User login
Had my patient come in today, we may have had other options
Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.
Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.
NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.
In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.
Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
Companion tests
Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.
Other approvals
T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).
T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.
For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
Trastuzumab emtansine vs. trastuzumab deruxtecan
Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.
ILDs
In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).
Chemotherapy-like adverse effects
Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.
Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.
NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.
In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.
Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
Companion tests
Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.
Other approvals
T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).
T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.
For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
Trastuzumab emtansine vs. trastuzumab deruxtecan
Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.
ILDs
In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).
Chemotherapy-like adverse effects
Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.
Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.
NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.
In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.
Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
Companion tests
Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.
Other approvals
T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).
T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.
For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
Trastuzumab emtansine vs. trastuzumab deruxtecan
Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.
ILDs
In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).
Chemotherapy-like adverse effects
Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Deep brain stimulation effective for OCD, but barriers persist
“DBS is a viable option for treatment-resistant OCD that can be expected to produce significant clinical benefit in about two out of three cases,” study investigator Wayne Goodman, MD, chair, department of psychiatry and behavioral sciences, Baylor College of Medicine, Houston, said in a statement.
However, “challenges in access still prevent many eligible individuals from getting this life-improving therapy,” co-investigator Sameer Sheth, MD, PhD, vice chair of research, department of neurosurgery at Baylor, told this news organization.
The study was published online in the Journal of Neurology, Neurosurgery and Psychiatry.
50% reduction in symptoms
The analysis included 34 studies conducted from 2005 to 2021, including 9 randomized controlled trials (RCTs) and 25 non-RCTs, involving 352 patients with treatment-resistant OCD.
Both RCTs and non-RCTs had a predominantly low risk of bias.
The results show an average 14.3-point, or 47%, reduction (P < .01) in Yale-Brown Obsessive-Compulsive Scale scores with DBS at last follow-up, with no significant difference between RCTs and non-RCTs.
Two-thirds (66%) of patients fully responded to the DBS at last follow-up, the authors found.
DBS for treatment-resistant OCD also had a “strong” effect on comorbid depression, with 47% of patients considered “full responders” relative to their preoperative (baseline) depression status and an additional 16% considered partial responders (with a 30%-49% reduction in pre/post-treatment depressive symptoms).
“The demonstrated effects of DBS in this report are even more impressive when one considers that these patients have failed numerous behavioral and pharmacological therapies,” said study investigator Eric Storch, PhD, professor and vice chair for the department of psychiatry and behavioral sciences at Baylor.
The rate of hardware-related complications was roughly 8% and infection rate was about 4% – in line with other data.
This study “offers hope for patients with severe symptoms of OCD whose disorder did not respond to a range of conventional therapies,” Dr. Goodman said.
The bigger story
Dr. Sheth said the challenges in getting appropriate OCD patients access to DBS are multifactorial.
“Psychiatrists and general practitioners and even patients are not aware of it, and insurance company policies are often out of date and ignorant of recent data such as those in this study,” Dr. Sheth explained.
“Hopefully, improved awareness in the future will reverse these trends and lead to increased access for patients in need of this therapy,” Dr. Sheth said.
Access to DBS for OCD is clearly the “bigger story” here, Brian Kopell, MD, who was not involved in the study, told this news organization.
This meta-analysis “confirms what all of us that do this with some regularity know – that DBS for OCD can be extremely helpful in patients who are refractory to standard OCD therapies,” said Dr. Kopell, department of neurosurgery and director, Center for Neuromodulation, Mount Sinai Health System, New York.
Yet, there is a dramatic difference in getting reimbursement for DBS in a case of dystonia vs. OCD.
In the United States, DBS has humanitarian device exemption for use in both dystonia and OCD, Dr. Kopell noted.
“Yet because dystonia is a movement disorder, I can get DBS for dystonia paid for by most private insurance – no big deal,” Dr. Kopell said.
“But OCD, because it’s deemed a psychiatric disorder, is treated like the redheaded stepchild and it’s monumentally hard to get insurance to pay for it – and if you can’t pay for it, you can’t do it. Simple as that,” he added.
The study was supported by the McNair Foundation and the Dana Foundation. Dr. Storch is a consultant for Biohaven and owns stock in nView. Dr. Sheth is a consultant for Boston Scientific, NeuroPace, Abbott, and Zimmer Biomet. Dr. Kopell reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“DBS is a viable option for treatment-resistant OCD that can be expected to produce significant clinical benefit in about two out of three cases,” study investigator Wayne Goodman, MD, chair, department of psychiatry and behavioral sciences, Baylor College of Medicine, Houston, said in a statement.
