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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
PD-1 inhibitor improves outcomes in NHL subtype
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
FROM ESMO 2023
Phase 3 trial supports topical JAK inhibitor for AD in young children
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
AT THE EADV CONGRESS
Drug-eluting resorbable scaffold beats angioplasty for infrapopliteal artery disease
SAN FRANCISCO – An everolimus-eluting stent with a resorbable scaffold showed superior efficacy in a randomized multicenter trial when compared with angioplasty for the treatment of patients with chronic limb threatening ischemia (CLTI) resulting from infrapopliteal artery disease.
The stent (Esprit BTK, Abbott Vascular) was also noninferior to angioplasty in terms of safety.
Presenting results of the LIFE-BTK trial at the Transcatheter Cardiovascular Therapeutics annual meeting, Ramon Varcoe, MBBS, MS, PhD, MMed, of Prince of Wales Hospital, Sydney, said that peripheral artery disease is a global epidemic, the most serious manifestation of which is CTLI.
“If not treated expeditiously, this could lead to high rates of amputation, which, as we all know, has a severe impact on patients’ quality of life and even worse impact on their life prognosis, with prognosis rates worse than most cancers.”
He said that for infrapopliteal or below-the-knee (BTK) arterial disease, treatment with angioplasty has proven superior to bypass graft surgery, but some limitations of angioplasty are elastic recoil, dissection, and restenosis, thus limiting its durability. Coronary drug-eluting stents showed promise in BTK procedures but can interfere with reintervention. Thus, LIFE-BTK compared a drug-eluting stent with resorbable scaffolding to surgery.
Esprit BTK is a drug-eluting resorbable scaffold consisting of a temporary scaffold backbone of poly(L-lactide) and a strut thickness of 99 μm. It is coated with everolimus and bioresorbable poly(D,L-lactide). Two platinum markers at each end provide radiopacity.
LIFE-BTK enrolled patients aged 18 years or older with CLTI associated with ischemic rest pain or minor tissue loss and who had infrapopliteal artery stenosis or occlusion. The trial was prospective, international multicenter, and single-blind and randomly assigned 261 patients aged 18 years or older in the ratio of 2:1 to Esprit BTK (n = 173) or to angioplasty (n = 88). Treatment of up to two target lesions was allowed with a total scaffold length less than 170 mm.
The primary efficacy endpoint was superiority of Esprit BTK over angioplasty in terms of freedom of above-ankle amputation in the index limb, binary restenosis of the target lesion, and clinically driven target lesion revascularization evaluated at 1 year.
The primary safety endpoint, evaluated at 6 months, consisted of freedom from above-ankle amputation, major reintervention at 6 months, and perioperative mortality at 30 days.
An independent committee adjudicated clinical events, and core laboratories with assessors blinded to trial group assignment adjudicated imaging results and wound assessments.
Superior efficacy, noninferior safety
Participants were about two-thirds men, largely White, with about 15% of participants being Black/African American, and more than 90% of patients in each arm had hypertension. Lesion lengths were approximately 44 mm in each group with reference vessel diameters averaging 2.82-2.94 mm before intervention. Less than 4% in each group had severe lesion calcification.
Clinical follow-up rate at 1 year in the Esprit BTK arm was 90.2% and in the angioplasty arm 90.9%. Six patients in the former arm died versus five in the latter.
At the meeting, sponsored by the Cardiovascular Research Foundation, Dr. Varcoe showed a graph of the primary efficacy results at 453 days, the extra time being allowed to achieve a diagnostic ultrasound. (P < .0001).
“As you can see, those bars start to diverge in about 5 months and continue to separate over time, showing clear superiority of the scaffold over angioplasty, absolute risk difference of 30.8% and a highly statistically significant P value,” he said. Very similar primary efficacy outcomes were seen at 393 days.
At 1 year, the secondary efficacy endpoint of binary restenosis of the target lesion occurred in 24.2% of scaffold patients versus 46.5% of the angioplasty group (P < .0001). Another secondary endpoint, freedom from above-ankle amputation, 100% total occlusion of the target vessel, or clinically driven target lesion revascularization, occurred in 82.5% of the scaffold group versus 70.4% in the angioplasty group (P = .0081).
The primary safety endpoint of freedom from a major adverse limb event plus perioperative death was 100% for angioplasty and 96.9% for Esprit BTK (P = .0019)
All subgroup analyses assessing interaction by sex, race, geographic region, or age showed Esprit BTK was superior to angioplasty, with relative risks ranging from 0.27 to 0.61.
“If this technology is approved by the FDA, it will provide a new option for our patients with very difficult-to-treat disease, which will provide them additional durability and fewer reinterventions,” Dr. Varcoe concluded. “And I think we all know deep down that’s going to translate to improved clinical outcomes and few amputations.”
