had achieved a pCR. This translated into a hazard ratio for invasive disease in patients with pCRs of 0.14 (P = .011).

This difference occurred despite the study requirement that all patients who did not have pCR after 12 weeks of initial therapy would receive additional chemotherapy.

Looking at the tumor subtype among patients in the paclitaxel-free arm to see whether they could identify predictors of early response, the researchers found a pCR rate of 36.5% among 85 patients with nonbasal tumors, but 0% among 7 patients with basal tumors.

The investigators identified a population of patients whose tumors could be considered nonsensitive to dual HER2 blockade alone: Those with basal tumors, those tumors with low immunohistochemical HER2 expression, and those without an early response to therapy on biopsy 3 weeks into initial therapy. Among 31 of the 92 patients in the dual HER2 arm who met this description, 2 had pCRs, Dr. Harbeck noted.

The 5-year iDFS rate among patients in the dual blockade–only arm with nonsensitive tumors was 79%, compared with 93% for patients with treatment-responsive types, although there were only 13 invasive events total in this arm.

“If we look at the whole trial population, the negative prognostic impact of what we termed nonsensitive tumors was even significant regarding dDFS, with a hazard ratio of about 5,” she said.
 

‘A consistent theme’

Invited discussant Lisa A. Carey, MD, ScM, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, noted that the trial was underpowered for outcomes, but that results nonetheless suggest that patients with strongly HER2-driven tumors might get comparable benefits from less chemotherapy.

“This trial included only hormone receptor–negative, HER2-positive tumors, and these we know are likely to be HER2-enriched in terms of subtype, about three-quarters of them,”she said.

The previously reported pCR rate of 90% in the paclitaxel-containing arm, with 80% of patients requiring no further chemotherapy, resulted in the excellent 5-year iDFS and dDFS in this group, despite the relatively highly clinical stage, with about 60% of patients having clinical stage 2 or higher tumors, and more than 40% being node positive.

The idea that pCR itself can predict which patients could be spared from more intensive chemotherapy “is starting to look like a consistent theme,” she said.

Dr. Carey pointed out that in the KRISTINE trial comparing the combination of trastuzumab emtansine (T-DM1) and pertuzumab with standard chemotherapy in patients with HER2-positive stage I-III breast cancer, although the experimental combination was associated with lower pCR rates and worse event-free survival, rates of iDFS/dDFS were virtually identical for patients in both arms who achieved a pCR.

“So the question is can pCR mean that we can either eliminate additional therapy,” she said, noting that the question is currently being addressed prospectively in two clinical trials, COMPASS-pCR and DECRESCENDO.

ADAPT HER2+/HR- is sponsored by F. Hoffman-La Roche. Dr. Harbeck disclosed institutional research funding from Roche/Genentech, as well as honoraria and consulting/advising for multiple companies. Dr. Carey disclosed institutional research funding and other relationships with various companies.

It may not be always necessary to approach the treatment of HER2-positive, hormone receptor–negative (HER2+/HR–) early breast cancer with added chemotherapy, survival results of a prospective multicenter randomized trial suggest.

In the ADAPT-HER2+/HR– trial, comparing a de-escalated 12-week neoadjuvant regimen consisting of dual HER2 blockade with trastuzumab (Herceptin) and pertuzumab (Perjeta) with or without weekly paclitaxel, the three-drug regimen was associated with high pathologic complete response(pCR) rates and excellent 5-year survival, irrespective of whether patients received additional chemotherapy, reported Nadia Harbeck, MD, PhD, of the University of Munich.

“Chemotherapy-free regimens are promising in highly sensitive tumors with early response, but future investigation of such chemotherapy-free regimens need to be focused on selected patients, like those with HER2 3+ tumors, non–basal-like tumors, those showing early response to the de-escalated therapy, and those with predictive RNA signatures such as immune signatures,” she said in an oral abstract session during the American Society of Clinical Oncology annual meeting (Abstract 503).
 

Under the WGS umbrella

The ADAPT HER2+/HR– trial (NCT01779206) is one of several conducted by the West German Study Group (WGS) on therapy for intrinsic breast cancer types.

In this study, 134 patients with HER2-positive, estrogen and progesterone receptor–negative tumors with no metastatic disease and good performance status were assigned on a 5:2 basis to neoadjuvant therapy with trastuzumab at a loading dose of 8 mg/kg for the first cycle followed by 6 mg/kg for subsequent cycles every 3 weeks x 4, plus pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks x 4 (92 patients), or to trastuzumab and pertuzumab at the same dose and schedule plus paclitaxel 80 mg/m² once weekly for 12 weeks.

Patients had surgery within 3 weeks of the end of study therapy unless they did not have a histologically confirmed pCR, in which case they went on to receive standard neoadjuvant therapy prior to surgery.

Adjuvant therapy was performed according to national guidelines, although patients with a pCR after 12 weeks of study therapy could be spared from adjuvant chemotherapy at the investigator’s discretion.

Patients underwent biopsy at 3 weeks for therapy for early response assessment, defined as either a Ki67 decrease of at least 30% from baseline, or low cellularity (less than 500 invasive tumor cells).
 

First survival results

The investigators previously reported the primary pCR endpoint from the trial, which showed a rate of 90% after 12 weeks in the three-drug arm, and a “substantial and clinically meaningful” pCR rate of 34% after the trastuzumab plus pertuzumab alone.

At ASCO 2021, Dr. Harbeck reported the first survival data from the trial.

After a median follow-up of 59.9 months, there were no statistically significant differences between trial arms in either overall survival, invasive disease-free survival (iDFS), or distant disease-free survival (dDFS).

The 5-year iDFS rate in the three-drug arm was 98%, compared with 87% for the dual HER2 blockade-only arm, a difference that was not statistically significant.

The 5-year dDFS rates were 98% and 92% respectively. There were only seven dDFS events during follow-up, Dr. Harbeck noted.

There were only six deaths during follow-up, with overall survival rates of 98% in the paclitaxel-containing arm, and 94% in the anti-HER2 antibodies–only arm, a difference of one overall survival event, Dr. Harbeck said.
 

pCR counts

However, patients who did not have pathologic complete responses at the end of first-line de-escalated therapy had worse outcomes, with a 5-year iDFS rate of 82%, compared with 98% for patients who had achieved a pCR. This translated into a hazard ratio for invasive disease in patients with pCRs of 0.14 (P = .011).

This difference occurred despite the study requirement that all patients who did not have pCR after 12 weeks of initial therapy would receive additional chemotherapy.

Looking at the tumor subtype among patients in the paclitaxel-free arm to see whether they could identify predictors of early response, the researchers found a pCR rate of 36.5% among 85 patients with nonbasal tumors, but 0% among 7 patients with basal tumors.

The investigators identified a population of patients whose tumors could be considered nonsensitive to dual HER2 blockade alone: Those with basal tumors, those tumors with low immunohistochemical HER2 expression, and those without an early response to therapy on biopsy 3 weeks into initial therapy. Among 31 of the 92 patients in the dual HER2 arm who met this description, 2 had pCRs, Dr. Harbeck noted.

The 5-year iDFS rate among patients in the dual blockade–only arm with nonsensitive tumors was 79%, compared with 93% for patients with treatment-responsive types, although there were only 13 invasive events total in this arm.

“If we look at the whole trial population, the negative prognostic impact of what we termed nonsensitive tumors was even significant regarding dDFS, with a hazard ratio of about 5,” she said.
 

‘A consistent theme’

Invited discussant Lisa A. Carey, MD, ScM, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, noted that the trial was underpowered for outcomes, but that results nonetheless suggest that patients with strongly HER2-driven tumors might get comparable benefits from less chemotherapy.

“This trial included only hormone receptor–negative, HER2-positive tumors, and these we know are likely to be HER2-enriched in terms of subtype, about three-quarters of them,”she said.

The previously reported pCR rate of 90% in the paclitaxel-containing arm, with 80% of patients requiring no further chemotherapy, resulted in the excellent 5-year iDFS and dDFS in this group, despite the relatively highly clinical stage, with about 60% of patients having clinical stage 2 or higher tumors, and more than 40% being node positive.

The idea that pCR itself can predict which patients could be spared from more intensive chemotherapy “is starting to look like a consistent theme,” she said.

Dr. Carey pointed out that in the KRISTINE trial comparing the combination of trastuzumab emtansine (T-DM1) and pertuzumab with standard chemotherapy in patients with HER2-positive stage I-III breast cancer, although the experimental combination was associated with lower pCR rates and worse event-free survival, rates of iDFS/dDFS were virtually identical for patients in both arms who achieved a pCR.

“So the question is can pCR mean that we can either eliminate additional therapy,” she said, noting that the question is currently being addressed prospectively in two clinical trials, COMPASS-pCR and DECRESCENDO.

ADAPT HER2+/HR- is sponsored by F. Hoffman-La Roche. Dr. Harbeck disclosed institutional research funding from Roche/Genentech, as well as honoraria and consulting/advising for multiple companies. Dr. Carey disclosed institutional research funding and other relationships with various companies.

It may not be always necessary to approach the treatment of HER2-positive, hormone receptor–negative (HER2+/HR–) early breast cancer with added chemotherapy, survival results of a prospective multicenter randomized trial suggest.

In the ADAPT-HER2+/HR– trial, comparing a de-escalated 12-week neoadjuvant regimen consisting of dual HER2 blockade with trastuzumab (Herceptin) and pertuzumab (Perjeta) with or without weekly paclitaxel, the three-drug regimen was associated with high pathologic complete response(pCR) rates and excellent 5-year survival, irrespective of whether patients received additional chemotherapy, reported Nadia Harbeck, MD, PhD, of the University of Munich.

“Chemotherapy-free regimens are promising in highly sensitive tumors with early response, but future investigation of such chemotherapy-free regimens need to be focused on selected patients, like those with HER2 3+ tumors, non–basal-like tumors, those showing early response to the de-escalated therapy, and those with predictive RNA signatures such as immune signatures,” she said in an oral abstract session during the American Society of Clinical Oncology annual meeting (Abstract 503).
 

Under the WGS umbrella

The ADAPT HER2+/HR– trial (NCT01779206) is one of several conducted by the West German Study Group (WGS) on therapy for intrinsic breast cancer types.

In this study, 134 patients with HER2-positive, estrogen and progesterone receptor–negative tumors with no metastatic disease and good performance status were assigned on a 5:2 basis to neoadjuvant therapy with trastuzumab at a loading dose of 8 mg/kg for the first cycle followed by 6 mg/kg for subsequent cycles every 3 weeks x 4, plus pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks x 4 (92 patients), or to trastuzumab and pertuzumab at the same dose and schedule plus paclitaxel 80 mg/m² once weekly for 12 weeks.

Patients had surgery within 3 weeks of the end of study therapy unless they did not have a histologically confirmed pCR, in which case they went on to receive standard neoadjuvant therapy prior to surgery.

Adjuvant therapy was performed according to national guidelines, although patients with a pCR after 12 weeks of study therapy could be spared from adjuvant chemotherapy at the investigator’s discretion.

Patients underwent biopsy at 3 weeks for therapy for early response assessment, defined as either a Ki67 decrease of at least 30% from baseline, or low cellularity (less than 500 invasive tumor cells).
 

First survival results

The investigators previously reported the primary pCR endpoint from the trial, which showed a rate of 90% after 12 weeks in the three-drug arm, and a “substantial and clinically meaningful” pCR rate of 34% after the trastuzumab plus pertuzumab alone.

At ASCO 2021, Dr. Harbeck reported the first survival data from the trial.

After a median follow-up of 59.9 months, there were no statistically significant differences between trial arms in either overall survival, invasive disease-free survival (iDFS), or distant disease-free survival (dDFS).

The 5-year iDFS rate in the three-drug arm was 98%, compared with 87% for the dual HER2 blockade-only arm, a difference that was not statistically significant.

The 5-year dDFS rates were 98% and 92% respectively. There were only seven dDFS events during follow-up, Dr. Harbeck noted.

There were only six deaths during follow-up, with overall survival rates of 98% in the paclitaxel-containing arm, and 94% in the anti-HER2 antibodies–only arm, a difference of one overall survival event, Dr. Harbeck said.
 

pCR counts

However, patients who did not have pathologic complete responses at the end of first-line de-escalated therapy had worse outcomes, with a 5-year iDFS rate of 82%, compared with 98% for patients who had achieved a pCR. This translated into a hazard ratio for invasive disease in patients with pCRs of 0.14 (P = .011).

This difference occurred despite the study requirement that all patients who did not have pCR after 12 weeks of initial therapy would receive additional chemotherapy.

Looking at the tumor subtype among patients in the paclitaxel-free arm to see whether they could identify predictors of early response, the researchers found a pCR rate of 36.5% among 85 patients with nonbasal tumors, but 0% among 7 patients with basal tumors.

The investigators identified a population of patients whose tumors could be considered nonsensitive to dual HER2 blockade alone: Those with basal tumors, those tumors with low immunohistochemical HER2 expression, and those without an early response to therapy on biopsy 3 weeks into initial therapy. Among 31 of the 92 patients in the dual HER2 arm who met this description, 2 had pCRs, Dr. Harbeck noted.

The 5-year iDFS rate among patients in the dual blockade–only arm with nonsensitive tumors was 79%, compared with 93% for patients with treatment-responsive types, although there were only 13 invasive events total in this arm.

“If we look at the whole trial population, the negative prognostic impact of what we termed nonsensitive tumors was even significant regarding dDFS, with a hazard ratio of about 5,” she said.
 

‘A consistent theme’

Invited discussant Lisa A. Carey, MD, ScM, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, noted that the trial was underpowered for outcomes, but that results nonetheless suggest that patients with strongly HER2-driven tumors might get comparable benefits from less chemotherapy.

“This trial included only hormone receptor–negative, HER2-positive tumors, and these we know are likely to be HER2-enriched in terms of subtype, about three-quarters of them,”she said.

The previously reported pCR rate of 90% in the paclitaxel-containing arm, with 80% of patients requiring no further chemotherapy, resulted in the excellent 5-year iDFS and dDFS in this group, despite the relatively highly clinical stage, with about 60% of patients having clinical stage 2 or higher tumors, and more than 40% being node positive.

The idea that pCR itself can predict which patients could be spared from more intensive chemotherapy “is starting to look like a consistent theme,” she said.

Dr. Carey pointed out that in the KRISTINE trial comparing the combination of trastuzumab emtansine (T-DM1) and pertuzumab with standard chemotherapy in patients with HER2-positive stage I-III breast cancer, although the experimental combination was associated with lower pCR rates and worse event-free survival, rates of iDFS/dDFS were virtually identical for patients in both arms who achieved a pCR.

“So the question is can pCR mean that we can either eliminate additional therapy,” she said, noting that the question is currently being addressed prospectively in two clinical trials, COMPASS-pCR and DECRESCENDO.

ADAPT HER2+/HR- is sponsored by F. Hoffman-La Roche. Dr. Harbeck disclosed institutional research funding from Roche/Genentech, as well as honoraria and consulting/advising for multiple companies. Dr. Carey disclosed institutional research funding and other relationships with various companies.

Pyoderma gangrenosum (PG), a rare and painful ulcerative skin disorder, requires special care because “it’s a challenging diagnosis to make” and is frequently linked to serious comorbid conditions, a dermatologist told colleagues.

PG is also challenging to manage, said Jeffrey Callen, MD, professor and chief of the division of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease. “There are multiple treatments, but few have a high level of evidence to document their efficacy.”

PG is a neutrophilic dermatosis that usually occurs with a small lesion, often pustular, that spreads, and is a diagnosis of exclusion. “There’s no way you can possibly exclude everything, but the major things that have to be excluded are infection and malignancies,” he said. “Doing a good history and physical examination is critical, and a biopsy should be done in the vast majority of patients.”