David Kandzari, MD, of Peidmont Heart Institute, Atlanta, was asked to comment on the study. He said that as with other vascular interventions, the ideal technology “would be first to provide a safe and effective antiproliferative therapy that would mitigate against restenosis and for scaffolding to prevent elastic recoil and reocclusion ... and ultimately fulfill these two promises without the requisite of a permanent implant.
“Despite their common use in femoral popliteal disease, drug-coated balloons had at best demonstrated inconsistent results below the knee, and drug-coated balloons, therefore, are not approved for such indications.”
He said that drug-eluting stents have demonstrated efficacy in this indication but that these studies have been limited to fairly discrete proximal disease.
“LIFE-BTK therefore represents one of the most rigorous trials in the space of endovascular interventions as a single line and randomized trial,” Dr. Kandzari said, “showing a primary composite endpoint of both safety and effectiveness relative to conventional angioplasty.”
Dr. Kandzari pointed to strengths of the study in that it used standardization of technique with independent adjudication of both imaging and wound healing assessments. “And the study population, too, was relevant to clinical practice, representing oftentimes underrepresented groups, including those with extensive disease burden [and] clinical severity,” he said. “Importantly, in this study, nearly one-third of the population will be women.”
Panelist Jennifer Rymer, MD, of Duke University Medical Center, Durham, N.C., commented that she treats a lot of African American patients with CTLI and applauded the researchers for including those patients. “I think that this will be a groundbreaking new change in our practice,” she said.
The trial results were published simultaneously with the presentation at TCT 2023 in the New England Journal of Medicine.
Dr. Varcoe reported receiving consulting fees/honoraria from Boston Scientific Corporation, Medtronic, Abbott, BD, Intervene, Surmodics, Philips, Nectero, Alucent, W.L. Gore, Vesteck, Bard Medical, Cook Medical, and R3 Vascular. He has equity, stock, or stock options in EBR Systems and has an executive role or ownership interest in Provisio Medical and Vesteck. Dr. Kandzari received grant support/research contract from Medtronic, Teleflex, Biotronik, and CSI; consultant fees/honoraria from and is on the speaker’s bureau of CSI and Medtronic; and has equity, stock, or options in Biostar Ventures. Dr. Rymer receives grant support/research contract from Chiesi, Abbott Vascular, Abiomed, and Pfizer. The study was funded by Abbott.
A version of this article appeared on Medscape.com.
SAN FRANCISCO – An everolimus-eluting stent with a resorbable scaffold showed superior efficacy in a randomized multicenter trial when compared with angioplasty for the treatment of patients with chronic limb threatening ischemia (CLTI) resulting from infrapopliteal artery disease.
The stent (Esprit BTK, Abbott Vascular) was also noninferior to angioplasty in terms of safety.
Presenting results of the LIFE-BTK trial at the Transcatheter Cardiovascular Therapeutics annual meeting, Ramon Varcoe, MBBS, MS, PhD, MMed, of Prince of Wales Hospital, Sydney, said that peripheral artery disease is a global epidemic, the most serious manifestation of which is CTLI.
“If not treated expeditiously, this could lead to high rates of amputation, which, as we all know, has a severe impact on patients’ quality of life and even worse impact on their life prognosis, with prognosis rates worse than most cancers.”
He said that for infrapopliteal or below-the-knee (BTK) arterial disease, treatment with angioplasty has proven superior to bypass graft surgery, but some limitations of angioplasty are elastic recoil, dissection, and restenosis, thus limiting its durability. Coronary drug-eluting stents showed promise in BTK procedures but can interfere with reintervention. Thus, LIFE-BTK compared a drug-eluting stent with resorbable scaffolding to surgery.
Esprit BTK is a drug-eluting resorbable scaffold consisting of a temporary scaffold backbone of poly(L-lactide) and a strut thickness of 99 μm. It is coated with everolimus and bioresorbable poly(D,L-lactide). Two platinum markers at each end provide radiopacity.
LIFE-BTK enrolled patients aged 18 years or older with CLTI associated with ischemic rest pain or minor tissue loss and who had infrapopliteal artery stenosis or occlusion. The trial was prospective, international multicenter, and single-blind and randomly assigned 261 patients aged 18 years or older in the ratio of 2:1 to Esprit BTK (n = 173) or to angioplasty (n = 88). Treatment of up to two target lesions was allowed with a total scaffold length less than 170 mm.
The primary efficacy endpoint was superiority of Esprit BTK over angioplasty in terms of freedom of above-ankle amputation in the index limb, binary restenosis of the target lesion, and clinically driven target lesion revascularization evaluated at 1 year.
The primary safety endpoint, evaluated at 6 months, consisted of freedom from above-ankle amputation, major reintervention at 6 months, and perioperative mortality at 30 days.
An independent committee adjudicated clinical events, and core laboratories with assessors blinded to trial group assignment adjudicated imaging results and wound assessments.
Superior efficacy, noninferior safety
Participants were about two-thirds men, largely White, with about 15% of participants being Black/African American, and more than 90% of patients in each arm had hypertension. Lesion lengths were approximately 44 mm in each group with reference vessel diameters averaging 2.82-2.94 mm before intervention. Less than 4% in each group had severe lesion calcification.
Clinical follow-up rate at 1 year in the Esprit BTK arm was 90.2% and in the angioplasty arm 90.9%. Six patients in the former arm died versus five in the latter.
At the meeting, sponsored by the Cardiovascular Research Foundation, Dr. Varcoe showed a graph of the primary efficacy results at 453 days, the extra time being allowed to achieve a diagnostic ultrasound. (P < .0001).
“As you can see, those bars start to diverge in about 5 months and continue to separate over time, showing clear superiority of the scaffold over angioplasty, absolute risk difference of 30.8% and a highly statistically significant P value,” he said. Very similar primary efficacy outcomes were seen at 393 days.
At 1 year, the secondary efficacy endpoint of binary restenosis of the target lesion occurred in 24.2% of scaffold patients versus 46.5% of the angioplasty group (P < .0001). Another secondary endpoint, freedom from above-ankle amputation, 100% total occlusion of the target vessel, or clinically driven target lesion revascularization, occurred in 82.5% of the scaffold group versus 70.4% in the angioplasty group (P = .0081).
The primary safety endpoint of freedom from a major adverse limb event plus perioperative death was 100% for angioplasty and 96.9% for Esprit BTK (P = .0019)
All subgroup analyses assessing interaction by sex, race, geographic region, or age showed Esprit BTK was superior to angioplasty, with relative risks ranging from 0.27 to 0.61.
“If this technology is approved by the FDA, it will provide a new option for our patients with very difficult-to-treat disease, which will provide them additional durability and fewer reinterventions,” Dr. Varcoe concluded. “And I think we all know deep down that’s going to translate to improved clinical outcomes and few amputations.”
David Kandzari, MD, of Peidmont Heart Institute, Atlanta, was asked to comment on the study. He said that as with other vascular interventions, the ideal technology “would be first to provide a safe and effective antiproliferative therapy that would mitigate against restenosis and for scaffolding to prevent elastic recoil and reocclusion ... and ultimately fulfill these two promises without the requisite of a permanent implant.
“Despite their common use in femoral popliteal disease, drug-coated balloons had at best demonstrated inconsistent results below the knee, and drug-coated balloons, therefore, are not approved for such indications.”
He said that drug-eluting stents have demonstrated efficacy in this indication but that these studies have been limited to fairly discrete proximal disease.
“LIFE-BTK therefore represents one of the most rigorous trials in the space of endovascular interventions as a single line and randomized trial,” Dr. Kandzari said, “showing a primary composite endpoint of both safety and effectiveness relative to conventional angioplasty.”
Dr. Kandzari pointed to strengths of the study in that it used standardization of technique with independent adjudication of both imaging and wound healing assessments. “And the study population, too, was relevant to clinical practice, representing oftentimes underrepresented groups, including those with extensive disease burden [and] clinical severity,” he said. “Importantly, in this study, nearly one-third of the population will be women.”
Panelist Jennifer Rymer, MD, of Duke University Medical Center, Durham, N.C., commented that she treats a lot of African American patients with CTLI and applauded the researchers for including those patients. “I think that this will be a groundbreaking new change in our practice,” she said.
The trial results were published simultaneously with the presentation at TCT 2023 in the New England Journal of Medicine.
Dr. Varcoe reported receiving consulting fees/honoraria from Boston Scientific Corporation, Medtronic, Abbott, BD, Intervene, Surmodics, Philips, Nectero, Alucent, W.L. Gore, Vesteck, Bard Medical, Cook Medical, and R3 Vascular. He has equity, stock, or stock options in EBR Systems and has an executive role or ownership interest in Provisio Medical and Vesteck. Dr. Kandzari received grant support/research contract from Medtronic, Teleflex, Biotronik, and CSI; consultant fees/honoraria from and is on the speaker’s bureau of CSI and Medtronic; and has equity, stock, or options in Biostar Ventures. Dr. Rymer receives grant support/research contract from Chiesi, Abbott Vascular, Abiomed, and Pfizer. The study was funded by Abbott.
A version of this article appeared on Medscape.com.
SAN FRANCISCO – An everolimus-eluting stent with a resorbable scaffold showed superior efficacy in a randomized multicenter trial when compared with angioplasty for the treatment of patients with chronic limb threatening ischemia (CLTI) resulting from infrapopliteal artery disease.
The stent (Esprit BTK, Abbott Vascular) was also noninferior to angioplasty in terms of safety.