Cultures and routine labs should be obtained, said Dr. Callen, highlighting tests that measure immunofixation (IFE), antineutrophil cytoplasmic antibodies (ANCE), anticardiolipin antibody (aCL), and lupus anticoagulant (LA).

Bowel and bone marrow tests may be appropriate in some patients, he said, noting that about half of PG cases are linked to comorbid conditions such as inflammatory bowel disease (IBD), arthritis, and hematologic diseases.

Dr. Callen also made the following points about making the diagnosis:

• Several clinical variants exist: classic, peristomal, and atypical.
• Pathergy – hyperreactivity of skin to injury – occurs in about a third of patients.
• Neutrophilic infiltrates may occur in other organs.
• Numerous drugs, including isotretinoin, can cause PG.
• PG may be misdiagnosed as necrotizing fasciitis.
• Several diagnostic frameworks exist: the Su Criteria, the PARACELCUS Score, and the Delphi Consensus Criteria. The Delphi criteria identified the highest percentage of cases (89%) in a study comparing the three, published in 2020. The frameworks “are helpful in the clinic, but they are not to be used as criteria for diagnosis. They’re really for classification,” Dr. Callen said.

Once the diagnosis has been made, he said, focus on healing the wound, which he said “can be done as any other wound would be healed,” and calming the inflammation.

“Patients who have mild disease might be treated with lower doses of prednisone, topical medications, or intralesional injections,” he said. “Corticosteroids are never wrong in the beginning.” Some patients may have genetic abnormalities related to PG, he added, and medications that target them may be appropriate.

Antibiotics and biologic agents, particularly TNF-alpha inhibitors, are possible treatments, Dr. Callen said. He highlighted a 2018 systematic review that evaluated treatments and found the most evidence supported systemic corticosteroids, cyclosporine, and TNF-alpha inhibitors. However, the quality of studies was limited, and the authors noted that the lesions frequently failed to respond or recurred.

When appropriate, surgery can be performed, he said.

Dr. Callen reported no relevant disclosures.

Pyoderma gangrenosum (PG), a rare and painful ulcerative skin disorder, requires special care because “it’s a challenging diagnosis to make” and is frequently linked to serious comorbid conditions, a dermatologist told colleagues.

PG is also challenging to manage, said Jeffrey Callen, MD, professor and chief of the division of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease. “There are multiple treatments, but few have a high level of evidence to document their efficacy.”

PG is a neutrophilic dermatosis that usually occurs with a small lesion, often pustular, that spreads, and is a diagnosis of exclusion. “There’s no way you can possibly exclude everything, but the major things that have to be excluded are infection and malignancies,” he said. “Doing a good history and physical examination is critical, and a biopsy should be done in the vast majority of patients.”

Cultures and routine labs should be obtained, said Dr. Callen, highlighting tests that measure immunofixation (IFE), antineutrophil cytoplasmic antibodies (ANCE), anticardiolipin antibody (aCL), and lupus anticoagulant (LA).

Bowel and bone marrow tests may be appropriate in some patients, he said, noting that about half of PG cases are linked to comorbid conditions such as inflammatory bowel disease (IBD), arthritis, and hematologic diseases.

Dr. Callen also made the following points about making the diagnosis:

• Several clinical variants exist: classic, peristomal, and atypical.
• Pathergy – hyperreactivity of skin to injury – occurs in about a third of patients.
• Neutrophilic infiltrates may occur in other organs.
• Numerous drugs, including isotretinoin, can cause PG.
• PG may be misdiagnosed as necrotizing fasciitis.
• Several diagnostic frameworks exist: the Su Criteria, the PARACELCUS Score, and the Delphi Consensus Criteria. The Delphi criteria identified the highest percentage of cases (89%) in a study comparing the three, published in 2020. The frameworks “are helpful in the clinic, but they are not to be used as criteria for diagnosis. They’re really for classification,” Dr. Callen said.

Once the diagnosis has been made, he said, focus on healing the wound, which he said “can be done as any other wound would be healed,” and calming the inflammation.

“Patients who have mild disease might be treated with lower doses of prednisone, topical medications, or intralesional injections,” he said. “Corticosteroids are never wrong in the beginning.” Some patients may have genetic abnormalities related to PG, he added, and medications that target them may be appropriate.

Antibiotics and biologic agents, particularly TNF-alpha inhibitors, are possible treatments, Dr. Callen said. He highlighted a 2018 systematic review that evaluated treatments and found the most evidence supported systemic corticosteroids, cyclosporine, and TNF-alpha inhibitors. However, the quality of studies was limited, and the authors noted that the lesions frequently failed to respond or recurred.

When appropriate, surgery can be performed, he said.

Dr. Callen reported no relevant disclosures.

Pyoderma gangrenosum (PG), a rare and painful ulcerative skin disorder, requires special care because “it’s a challenging diagnosis to make” and is frequently linked to serious comorbid conditions, a dermatologist told colleagues.

PG is also challenging to manage, said Jeffrey Callen, MD, professor and chief of the division of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease. “There are multiple treatments, but few have a high level of evidence to document their efficacy.”

PG is a neutrophilic dermatosis that usually occurs with a small lesion, often pustular, that spreads, and is a diagnosis of exclusion. “There’s no way you can possibly exclude everything, but the major things that have to be excluded are infection and malignancies,” he said. “Doing a good history and physical examination is critical, and a biopsy should be done in the vast majority of patients.”

Cultures and routine labs should be obtained, said Dr. Callen, highlighting tests that measure immunofixation (IFE), antineutrophil cytoplasmic antibodies (ANCE), anticardiolipin antibody (aCL), and lupus anticoagulant (LA).

Bowel and bone marrow tests may be appropriate in some patients, he said, noting that about half of PG cases are linked to comorbid conditions such as inflammatory bowel disease (IBD), arthritis, and hematologic diseases.

Dr. Callen also made the following points about making the diagnosis:

• Several clinical variants exist: classic, peristomal, and atypical.
• Pathergy – hyperreactivity of skin to injury – occurs in about a third of patients.
• Neutrophilic infiltrates may occur in other organs.
• Numerous drugs, including isotretinoin, can cause PG.
• PG may be misdiagnosed as necrotizing fasciitis.
• Several diagnostic frameworks exist: the Su Criteria, the PARACELCUS Score, and the Delphi Consensus Criteria. The Delphi criteria identified the highest percentage of cases (89%) in a study comparing the three, published in 2020. The frameworks “are helpful in the clinic, but they are not to be used as criteria for diagnosis. They’re really for classification,” Dr. Callen said.

Once the diagnosis has been made, he said, focus on healing the wound, which he said “can be done as any other wound would be healed,” and calming the inflammation.

“Patients who have mild disease might be treated with lower doses of prednisone, topical medications, or intralesional injections,” he said. “Corticosteroids are never wrong in the beginning.” Some patients may have genetic abnormalities related to PG, he added, and medications that target them may be appropriate.

Antibiotics and biologic agents, particularly TNF-alpha inhibitors, are possible treatments, Dr. Callen said. He highlighted a 2018 systematic review that evaluated treatments and found the most evidence supported systemic corticosteroids, cyclosporine, and TNF-alpha inhibitors. However, the quality of studies was limited, and the authors noted that the lesions frequently failed to respond or recurred.

When appropriate, surgery can be performed, he said.

Dr. Callen reported no relevant disclosures.

During the annual conference of the American Society for Laser Medicine and Surgery, H. Ray Jalian, MD, shared his “top 10” tips and tricks for everyday cosmetic practice, based on nearly 10 years of experience treating patients on both coasts of the United States.

They are as follows:

1. Know your clinical endpoints. “One of the things that was drilled into me during my fellowship in lasers and cosmetics at Mass General was to know your clinical endpoints and to avoid a cookbook approach,” said Dr. Jalian, who practices dermatology in Los Angeles. “You should treat based on the pathology that you’re seeing on the skin and let the endpoints be your guide. The skin will tell you what you’re doing right, and the skin will tell you what you’re doing wrong. Picking up on these cues will allow you to deliver a safe and effective treatment to your patients.”