Presenting results of the LIFE-BTK trial at the Transcatheter Cardiovascular Therapeutics annual meeting, Ramon Varcoe, MBBS, MS, PhD, MMed, of Prince of Wales Hospital, Sydney, said that peripheral artery disease is a global epidemic, the most serious manifestation of which is CTLI.
“If not treated expeditiously, this could lead to high rates of amputation, which, as we all know, has a severe impact on patients’ quality of life and even worse impact on their life prognosis, with prognosis rates worse than most cancers.”
He said that for infrapopliteal or below-the-knee (BTK) arterial disease, treatment with angioplasty has proven superior to bypass graft surgery, but some limitations of angioplasty are elastic recoil, dissection, and restenosis, thus limiting its durability. Coronary drug-eluting stents showed promise in BTK procedures but can interfere with reintervention. Thus, LIFE-BTK compared a drug-eluting stent with resorbable scaffolding to surgery.
Esprit BTK is a drug-eluting resorbable scaffold consisting of a temporary scaffold backbone of poly(L-lactide) and a strut thickness of 99 μm. It is coated with everolimus and bioresorbable poly(D,L-lactide). Two platinum markers at each end provide radiopacity.
LIFE-BTK enrolled patients aged 18 years or older with CLTI associated with ischemic rest pain or minor tissue loss and who had infrapopliteal artery stenosis or occlusion. The trial was prospective, international multicenter, and single-blind and randomly assigned 261 patients aged 18 years or older in the ratio of 2:1 to Esprit BTK (n = 173) or to angioplasty (n = 88). Treatment of up to two target lesions was allowed with a total scaffold length less than 170 mm.
The primary efficacy endpoint was superiority of Esprit BTK over angioplasty in terms of freedom of above-ankle amputation in the index limb, binary restenosis of the target lesion, and clinically driven target lesion revascularization evaluated at 1 year.
The primary safety endpoint, evaluated at 6 months, consisted of freedom from above-ankle amputation, major reintervention at 6 months, and perioperative mortality at 30 days.
An independent committee adjudicated clinical events, and core laboratories with assessors blinded to trial group assignment adjudicated imaging results and wound assessments.
Superior efficacy, noninferior safety
Participants were about two-thirds men, largely White, with about 15% of participants being Black/African American, and more than 90% of patients in each arm had hypertension. Lesion lengths were approximately 44 mm in each group with reference vessel diameters averaging 2.82-2.94 mm before intervention. Less than 4% in each group had severe lesion calcification.
Clinical follow-up rate at 1 year in the Esprit BTK arm was 90.2% and in the angioplasty arm 90.9%. Six patients in the former arm died versus five in the latter.
At the meeting, sponsored by the Cardiovascular Research Foundation, Dr. Varcoe showed a graph of the primary efficacy results at 453 days, the extra time being allowed to achieve a diagnostic ultrasound. (P < .0001).
“As you can see, those bars start to diverge in about 5 months and continue to separate over time, showing clear superiority of the scaffold over angioplasty, absolute risk difference of 30.8% and a highly statistically significant P value,” he said. Very similar primary efficacy outcomes were seen at 393 days.
At 1 year, the secondary efficacy endpoint of binary restenosis of the target lesion occurred in 24.2% of scaffold patients versus 46.5% of the angioplasty group (P < .0001). Another secondary endpoint, freedom from above-ankle amputation, 100% total occlusion of the target vessel, or clinically driven target lesion revascularization, occurred in 82.5% of the scaffold group versus 70.4% in the angioplasty group (P = .0081).
The primary safety endpoint of freedom from a major adverse limb event plus perioperative death was 100% for angioplasty and 96.9% for Esprit BTK (P = .0019)
All subgroup analyses assessing interaction by sex, race, geographic region, or age showed Esprit BTK was superior to angioplasty, with relative risks ranging from 0.27 to 0.61.
“If this technology is approved by the FDA, it will provide a new option for our patients with very difficult-to-treat disease, which will provide them additional durability and fewer reinterventions,” Dr. Varcoe concluded. “And I think we all know deep down that’s going to translate to improved clinical outcomes and few amputations.”
David Kandzari, MD, of Peidmont Heart Institute, Atlanta, was asked to comment on the study. He said that as with other vascular interventions, the ideal technology “would be first to provide a safe and effective antiproliferative therapy that would mitigate against restenosis and for scaffolding to prevent elastic recoil and reocclusion ... and ultimately fulfill these two promises without the requisite of a permanent implant.
“Despite their common use in femoral popliteal disease, drug-coated balloons had at best demonstrated inconsistent results below the knee, and drug-coated balloons, therefore, are not approved for such indications.”
He said that drug-eluting stents have demonstrated efficacy in this indication but that these studies have been limited to fairly discrete proximal disease.
“LIFE-BTK therefore represents one of the most rigorous trials in the space of endovascular interventions as a single line and randomized trial,” Dr. Kandzari said, “showing a primary composite endpoint of both safety and effectiveness relative to conventional angioplasty.”
Dr. Kandzari pointed to strengths of the study in that it used standardization of technique with independent adjudication of both imaging and wound healing assessments. “And the study population, too, was relevant to clinical practice, representing oftentimes underrepresented groups, including those with extensive disease burden [and] clinical severity,” he said. “Importantly, in this study, nearly one-third of the population will be women.”
Panelist Jennifer Rymer, MD, of Duke University Medical Center, Durham, N.C., commented that she treats a lot of African American patients with CTLI and applauded the researchers for including those patients. “I think that this will be a groundbreaking new change in our practice,” she said.
The trial results were published simultaneously with the presentation at TCT 2023 in the New England Journal of Medicine.
Dr. Varcoe reported receiving consulting fees/honoraria from Boston Scientific Corporation, Medtronic, Abbott, BD, Intervene, Surmodics, Philips, Nectero, Alucent, W.L. Gore, Vesteck, Bard Medical, Cook Medical, and R3 Vascular. He has equity, stock, or stock options in EBR Systems and has an executive role or ownership interest in Provisio Medical and Vesteck. Dr. Kandzari received grant support/research contract from Medtronic, Teleflex, Biotronik, and CSI; consultant fees/honoraria from and is on the speaker’s bureau of CSI and Medtronic; and has equity, stock, or options in Biostar Ventures. Dr. Rymer receives grant support/research contract from Chiesi, Abbott Vascular, Abiomed, and Pfizer. The study was funded by Abbott.
A version of this article appeared on Medscape.com.
AT TCT 2023
Novel hydrogel holds promise for skin regeneration
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
AT CALDERM 2023
Teens streaming on Twitch vulnerable to predators
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
AT AAP 2023
No benefit of colchicine after stroke, TIA: CHANCE-3
The anti-inflammatory agent in the CHANCE-3 trial.
The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.
Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.
Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.
The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.
The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.
Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.
The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.
Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).
All secondary outcomes were also neutral, with no differences between the two groups.
Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.
“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.
Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention.
He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.
“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added.
Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.
He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.
The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.
A version of this article first appeared on Medscape.com.
The anti-inflammatory agent in the CHANCE-3 trial.
The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.
Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.
Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.
The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.
The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.
Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.
The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.
Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).
All secondary outcomes were also neutral, with no differences between the two groups.
Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.
“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.
Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention.
He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.
“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added.
Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.
He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.
The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.
A version of this article first appeared on Medscape.com.
The anti-inflammatory agent in the CHANCE-3 trial.
The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.
Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.
Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.
The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.
The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.
Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.
The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.
Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).
All secondary outcomes were also neutral, with no differences between the two groups.
Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.
“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.
Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention.
He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.
“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added.
Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.
He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.
The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.
A version of this article first appeared on Medscape.com.
FROM WSC 2023
Ready to start engaging on social media? A dermatologist shares tips
CARLSBAD, CALIF. – In the opinion of Swati Kannan, MD, deciding whether or not to establish a presence on social media starts with a gut-check about your intentions.
“Why use it?” Dr. Kannan, a dermatologist and Mohs surgeon at the University of California, San Diego, asked attendees at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. “Isn’t being an MD or DO enough? Not anymore. and differentiates us from other nondermatology providers.”
Her favorite part about using Instagram and other social media platforms, she said, is connecting with other dermatologists and other specialists. “I’ve learned a lot from communicating with other dermatologists on different platforms, not just for social media but for changing how I practice as well.”
Dr. Kannan offered the following tips and considerations for building and maintaining a presence on social media:
Know the demographics of your practice and your target audience. In general, individuals in their 20s have a presence on many platforms, mainly TikTok for entertainment. Those in their 30s and 40s mainly use Facebook, Instagram, and YouTube, and those in their 40s-60s primarily use Facebook and YouTube. “Men tend to use YouTube, Twitter (X), Reddit, and LinkedIn, while women prefer more photo or video content platforms like Instagram, TikTok, and Facebook,” she said. In addition, knowing your target audience will help select which social media platforms to be active on.
Think about your goal. Is it a side hustle? Is it to raise awareness of various dermatologic conditions? Is it to grow your business? “Knowing this goal will help you determine how much time you’re going to commit to it.”
Do you have the time? To be effective, being active on social media can take 10-15 hours a week, especially for beginners, “so it’s like another job,” she said.
Devise a social media strategy. “Ideally, pick one to three social media platforms that you are going to be active on,” Dr. Kannan advised. “I’m active on Instagram and YouTube, and I cross-post on TikTok and Facebook. That means when I’m making content, it’s geared toward the audience on Instagram. If it hits a few people on TikTok, that’s fine, too, but the TikTok audience is not my target.”