The selection of proper treatment parameters is driven by selective photothermolysis, a microsurgery technique that uses customized wavelengths, pulse durations, and fluences to target a chromophore. “Knowing the size and shape of your target allows you to pick the right pulse duration,” he said. “This is dictated by thermal relaxation time, which is proportional to the size and shape of the target. Smaller targets require a shorter pulse width, while larger targets require a longer pulse width.”

2. Do not perform a procedure for which you cannot recognize and treat the side effects. “I can’t tell you how many times I’ve gotten referrals from outside providers with a side effect that, if it had been recognized and treated, would have been inconsequential long-term for the patient,” Dr. Jalian said. “You can only avoid complications by not firing the laser. The more you practice, the more complications you’re going to have. This is inevitable, but good practice and common sense can reduce complications significantly.”

Even the most skilled clinicians encounter side effects from time to time. “The most important thing is to form a network of physicians you trust that you can call or text when you need help in managing a particular complication,” he continued. “This happens to all of us,” he said. Don’t be afraid to phone a colleague, he advised, “and get a fresh set of eyes because oftentimes they can provide insights, especially when you’re having tunnel vision during a complication, that can ultimately result in better patient care.”

3. Don’t forget your clinical training. “Trust your clinical judgment,” Dr. Jalian said. “If something doesn’t seem right, even if it was a case referred to you by experienced practitioners, you are a clinician first and foremost, and you are allowed to make a clinical judgment on lesions.” He referred to a 2011 report in which the authors described a series of four cases where patients presented for cosmetic evaluation of vascular lesions that turned out to be more significant pathologic disease. “Trust your clinical insight because this will serve you in the long term,” he said.

4. Set realistic expectations. Patients with unrealistically high expectations are likely to express dissatisfaction with their treatment results, “no matter how good of a job you do,” Dr. Jalian said. “In addition to safely treating the patient, we strive for patient satisfaction, because with these elective procedures we’re trying to give a patient a result they’re looking for. But our No. 1 job is also to be realistic about the results we can obtain. If someone comes in wanting treatment with a skin-tightening device but clearly needs a face-lift because they have too much laxity, your job is to tell them that this is not the appropriate device for them. Learn the art of saying no. If handled correctly, the patient will often thank you before she heads out the door. Ultimately, honesty is the best policy. I may say something like, ‘I’m not telling you the answer you want to hear, I’m telling you the truth.’ That often goes over well.”

5. Use proper anesthesia. Patients come to you for results, but they’re also likely to remember how well you controlled their pain during procedures. Strategies favored by Dr. Jalian include applying extra topical anesthetic to “hot spots” and splitting up treatment sessions when tackling a large area. “Consider using adjunctive analgesics such as oral medications and nitrous oxide,” he added. Other options, he said, are cooling techniques and distraction techniques, such as the use of a stress ball, consideration of the gate control theory of pain, and “talkesthesia”(using conversation to distract the patient).

6. Obtain proper informed consent. A lack of informed consent ranks as a common reason why doctors get sued. “This happens when a physician fails to inform the patient of all medically reasonable alternatives and their risks, even for noninvasive procedures prior to administering treatment,” Dr. Jalian said. “All patients have the right to an informed consent prior to any treatment. It doesn’t necessarily have to be in a written form, but it’s important to at least have a discussion and document it for all procedures, including medical and cosmetic procedures and oral and topical treatments. Keep it simple. A written consent is ineffective if the patient does not understand material about the procedure.” Avoid the use of excessive medical terms. For example, use bruising instead of purpura, redness instead of erythema, and drooping instead of ptosis.

7. Lower the laser treatment density for darker skin types. According to Dr. Jalian, several clinical studies have demonstrated that lower densities are associated with less postinflammatory hyperpigmentation in Asian and Black patients, without sacrificing clinical outcomes. “Density determines how ‘aggressive’ a treatment is,” he said. “The greater the density, the more downtime is required.”

8. Have a vascular occlusion emergency kit on hand. At a minimum, the kit should contain at least 1,500 units of hyaluronidase, aspirin, timolol/acetazolamide, a Snellen chart, steroids, and an EpiPen.

9. Use standardized photography. Even the slightest change in lighting can manipulate your results. According to Dr. Jalian, standardized photos enable you to monitor patient progress, minimize liability, and can serve as a marketing tool “so that you can capitalize on your talent.”

10. Consider combination treatments. He combines lasers based on target and depth. For example, prior to resurfacing he often performs a pass or two with a color laser such as intense pulsed light. “Depending on what’s being done, we’ll do soft-tissue augmentation before or after treatment with certain lasers,” Dr. Jalian added. “If you’re performing a toxin treatment on the same day as a laser procedure, do not treat the lower face or neck. Do the laser procedure first and limit that to the upper third of the face.”

He reported having no relevant financial disclosures.

dbrunk@mdedge.com

During the annual conference of the American Society for Laser Medicine and Surgery, H. Ray Jalian, MD, shared his “top 10” tips and tricks for everyday cosmetic practice, based on nearly 10 years of experience treating patients on both coasts of the United States.

They are as follows:

1. Know your clinical endpoints. “One of the things that was drilled into me during my fellowship in lasers and cosmetics at Mass General was to know your clinical endpoints and to avoid a cookbook approach,” said Dr. Jalian, who practices dermatology in Los Angeles. “You should treat based on the pathology that you’re seeing on the skin and let the endpoints be your guide. The skin will tell you what you’re doing right, and the skin will tell you what you’re doing wrong. Picking up on these cues will allow you to deliver a safe and effective treatment to your patients.”

The selection of proper treatment parameters is driven by selective photothermolysis, a microsurgery technique that uses customized wavelengths, pulse durations, and fluences to target a chromophore. “Knowing the size and shape of your target allows you to pick the right pulse duration,” he said. “This is dictated by thermal relaxation time, which is proportional to the size and shape of the target. Smaller targets require a shorter pulse width, while larger targets require a longer pulse width.”

2. Do not perform a procedure for which you cannot recognize and treat the side effects. “I can’t tell you how many times I’ve gotten referrals from outside providers with a side effect that, if it had been recognized and treated, would have been inconsequential long-term for the patient,” Dr. Jalian said. “You can only avoid complications by not firing the laser. The more you practice, the more complications you’re going to have. This is inevitable, but good practice and common sense can reduce complications significantly.”

Even the most skilled clinicians encounter side effects from time to time. “The most important thing is to form a network of physicians you trust that you can call or text when you need help in managing a particular complication,” he continued. “This happens to all of us,” he said. Don’t be afraid to phone a colleague, he advised, “and get a fresh set of eyes because oftentimes they can provide insights, especially when you’re having tunnel vision during a complication, that can ultimately result in better patient care.”

3. Don’t forget your clinical training. “Trust your clinical judgment,” Dr. Jalian said. “If something doesn’t seem right, even if it was a case referred to you by experienced practitioners, you are a clinician first and foremost, and you are allowed to make a clinical judgment on lesions.” He referred to a 2011 report in which the authors described a series of four cases where patients presented for cosmetic evaluation of vascular lesions that turned out to be more significant pathologic disease. “Trust your clinical insight because this will serve you in the long term,” he said.

4. Set realistic expectations. Patients with unrealistically high expectations are likely to express dissatisfaction with their treatment results, “no matter how good of a job you do,” Dr. Jalian said. “In addition to safely treating the patient, we strive for patient satisfaction, because with these elective procedures we’re trying to give a patient a result they’re looking for. But our No. 1 job is also to be realistic about the results we can obtain. If someone comes in wanting treatment with a skin-tightening device but clearly needs a face-lift because they have too much laxity, your job is to tell them that this is not the appropriate device for them. Learn the art of saying no. If handled correctly, the patient will often thank you before she heads out the door. Ultimately, honesty is the best policy. I may say something like, ‘I’m not telling you the answer you want to hear, I’m telling you the truth.’ That often goes over well.”