Stick to a posting schedule. Ideally, post three to five times per week.
Create a content strategy. This includes a variety of photos, diagrams, videos, “and you want to use relevant hashtags,” she said.
Find your niche and style. This comes with time. If you specialize in a specific dermatologic condition such as psoriasis, hair loss, or vitiligo, emphasize that in your content.
Find your voice. This also comes with time. But be a professional version of yourself.
Have a plan for how to handle complaints or bad comments. “Avoid posting content that would make you a target,” she advised. “When I get a rude comment, I delete it. If the comment is racist or sexist, I will report it.”
Learn how to review the stats on your accounts. This will provide information on which posts or videos are being well received, which can serve as the basis of creating content that’s similar going forward.
Follow certain social media strategists. This can help grow followers and learn how to find trending audio or music to accompany your content. On Instagram, for example, Dr. Kannan follows @creators and @instagramforbusiness. On YouTube, she follows the Think Media channel.
Avoid posting content that would make you a target. Limit photos about partying/alcohol consumption or anything considered unprofessional. “If you can’t say it or do it in front of a patient, then you shouldn’t post it on your professional social media page,” she said.
Protect yourself. Don’t provide individual medical advice. “All of my home pages contain the statement, ‘this page is not for medical advice,’” Dr. Kannan said. “Get photo and video consent from all patients, even if you’re posting a zoomed-in version of their face. Deidentify patients as much as possible, and watermark your before and after photos and videos so that they’re not easily used by others.”
Be consistent and patient as you engage on social media platforms. Being a good digital citizen includes networking with other creators by liking and commenting on their posts, and responding to and liking comments that people make to your posts. “Remember: it’s not just about the number of followers, but also about engagement,” she said.
Dr. Kannan reported having no relevant disclosures.
CARLSBAD, CALIF. – In the opinion of Swati Kannan, MD, deciding whether or not to establish a presence on social media starts with a gut-check about your intentions.
“Why use it?” Dr. Kannan, a dermatologist and Mohs surgeon at the University of California, San Diego, asked attendees at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. “Isn’t being an MD or DO enough? Not anymore. and differentiates us from other nondermatology providers.”
Her favorite part about using Instagram and other social media platforms, she said, is connecting with other dermatologists and other specialists. “I’ve learned a lot from communicating with other dermatologists on different platforms, not just for social media but for changing how I practice as well.”
Dr. Kannan offered the following tips and considerations for building and maintaining a presence on social media:
Know the demographics of your practice and your target audience. In general, individuals in their 20s have a presence on many platforms, mainly TikTok for entertainment. Those in their 30s and 40s mainly use Facebook, Instagram, and YouTube, and those in their 40s-60s primarily use Facebook and YouTube. “Men tend to use YouTube, Twitter (X), Reddit, and LinkedIn, while women prefer more photo or video content platforms like Instagram, TikTok, and Facebook,” she said. In addition, knowing your target audience will help select which social media platforms to be active on.
Think about your goal. Is it a side hustle? Is it to raise awareness of various dermatologic conditions? Is it to grow your business? “Knowing this goal will help you determine how much time you’re going to commit to it.”
Do you have the time? To be effective, being active on social media can take 10-15 hours a week, especially for beginners, “so it’s like another job,” she said.
Devise a social media strategy. “Ideally, pick one to three social media platforms that you are going to be active on,” Dr. Kannan advised. “I’m active on Instagram and YouTube, and I cross-post on TikTok and Facebook. That means when I’m making content, it’s geared toward the audience on Instagram. If it hits a few people on TikTok, that’s fine, too, but the TikTok audience is not my target.”
Stick to a posting schedule. Ideally, post three to five times per week.
Create a content strategy. This includes a variety of photos, diagrams, videos, “and you want to use relevant hashtags,” she said.
Find your niche and style. This comes with time. If you specialize in a specific dermatologic condition such as psoriasis, hair loss, or vitiligo, emphasize that in your content.
Find your voice. This also comes with time. But be a professional version of yourself.
Have a plan for how to handle complaints or bad comments. “Avoid posting content that would make you a target,” she advised. “When I get a rude comment, I delete it. If the comment is racist or sexist, I will report it.”
Learn how to review the stats on your accounts. This will provide information on which posts or videos are being well received, which can serve as the basis of creating content that’s similar going forward.
Follow certain social media strategists. This can help grow followers and learn how to find trending audio or music to accompany your content. On Instagram, for example, Dr. Kannan follows @creators and @instagramforbusiness. On YouTube, she follows the Think Media channel.
Avoid posting content that would make you a target. Limit photos about partying/alcohol consumption or anything considered unprofessional. “If you can’t say it or do it in front of a patient, then you shouldn’t post it on your professional social media page,” she said.