5. Use proper anesthesia. Patients come to you for results, but they’re also likely to remember how well you controlled their pain during procedures. Strategies favored by Dr. Jalian include applying extra topical anesthetic to “hot spots” and splitting up treatment sessions when tackling a large area. “Consider using adjunctive analgesics such as oral medications and nitrous oxide,” he added. Other options, he said, are cooling techniques and distraction techniques, such as the use of a stress ball, consideration of the gate control theory of pain, and “talkesthesia”(using conversation to distract the patient).

6. Obtain proper informed consent. A lack of informed consent ranks as a common reason why doctors get sued. “This happens when a physician fails to inform the patient of all medically reasonable alternatives and their risks, even for noninvasive procedures prior to administering treatment,” Dr. Jalian said. “All patients have the right to an informed consent prior to any treatment. It doesn’t necessarily have to be in a written form, but it’s important to at least have a discussion and document it for all procedures, including medical and cosmetic procedures and oral and topical treatments. Keep it simple. A written consent is ineffective if the patient does not understand material about the procedure.” Avoid the use of excessive medical terms. For example, use bruising instead of purpura, redness instead of erythema, and drooping instead of ptosis.

7. Lower the laser treatment density for darker skin types. According to Dr. Jalian, several clinical studies have demonstrated that lower densities are associated with less postinflammatory hyperpigmentation in Asian and Black patients, without sacrificing clinical outcomes. “Density determines how ‘aggressive’ a treatment is,” he said. “The greater the density, the more downtime is required.”

8. Have a vascular occlusion emergency kit on hand. At a minimum, the kit should contain at least 1,500 units of hyaluronidase, aspirin, timolol/acetazolamide, a Snellen chart, steroids, and an EpiPen.

9. Use standardized photography. Even the slightest change in lighting can manipulate your results. According to Dr. Jalian, standardized photos enable you to monitor patient progress, minimize liability, and can serve as a marketing tool “so that you can capitalize on your talent.”

10. Consider combination treatments. He combines lasers based on target and depth. For example, prior to resurfacing he often performs a pass or two with a color laser such as intense pulsed light. “Depending on what’s being done, we’ll do soft-tissue augmentation before or after treatment with certain lasers,” Dr. Jalian added. “If you’re performing a toxin treatment on the same day as a laser procedure, do not treat the lower face or neck. Do the laser procedure first and limit that to the upper third of the face.”

He reported having no relevant financial disclosures.

dbrunk@mdedge.com

During the annual conference of the American Society for Laser Medicine and Surgery, H. Ray Jalian, MD, shared his “top 10” tips and tricks for everyday cosmetic practice, based on nearly 10 years of experience treating patients on both coasts of the United States.

They are as follows:

1. Know your clinical endpoints. “One of the things that was drilled into me during my fellowship in lasers and cosmetics at Mass General was to know your clinical endpoints and to avoid a cookbook approach,” said Dr. Jalian, who practices dermatology in Los Angeles. “You should treat based on the pathology that you’re seeing on the skin and let the endpoints be your guide. The skin will tell you what you’re doing right, and the skin will tell you what you’re doing wrong. Picking up on these cues will allow you to deliver a safe and effective treatment to your patients.”

The selection of proper treatment parameters is driven by selective photothermolysis, a microsurgery technique that uses customized wavelengths, pulse durations, and fluences to target a chromophore. “Knowing the size and shape of your target allows you to pick the right pulse duration,” he said. “This is dictated by thermal relaxation time, which is proportional to the size and shape of the target. Smaller targets require a shorter pulse width, while larger targets require a longer pulse width.”

2. Do not perform a procedure for which you cannot recognize and treat the side effects. “I can’t tell you how many times I’ve gotten referrals from outside providers with a side effect that, if it had been recognized and treated, would have been inconsequential long-term for the patient,” Dr. Jalian said. “You can only avoid complications by not firing the laser. The more you practice, the more complications you’re going to have. This is inevitable, but good practice and common sense can reduce complications significantly.”

Even the most skilled clinicians encounter side effects from time to time. “The most important thing is to form a network of physicians you trust that you can call or text when you need help in managing a particular complication,” he continued. “This happens to all of us,” he said. Don’t be afraid to phone a colleague, he advised, “and get a fresh set of eyes because oftentimes they can provide insights, especially when you’re having tunnel vision during a complication, that can ultimately result in better patient care.”

3. Don’t forget your clinical training. “Trust your clinical judgment,” Dr. Jalian said. “If something doesn’t seem right, even if it was a case referred to you by experienced practitioners, you are a clinician first and foremost, and you are allowed to make a clinical judgment on lesions.” He referred to a 2011 report in which the authors described a series of four cases where patients presented for cosmetic evaluation of vascular lesions that turned out to be more significant pathologic disease. “Trust your clinical insight because this will serve you in the long term,” he said.

4. Set realistic expectations. Patients with unrealistically high expectations are likely to express dissatisfaction with their treatment results, “no matter how good of a job you do,” Dr. Jalian said. “In addition to safely treating the patient, we strive for patient satisfaction, because with these elective procedures we’re trying to give a patient a result they’re looking for. But our No. 1 job is also to be realistic about the results we can obtain. If someone comes in wanting treatment with a skin-tightening device but clearly needs a face-lift because they have too much laxity, your job is to tell them that this is not the appropriate device for them. Learn the art of saying no. If handled correctly, the patient will often thank you before she heads out the door. Ultimately, honesty is the best policy. I may say something like, ‘I’m not telling you the answer you want to hear, I’m telling you the truth.’ That often goes over well.”

5. Use proper anesthesia. Patients come to you for results, but they’re also likely to remember how well you controlled their pain during procedures. Strategies favored by Dr. Jalian include applying extra topical anesthetic to “hot spots” and splitting up treatment sessions when tackling a large area. “Consider using adjunctive analgesics such as oral medications and nitrous oxide,” he added. Other options, he said, are cooling techniques and distraction techniques, such as the use of a stress ball, consideration of the gate control theory of pain, and “talkesthesia”(using conversation to distract the patient).

6. Obtain proper informed consent. A lack of informed consent ranks as a common reason why doctors get sued. “This happens when a physician fails to inform the patient of all medically reasonable alternatives and their risks, even for noninvasive procedures prior to administering treatment,” Dr. Jalian said. “All patients have the right to an informed consent prior to any treatment. It doesn’t necessarily have to be in a written form, but it’s important to at least have a discussion and document it for all procedures, including medical and cosmetic procedures and oral and topical treatments. Keep it simple. A written consent is ineffective if the patient does not understand material about the procedure.” Avoid the use of excessive medical terms. For example, use bruising instead of purpura, redness instead of erythema, and drooping instead of ptosis.

7. Lower the laser treatment density for darker skin types. According to Dr. Jalian, several clinical studies have demonstrated that lower densities are associated with less postinflammatory hyperpigmentation in Asian and Black patients, without sacrificing clinical outcomes. “Density determines how ‘aggressive’ a treatment is,” he said. “The greater the density, the more downtime is required.”

8. Have a vascular occlusion emergency kit on hand. At a minimum, the kit should contain at least 1,500 units of hyaluronidase, aspirin, timolol/acetazolamide, a Snellen chart, steroids, and an EpiPen.

9. Use standardized photography. Even the slightest change in lighting can manipulate your results. According to Dr. Jalian, standardized photos enable you to monitor patient progress, minimize liability, and can serve as a marketing tool “so that you can capitalize on your talent.”

10. Consider combination treatments. He combines lasers based on target and depth. For example, prior to resurfacing he often performs a pass or two with a color laser such as intense pulsed light. “Depending on what’s being done, we’ll do soft-tissue augmentation before or after treatment with certain lasers,” Dr. Jalian added. “If you’re performing a toxin treatment on the same day as a laser procedure, do not treat the lower face or neck. Do the laser procedure first and limit that to the upper third of the face.”

He reported having no relevant financial disclosures.

dbrunk@mdedge.com

The way Kelly Stankiewicz, MD, sees it, the first step in any cosmetic consultation is to be present and listen intently to the patient’s concerns.

“I can’t tell you how many times I’ve walked into a room and thought the patient would say they’re concerned about one thing, but they’re concerned about something totally different,” Dr. Stankiewicz, a dermatologist in private practice in Park City, Utah, said during the annual conference of the American Society for Laser Medicine and Surgery. “The first question I ask is, ‘What would you like to improve?’ ‘What’s bothering you?’ ‘What would you like to make look better?’ Frequently, it’s not what you think.”

Next, she tries to get a sense of their lifestyle by asking patients about their occupation, hobbies, and outdoor activities they may engage in. “Here in Park City, it’s very sunny most all the time, so treatments need to be tailored to when those outdoor activities are being done, or perhaps they can be avoided for a period of time,” she said. “This gives you an idea of what kind of downtime people will tolerate. I also like to hear about their history of cosmetic procedures. If someone has had a lot of cosmetic procedures done, you can talk with them on a more detailed level. If someone is completely unaware of treatment options, you have to keep it simple.”

Dr. Stankiewicz also reviews their personal history of cosmetic procedures when considering safety of treatment. “For instance, if somebody has had a neck lift, you want to be very cautious doing any ablative procedures along the jawline,” she said. “I also like to know if anyone has had any reactions to dermal fillers or neuromodulators that they did not like. It’s very helpful to hear from patients what’s worked for them and what hasn’t. I also like to keep my ear open for pricing concerns. Not everyone will bring up the pricing issues, but sometimes they will, and it’s an important piece of information. Lastly, it’s important to look for any warning signs like irrational behavior or unrealistic expectations. These are patients you want to try to avoid treating.”

She shared four other key components to an effective cosmetic consultation, including the examination itself, which she prefers to separate from the discussion portion of the visit. “I lean the patient back in the exam chair and shine the light on their skin, which is important for evaluating for conditions you may not have discussed that could be easily improved,” Dr. Stankiewicz said.

“If the patient is concerned about pigmented lesions, I’ll pull out my dermatoscope to make sure there isn’t any concern for skin cancer. After the examination, I’ll sit the patient up again so that there is a very distinct start and finish to the examination portion of my cosmetic consultation.”

Surgery vs. noninvasive treatments

Step three in her consultative process is to review treatment options with patients. “I never hold back if surgery is their best treatment option,” she said. “I don’t perform surgery, but I have a list of people I can refer them to.”

CasarsaGuru/Getty Images

Once she addresses the potential for surgery, she reviews noninvasive treatment options, including topical products, injectables, lasers, and chemical peels. “Everyone who comes in for a cosmetic consultation leaves with some sort of topical recommendation, even if it’s as simple as a sunscreen I think they would like or a prescription for generic tretinoin,” she said. “I always present options in a framework starting with those that require lower downtime, higher number of treatment options, and lower cost. Then I move up the scale to tell them more about treatments that require higher downtime, a lower number of treatments, but have a higher cost.”

Step four in her consultative process involves discussing her final treatment recommendations. She’ll say something like, “I’ve been through all these options with you and my final recommendation is X,” and the patient walks away with a clear understanding of the recommendations, she said. “When I leave the room after giving my final recommendation, I’ll write everything down outside of the room, or I’ll have a member of my staff write down everything I’ve said outside the room.”

Finally, she and her staff record all the relevant information for the patient as a customized handout, including the treatment options discussed, how many will be required, whether they have to come in early for numbing cream or not, and the per treatment price tag. “Once we’ve written down everything we’ve discussed, I’ll circle or I’ll star my recommended treatment,” Dr. Stankiewicz said. They also have a handout for topical products, and she checks off the topical products that she discussed with the patient. The third handout she provides to patients is a recommended skin care regimen.

Dr. Stankiewicz reported having no relevant financial disclosures.

dbrunk@mdedge.com

The way Kelly Stankiewicz, MD, sees it, the first step in any cosmetic consultation is to be present and listen intently to the patient’s concerns.

“I can’t tell you how many times I’ve walked into a room and thought the patient would say they’re concerned about one thing, but they’re concerned about something totally different,” Dr. Stankiewicz, a dermatologist in private practice in Park City, Utah, said during the annual conference of the American Society for Laser Medicine and Surgery. “The first question I ask is, ‘What would you like to improve?’ ‘What’s bothering you?’ ‘What would you like to make look better?’ Frequently, it’s not what you think.”

Next, she tries to get a sense of their lifestyle by asking patients about their occupation, hobbies, and outdoor activities they may engage in. “Here in Park City, it’s very sunny most all the time, so treatments need to be tailored to when those outdoor activities are being done, or perhaps they can be avoided for a period of time,” she said. “This gives you an idea of what kind of downtime people will tolerate. I also like to hear about their history of cosmetic procedures. If someone has had a lot of cosmetic procedures done, you can talk with them on a more detailed level. If someone is completely unaware of treatment options, you have to keep it simple.”

Dr. Stankiewicz also reviews their personal history of cosmetic procedures when considering safety of treatment. “For instance, if somebody has had a neck lift, you want to be very cautious doing any ablative procedures along the jawline,” she said. “I also like to know if anyone has had any reactions to dermal fillers or neuromodulators that they did not like. It’s very helpful to hear from patients what’s worked for them and what hasn’t. I also like to keep my ear open for pricing concerns. Not everyone will bring up the pricing issues, but sometimes they will, and it’s an important piece of information. Lastly, it’s important to look for any warning signs like irrational behavior or unrealistic expectations. These are patients you want to try to avoid treating.”

She shared four other key components to an effective cosmetic consultation, including the examination itself, which she prefers to separate from the discussion portion of the visit. “I lean the patient back in the exam chair and shine the light on their skin, which is important for evaluating for conditions you may not have discussed that could be easily improved,” Dr. Stankiewicz said.

“If the patient is concerned about pigmented lesions, I’ll pull out my dermatoscope to make sure there isn’t any concern for skin cancer. After the examination, I’ll sit the patient up again so that there is a very distinct start and finish to the examination portion of my cosmetic consultation.”

Surgery vs. noninvasive treatments

Step three in her consultative process is to review treatment options with patients. “I never hold back if surgery is their best treatment option,” she said. “I don’t perform surgery, but I have a list of people I can refer them to.”

CasarsaGuru/Getty Images

Once she addresses the potential for surgery, she reviews noninvasive treatment options, including topical products, injectables, lasers, and chemical peels. “Everyone who comes in for a cosmetic consultation leaves with some sort of topical recommendation, even if it’s as simple as a sunscreen I think they would like or a prescription for generic tretinoin,” she said. “I always present options in a framework starting with those that require lower downtime, higher number of treatment options, and lower cost. Then I move up the scale to tell them more about treatments that require higher downtime, a lower number of treatments, but have a higher cost.”

Step four in her consultative process involves discussing her final treatment recommendations. She’ll say something like, “I’ve been through all these options with you and my final recommendation is X,” and the patient walks away with a clear understanding of the recommendations, she said. “When I leave the room after giving my final recommendation, I’ll write everything down outside of the room, or I’ll have a member of my staff write down everything I’ve said outside the room.”

Finally, she and her staff record all the relevant information for the patient as a customized handout, including the treatment options discussed, how many will be required, whether they have to come in early for numbing cream or not, and the per treatment price tag. “Once we’ve written down everything we’ve discussed, I’ll circle or I’ll star my recommended treatment,” Dr. Stankiewicz said. They also have a handout for topical products, and she checks off the topical products that she discussed with the patient. The third handout she provides to patients is a recommended skin care regimen.

Dr. Stankiewicz reported having no relevant financial disclosures.

dbrunk@mdedge.com

The way Kelly Stankiewicz, MD, sees it, the first step in any cosmetic consultation is to be present and listen intently to the patient’s concerns.

“I can’t tell you how many times I’ve walked into a room and thought the patient would say they’re concerned about one thing, but they’re concerned about something totally different,” Dr. Stankiewicz, a dermatologist in private practice in Park City, Utah, said during the annual conference of the American Society for Laser Medicine and Surgery. “The first question I ask is, ‘What would you like to improve?’ ‘What’s bothering you?’ ‘What would you like to make look better?’ Frequently, it’s not what you think.”