Protect yourself. Don’t provide individual medical advice. “All of my home pages contain the statement, ‘this page is not for medical advice,’” Dr. Kannan said. “Get photo and video consent from all patients, even if you’re posting a zoomed-in version of their face. Deidentify patients as much as possible, and watermark your before and after photos and videos so that they’re not easily used by others.”
Be consistent and patient as you engage on social media platforms. Being a good digital citizen includes networking with other creators by liking and commenting on their posts, and responding to and liking comments that people make to your posts. “Remember: it’s not just about the number of followers, but also about engagement,” she said.
Dr. Kannan reported having no relevant disclosures.
CARLSBAD, CALIF. – In the opinion of Swati Kannan, MD, deciding whether or not to establish a presence on social media starts with a gut-check about your intentions.
“Why use it?” Dr. Kannan, a dermatologist and Mohs surgeon at the University of California, San Diego, asked attendees at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. “Isn’t being an MD or DO enough? Not anymore. and differentiates us from other nondermatology providers.”
Her favorite part about using Instagram and other social media platforms, she said, is connecting with other dermatologists and other specialists. “I’ve learned a lot from communicating with other dermatologists on different platforms, not just for social media but for changing how I practice as well.”
Dr. Kannan offered the following tips and considerations for building and maintaining a presence on social media:
Know the demographics of your practice and your target audience. In general, individuals in their 20s have a presence on many platforms, mainly TikTok for entertainment. Those in their 30s and 40s mainly use Facebook, Instagram, and YouTube, and those in their 40s-60s primarily use Facebook and YouTube. “Men tend to use YouTube, Twitter (X), Reddit, and LinkedIn, while women prefer more photo or video content platforms like Instagram, TikTok, and Facebook,” she said. In addition, knowing your target audience will help select which social media platforms to be active on.
Think about your goal. Is it a side hustle? Is it to raise awareness of various dermatologic conditions? Is it to grow your business? “Knowing this goal will help you determine how much time you’re going to commit to it.”
Do you have the time? To be effective, being active on social media can take 10-15 hours a week, especially for beginners, “so it’s like another job,” she said.
Devise a social media strategy. “Ideally, pick one to three social media platforms that you are going to be active on,” Dr. Kannan advised. “I’m active on Instagram and YouTube, and I cross-post on TikTok and Facebook. That means when I’m making content, it’s geared toward the audience on Instagram. If it hits a few people on TikTok, that’s fine, too, but the TikTok audience is not my target.”
Stick to a posting schedule. Ideally, post three to five times per week.
Create a content strategy. This includes a variety of photos, diagrams, videos, “and you want to use relevant hashtags,” she said.
Find your niche and style. This comes with time. If you specialize in a specific dermatologic condition such as psoriasis, hair loss, or vitiligo, emphasize that in your content.
Find your voice. This also comes with time. But be a professional version of yourself.
Have a plan for how to handle complaints or bad comments. “Avoid posting content that would make you a target,” she advised. “When I get a rude comment, I delete it. If the comment is racist or sexist, I will report it.”
Learn how to review the stats on your accounts. This will provide information on which posts or videos are being well received, which can serve as the basis of creating content that’s similar going forward.
Follow certain social media strategists. This can help grow followers and learn how to find trending audio or music to accompany your content. On Instagram, for example, Dr. Kannan follows @creators and @instagramforbusiness. On YouTube, she follows the Think Media channel.
Avoid posting content that would make you a target. Limit photos about partying/alcohol consumption or anything considered unprofessional. “If you can’t say it or do it in front of a patient, then you shouldn’t post it on your professional social media page,” she said.
Protect yourself. Don’t provide individual medical advice. “All of my home pages contain the statement, ‘this page is not for medical advice,’” Dr. Kannan said. “Get photo and video consent from all patients, even if you’re posting a zoomed-in version of their face. Deidentify patients as much as possible, and watermark your before and after photos and videos so that they’re not easily used by others.”
Be consistent and patient as you engage on social media platforms. Being a good digital citizen includes networking with other creators by liking and commenting on their posts, and responding to and liking comments that people make to your posts. “Remember: it’s not just about the number of followers, but also about engagement,” she said.
Dr. Kannan reported having no relevant disclosures.
AT CALDERM 2023
Teens have easy online access to Delta-8 cannabinoid products
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
At AAP 2023
Tezepelumab effective in asthma with GERD
Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the , according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.
GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.
The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.
Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.
Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.
TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.
The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).
Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).
There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).
The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.
The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.
Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the , according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.
GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.
The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.
Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.
Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.
TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.
The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).
Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).
There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).
The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.
The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.
Among patients with asthma and comorbid gastroesophageal reflux disease (GERD), the , according to a new post-hoc analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials.