Next, she tries to get a sense of their lifestyle by asking patients about their occupation, hobbies, and outdoor activities they may engage in. “Here in Park City, it’s very sunny most all the time, so treatments need to be tailored to when those outdoor activities are being done, or perhaps they can be avoided for a period of time,” she said. “This gives you an idea of what kind of downtime people will tolerate. I also like to hear about their history of cosmetic procedures. If someone has had a lot of cosmetic procedures done, you can talk with them on a more detailed level. If someone is completely unaware of treatment options, you have to keep it simple.”

Dr. Stankiewicz also reviews their personal history of cosmetic procedures when considering safety of treatment. “For instance, if somebody has had a neck lift, you want to be very cautious doing any ablative procedures along the jawline,” she said. “I also like to know if anyone has had any reactions to dermal fillers or neuromodulators that they did not like. It’s very helpful to hear from patients what’s worked for them and what hasn’t. I also like to keep my ear open for pricing concerns. Not everyone will bring up the pricing issues, but sometimes they will, and it’s an important piece of information. Lastly, it’s important to look for any warning signs like irrational behavior or unrealistic expectations. These are patients you want to try to avoid treating.”

She shared four other key components to an effective cosmetic consultation, including the examination itself, which she prefers to separate from the discussion portion of the visit. “I lean the patient back in the exam chair and shine the light on their skin, which is important for evaluating for conditions you may not have discussed that could be easily improved,” Dr. Stankiewicz said.

“If the patient is concerned about pigmented lesions, I’ll pull out my dermatoscope to make sure there isn’t any concern for skin cancer. After the examination, I’ll sit the patient up again so that there is a very distinct start and finish to the examination portion of my cosmetic consultation.”

Surgery vs. noninvasive treatments

Step three in her consultative process is to review treatment options with patients. “I never hold back if surgery is their best treatment option,” she said. “I don’t perform surgery, but I have a list of people I can refer them to.”

CasarsaGuru/Getty Images

Once she addresses the potential for surgery, she reviews noninvasive treatment options, including topical products, injectables, lasers, and chemical peels. “Everyone who comes in for a cosmetic consultation leaves with some sort of topical recommendation, even if it’s as simple as a sunscreen I think they would like or a prescription for generic tretinoin,” she said. “I always present options in a framework starting with those that require lower downtime, higher number of treatment options, and lower cost. Then I move up the scale to tell them more about treatments that require higher downtime, a lower number of treatments, but have a higher cost.”

Step four in her consultative process involves discussing her final treatment recommendations. She’ll say something like, “I’ve been through all these options with you and my final recommendation is X,” and the patient walks away with a clear understanding of the recommendations, she said. “When I leave the room after giving my final recommendation, I’ll write everything down outside of the room, or I’ll have a member of my staff write down everything I’ve said outside the room.”

Finally, she and her staff record all the relevant information for the patient as a customized handout, including the treatment options discussed, how many will be required, whether they have to come in early for numbing cream or not, and the per treatment price tag. “Once we’ve written down everything we’ve discussed, I’ll circle or I’ll star my recommended treatment,” Dr. Stankiewicz said. They also have a handout for topical products, and she checks off the topical products that she discussed with the patient. The third handout she provides to patients is a recommended skin care regimen.

Dr. Stankiewicz reported having no relevant financial disclosures.

dbrunk@mdedge.com

A 2,940-nm and 1,470-nm hybrid fractional laser was found to be safe and effective for treating the genitourinary syndrome of menopause (GSM), results from a pilot trial showed.

“The genitourinary syndrome of menopause causes suffering in breast cancer survivors and postmenopausal women,” Jill S. Waibel, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. A common side effect for breast cancer survivors is early onset of menopause that is brought on by treatment, specifically aromatase-inhibitor therapies, she noted.

The symptoms of GSM include discomfort during sex, impaired sexual function, burning or sensation or irritation of the genital area, vaginal constriction, frequent urinary tract infections, urinary incontinence, and vaginal laxity, said Dr. Waibel, owner and medical director of the Miami Dermatology and Laser Institute. Nonhormonal treatments have included OTC vaginal lubricants, OTC moisturizers, low-dose vaginal estrogen – which increases the risk of breast cancer – and systemic estrogen therapy, which also can increase the risk of breast and endometrial cancer. “So, we need a healthy, nondrug option,” she said.

The objective of the pilot study was to determine the safety and efficacy of the diVa hybrid fractional laser as a treatment for symptoms of genitourinary syndrome of menopause, early menopause after breast cancer, or vaginal atrophy. The laser applies tunable nonablative (1,470-nm) and ablative (2,940-nm) wavelengths to the same microscopic treatment zone to maximize results and reduce downtime. The device features a motorized precision guidance system and calibrated rotation for homogeneous pulsing.

“The 2,940-nm wavelength is used to ablate to a depth of 0-800 micrometers while the 1,470-nm wavelength is used to coagulate the epithelium and the lamina propria at a depth of 100-700 micrometers,” said Dr. Waibel, who is also subsection chief of dermatology at Baptist Hospital of Miami. “This combination is used for epithelial tissue to heal quickly and the lamina propria to remodel slowly over time, laying down more collagen in tissue.” Each procedure is delivered via a single-use dilator, which expands the vaginal canal for increased treatment area. “The tip length is 5.5 cm and the diameter is 1 cm,” she said. “The clear tip acts as a hygienic barrier between the tip and the handpiece.”

Study participants included 25 women between the ages of 40 and 70 with early menopause after breast cancer or vaginal atrophy: 20 in the treatment arm and 5 in the sham-treatment arm. Dr. Waibel performed three procedures 2 weeks apart. An ob.gyn. assessed the primary endpoints, which included the Vaginal Health Index Scale (VHIS), the Vaginal Maturation Index (VMI), the Female Sexual Function Index (FSFI) questionnaire, and the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire. Secondary endpoints were histology and a satisfaction questionnaire.

Of the women in the treated group, there were data available for 19 at 3 months follow-up and 17 at 6 months follow-up. Based on the results in these patients, there were statistically significant improvements in nearly all domains of the FSFI treatment arm at 3 and 6 months when compared to baseline, especially arousal (P values of .05 at 3 months and .01 at 6 months) and lubrication (P values of .009 at three months and .001 at 6 months).

Between 3 and 6 months, patients in the treatment arm experienced improvements in four dimensions of the DIVA questionnaire: daily activities (P value of .01 at 3 months to .010 at 6 months), emotional well-being (P value of .06 at 3 months to .014 at 6 months), sexual function (P value of .30 at 3 months to .003 at 6 months), and self-concept/body image (P value of .002 at 3 months to .001 at 6 months).

As for satisfaction, a majority of those in the treatment arm were “somewhat satisfied” with the treatment and would “somewhat likely” repeat and recommend the treatment to friends and family, Dr. Waibel said. Results among the women in the control arm, who were also surveyed, were in the similar range, she noted. (No other results for women in the control arm were available.)

Following treatments, histology revealed that the collagen was denser, fibroblasts were more dense, and vascularity was more notable. No adverse events were observed. “The hybrid fractional laser is safe and effective for treating GSM, early menopause after breast cancer, or vaginal atrophy,” Dr. Waibel concluded. Further studies are important to improve the understanding of “laser dosimetry, frequency of treatments, and longevity of effect. Collaboration between ob.gyns. and dermatologists is important as we learn about laser therapy in GSM.”

Dr. Waibel disclosed that she is a member of the advisory board of Sciton, which manufactures the diVa laser. She has also conducted clinical trials for many other device and pharmaceutical companies.

dbrunk@mdedge.com

A 2,940-nm and 1,470-nm hybrid fractional laser was found to be safe and effective for treating the genitourinary syndrome of menopause (GSM), results from a pilot trial showed.

“The genitourinary syndrome of menopause causes suffering in breast cancer survivors and postmenopausal women,” Jill S. Waibel, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. A common side effect for breast cancer survivors is early onset of menopause that is brought on by treatment, specifically aromatase-inhibitor therapies, she noted.