GERD occurs in about 60% of asthma patients, and the comorbidity is associated with a greater risk of asthma exacerbations. “As we start doing subgroup analyses, we are looking at different comorbidities and reflux is one that’s very common and very impactful on asthma outcomes in a negative way, so it became an area of interest,” said Njira Lugogo, MD, who presented the study during a poster session at the annual meeting of the American College of Chest Physicians (CHEST). She is a professor of internal medicine and pulmonary critical care at the University of Michigan, Ann Arbor.
The analysis confirmed other findings, with comorbid GERD associated with more exacerbations, use of maintenance steroids, and high-dose inhaled steroids. “They had more disease activity, and the effect [of tezepelumab treatment] was similar whether you had reflux or didn’t have reflux. It did seem like the people without reflux had a slightly higher reduction in exacerbations, so maybe there is a slight difference, but overall it looked like both groups were really improving,” said Dr. Lugogo.
Tezepelumab is a newer biologic, having received Food and Drug Administration approval in 2021. It targets the epithelial cytokine thymic stromal lymphopoietin (TSLP), which contributes allergic inflammatory responses by acting on various innate immune cells, including dendritic cells, mast cells, and CD34+ progenitor cells. It is upregulated in the airways of asthma patients, with higher levels linked to more severe disease. A single-nucleotide polymorphism in the gene that codes TSLP has also been found to be protective against asthma, atopic asthma, and airway hyper-responsiveness.
Dr. Lugogo noted that TSLP could be a factor in how GERD may worsen trigger or worsen asthma. It is produced in the epithelium of the upper airway in response to injury, which could include aspiration into bronchial tubes attributable to GERD, and this could lead to a downstream inflammatory and immune response. “Reducing the production of or at least blocking TSLP from an epithelium that’s being irritated by acid reflux could have potential benefits. On the reverse side, could the continued presence of reflux blunt the expected response [to tezepelumab]? If someone has very severe reflux, maybe you’ve treated their asthma with tezepelumab, and they’re still having symptoms. Could it be a masquerading issue [where] you have untreated reflux contributing to ongoing symptoms, which you’re attributing to not being related to asthma? So it’s looking at it in two different ways,” said Dr. Lugogo.
TSLP is the only biologic available to treat patients with non–type 2 inflammation, which includes about 10% of adult patients, according to Dr. Lugogo. Its mechanism also influences eosinophilic and allergic asthma. When tezepelumab first became available, Dr. Lugogo noticed that physicians tended to switch to it from another biologic rather than starting it up front, but that may be changing. “I feel like more and more people are starting it up front as a therapeutic intervention, so there seems to be more and more people embracing its use in the treatment of severe asthma,” she said.
The analysis included 294 patients with asthma and GERD and 1,040 with asthma alone. Patients in the GERD comorbidity group were older (55.0 versus 48.6 years), had a higher mean body mass index (30.8 versus 27.8), and were more likely to be female (67.3% versus 63.0%).
Maintenance oral corticosteroid use was higher in the GERD group (17.0% versus 6.9%), as was use of high inhaled corticosteroid dose (78.2% versus 67.0%), frequency of nasal polyps in the previous 2 years (21.4% versus 13.8%), and experience of more than two exacerbations in the previous year (42.2% versus 34.6%).
There was a 65% reduction (95% confidence interval, 50%-76%) in annualized asthma exacerbation rate versus placebo with tezepelumab treatment in the GERD group, compared with a 58% reduction in the asthma-only group (95% CI, 48%-66%). The drug led to a 0.10 increase in forced expiratory volume in 1 second versus placebo (95% CI, 0.00-0.19) at week 52 in the GERD group, versus 0.15 (95% CI, 0.10-0.20) in the asthma-only group. Tezepelumab also improved week 52 ACQ-6 scores in the GERD group (–0.39 versus placebo; 95% CI, –0.63 to –0.14) and the asthma-only group (–0.32 versus placebo; 95% CI, –0.45 to –0.19).
The study adds to the evidence supporting tezepelumab as a promising new therapy, according to Muhammad Adrish, MD, who attended the poster session and was asked to comment on the study. “I think that this is a very interesting analysis in the sense that gastric reflux disease is a frequent comorbid condition that we see in patients with asthma, and a lot of these patients can have poor outcomes. When you look at the results from the data, you see that regardless of how sick they were and how much medication utilization these patients have at baseline, they still had a pretty decent response to tezepelumab. That speaks to the efficacy of that drug along a wide spectrum of patients,” said Dr. Adrish, who is an associate professor of pulmonary, critical care, and sleep medicine at Baylor College of Medicine, Houston.
The PATHWAY and NAVIGATOR studies were funded by Amgen. Dr. Lugogo has advised or consulted for AstraZeneca, Amgen, Regeneron, TEVA, Avillion, Sanofi, Novartis, Genentech, GSK, and Janssen. Dr. Adrish has no relevant financial disclosures.
FROM CHEST 2023
Online nicotine toothpick vendors ignore age restrictions
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
AT AAP 2023