The symptoms of GSM include discomfort during sex, impaired sexual function, burning or sensation or irritation of the genital area, vaginal constriction, frequent urinary tract infections, urinary incontinence, and vaginal laxity, said Dr. Waibel, owner and medical director of the Miami Dermatology and Laser Institute. Nonhormonal treatments have included OTC vaginal lubricants, OTC moisturizers, low-dose vaginal estrogen – which increases the risk of breast cancer – and systemic estrogen therapy, which also can increase the risk of breast and endometrial cancer. “So, we need a healthy, nondrug option,” she said.

The objective of the pilot study was to determine the safety and efficacy of the diVa hybrid fractional laser as a treatment for symptoms of genitourinary syndrome of menopause, early menopause after breast cancer, or vaginal atrophy. The laser applies tunable nonablative (1,470-nm) and ablative (2,940-nm) wavelengths to the same microscopic treatment zone to maximize results and reduce downtime. The device features a motorized precision guidance system and calibrated rotation for homogeneous pulsing.

“The 2,940-nm wavelength is used to ablate to a depth of 0-800 micrometers while the 1,470-nm wavelength is used to coagulate the epithelium and the lamina propria at a depth of 100-700 micrometers,” said Dr. Waibel, who is also subsection chief of dermatology at Baptist Hospital of Miami. “This combination is used for epithelial tissue to heal quickly and the lamina propria to remodel slowly over time, laying down more collagen in tissue.” Each procedure is delivered via a single-use dilator, which expands the vaginal canal for increased treatment area. “The tip length is 5.5 cm and the diameter is 1 cm,” she said. “The clear tip acts as a hygienic barrier between the tip and the handpiece.”

Study participants included 25 women between the ages of 40 and 70 with early menopause after breast cancer or vaginal atrophy: 20 in the treatment arm and 5 in the sham-treatment arm. Dr. Waibel performed three procedures 2 weeks apart. An ob.gyn. assessed the primary endpoints, which included the Vaginal Health Index Scale (VHIS), the Vaginal Maturation Index (VMI), the Female Sexual Function Index (FSFI) questionnaire, and the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire. Secondary endpoints were histology and a satisfaction questionnaire.

Of the women in the treated group, there were data available for 19 at 3 months follow-up and 17 at 6 months follow-up. Based on the results in these patients, there were statistically significant improvements in nearly all domains of the FSFI treatment arm at 3 and 6 months when compared to baseline, especially arousal (P values of .05 at 3 months and .01 at 6 months) and lubrication (P values of .009 at three months and .001 at 6 months).

Between 3 and 6 months, patients in the treatment arm experienced improvements in four dimensions of the DIVA questionnaire: daily activities (P value of .01 at 3 months to .010 at 6 months), emotional well-being (P value of .06 at 3 months to .014 at 6 months), sexual function (P value of .30 at 3 months to .003 at 6 months), and self-concept/body image (P value of .002 at 3 months to .001 at 6 months).

As for satisfaction, a majority of those in the treatment arm were “somewhat satisfied” with the treatment and would “somewhat likely” repeat and recommend the treatment to friends and family, Dr. Waibel said. Results among the women in the control arm, who were also surveyed, were in the similar range, she noted. (No other results for women in the control arm were available.)

Following treatments, histology revealed that the collagen was denser, fibroblasts were more dense, and vascularity was more notable. No adverse events were observed. “The hybrid fractional laser is safe and effective for treating GSM, early menopause after breast cancer, or vaginal atrophy,” Dr. Waibel concluded. Further studies are important to improve the understanding of “laser dosimetry, frequency of treatments, and longevity of effect. Collaboration between ob.gyns. and dermatologists is important as we learn about laser therapy in GSM.”

Dr. Waibel disclosed that she is a member of the advisory board of Sciton, which manufactures the diVa laser. She has also conducted clinical trials for many other device and pharmaceutical companies.

dbrunk@mdedge.com

A 2,940-nm and 1,470-nm hybrid fractional laser was found to be safe and effective for treating the genitourinary syndrome of menopause (GSM), results from a pilot trial showed.

“The genitourinary syndrome of menopause causes suffering in breast cancer survivors and postmenopausal women,” Jill S. Waibel, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. A common side effect for breast cancer survivors is early onset of menopause that is brought on by treatment, specifically aromatase-inhibitor therapies, she noted.

The symptoms of GSM include discomfort during sex, impaired sexual function, burning or sensation or irritation of the genital area, vaginal constriction, frequent urinary tract infections, urinary incontinence, and vaginal laxity, said Dr. Waibel, owner and medical director of the Miami Dermatology and Laser Institute. Nonhormonal treatments have included OTC vaginal lubricants, OTC moisturizers, low-dose vaginal estrogen – which increases the risk of breast cancer – and systemic estrogen therapy, which also can increase the risk of breast and endometrial cancer. “So, we need a healthy, nondrug option,” she said.

The objective of the pilot study was to determine the safety and efficacy of the diVa hybrid fractional laser as a treatment for symptoms of genitourinary syndrome of menopause, early menopause after breast cancer, or vaginal atrophy. The laser applies tunable nonablative (1,470-nm) and ablative (2,940-nm) wavelengths to the same microscopic treatment zone to maximize results and reduce downtime. The device features a motorized precision guidance system and calibrated rotation for homogeneous pulsing.

“The 2,940-nm wavelength is used to ablate to a depth of 0-800 micrometers while the 1,470-nm wavelength is used to coagulate the epithelium and the lamina propria at a depth of 100-700 micrometers,” said Dr. Waibel, who is also subsection chief of dermatology at Baptist Hospital of Miami. “This combination is used for epithelial tissue to heal quickly and the lamina propria to remodel slowly over time, laying down more collagen in tissue.” Each procedure is delivered via a single-use dilator, which expands the vaginal canal for increased treatment area. “The tip length is 5.5 cm and the diameter is 1 cm,” she said. “The clear tip acts as a hygienic barrier between the tip and the handpiece.”

Study participants included 25 women between the ages of 40 and 70 with early menopause after breast cancer or vaginal atrophy: 20 in the treatment arm and 5 in the sham-treatment arm. Dr. Waibel performed three procedures 2 weeks apart. An ob.gyn. assessed the primary endpoints, which included the Vaginal Health Index Scale (VHIS), the Vaginal Maturation Index (VMI), the Female Sexual Function Index (FSFI) questionnaire, and the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire. Secondary endpoints were histology and a satisfaction questionnaire.

Of the women in the treated group, there were data available for 19 at 3 months follow-up and 17 at 6 months follow-up. Based on the results in these patients, there were statistically significant improvements in nearly all domains of the FSFI treatment arm at 3 and 6 months when compared to baseline, especially arousal (P values of .05 at 3 months and .01 at 6 months) and lubrication (P values of .009 at three months and .001 at 6 months).

Between 3 and 6 months, patients in the treatment arm experienced improvements in four dimensions of the DIVA questionnaire: daily activities (P value of .01 at 3 months to .010 at 6 months), emotional well-being (P value of .06 at 3 months to .014 at 6 months), sexual function (P value of .30 at 3 months to .003 at 6 months), and self-concept/body image (P value of .002 at 3 months to .001 at 6 months).

As for satisfaction, a majority of those in the treatment arm were “somewhat satisfied” with the treatment and would “somewhat likely” repeat and recommend the treatment to friends and family, Dr. Waibel said. Results among the women in the control arm, who were also surveyed, were in the similar range, she noted. (No other results for women in the control arm were available.)

Following treatments, histology revealed that the collagen was denser, fibroblasts were more dense, and vascularity was more notable. No adverse events were observed. “The hybrid fractional laser is safe and effective for treating GSM, early menopause after breast cancer, or vaginal atrophy,” Dr. Waibel concluded. Further studies are important to improve the understanding of “laser dosimetry, frequency of treatments, and longevity of effect. Collaboration between ob.gyns. and dermatologists is important as we learn about laser therapy in GSM.”

Dr. Waibel disclosed that she is a member of the advisory board of Sciton, which manufactures the diVa laser. She has also conducted clinical trials for many other device and pharmaceutical companies.

dbrunk@mdedge.com