However, “challenges in access still prevent many eligible individuals from getting this life-improving therapy,” co-investigator Sameer Sheth, MD, PhD, vice chair of research, department of neurosurgery at Baylor, told this news organization.
The study was published online in the Journal of Neurology, Neurosurgery and Psychiatry.
50% reduction in symptoms
The analysis included 34 studies conducted from 2005 to 2021, including 9 randomized controlled trials (RCTs) and 25 non-RCTs, involving 352 patients with treatment-resistant OCD.
Both RCTs and non-RCTs had a predominantly low risk of bias.
The results show an average 14.3-point, or 47%, reduction (P < .01) in Yale-Brown Obsessive-Compulsive Scale scores with DBS at last follow-up, with no significant difference between RCTs and non-RCTs.
Two-thirds (66%) of patients fully responded to the DBS at last follow-up, the authors found.
DBS for treatment-resistant OCD also had a “strong” effect on comorbid depression, with 47% of patients considered “full responders” relative to their preoperative (baseline) depression status and an additional 16% considered partial responders (with a 30%-49% reduction in pre/post-treatment depressive symptoms).
“The demonstrated effects of DBS in this report are even more impressive when one considers that these patients have failed numerous behavioral and pharmacological therapies,” said study investigator Eric Storch, PhD, professor and vice chair for the department of psychiatry and behavioral sciences at Baylor.
The rate of hardware-related complications was roughly 8% and infection rate was about 4% – in line with other data.
This study “offers hope for patients with severe symptoms of OCD whose disorder did not respond to a range of conventional therapies,” Dr. Goodman said.
The bigger story
Dr. Sheth said the challenges in getting appropriate OCD patients access to DBS are multifactorial.
“Psychiatrists and general practitioners and even patients are not aware of it, and insurance company policies are often out of date and ignorant of recent data such as those in this study,” Dr. Sheth explained.
“Hopefully, improved awareness in the future will reverse these trends and lead to increased access for patients in need of this therapy,” Dr. Sheth said.
Access to DBS for OCD is clearly the “bigger story” here, Brian Kopell, MD, who was not involved in the study, told this news organization.
This meta-analysis “confirms what all of us that do this with some regularity know – that DBS for OCD can be extremely helpful in patients who are refractory to standard OCD therapies,” said Dr. Kopell, department of neurosurgery and director, Center for Neuromodulation, Mount Sinai Health System, New York.
Yet, there is a dramatic difference in getting reimbursement for DBS in a case of dystonia vs. OCD.
In the United States, DBS has humanitarian device exemption for use in both dystonia and OCD, Dr. Kopell noted.
“Yet because dystonia is a movement disorder, I can get DBS for dystonia paid for by most private insurance – no big deal,” Dr. Kopell said.
“But OCD, because it’s deemed a psychiatric disorder, is treated like the redheaded stepchild and it’s monumentally hard to get insurance to pay for it – and if you can’t pay for it, you can’t do it. Simple as that,” he added.
The study was supported by the McNair Foundation and the Dana Foundation. Dr. Storch is a consultant for Biohaven and owns stock in nView. Dr. Sheth is a consultant for Boston Scientific, NeuroPace, Abbott, and Zimmer Biomet. Dr. Kopell reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“DBS is a viable option for treatment-resistant OCD that can be expected to produce significant clinical benefit in about two out of three cases,” study investigator Wayne Goodman, MD, chair, department of psychiatry and behavioral sciences, Baylor College of Medicine, Houston, said in a statement.
However, “challenges in access still prevent many eligible individuals from getting this life-improving therapy,” co-investigator Sameer Sheth, MD, PhD, vice chair of research, department of neurosurgery at Baylor, told this news organization.
The study was published online in the Journal of Neurology, Neurosurgery and Psychiatry.
50% reduction in symptoms
The analysis included 34 studies conducted from 2005 to 2021, including 9 randomized controlled trials (RCTs) and 25 non-RCTs, involving 352 patients with treatment-resistant OCD.
Both RCTs and non-RCTs had a predominantly low risk of bias.
The results show an average 14.3-point, or 47%, reduction (P < .01) in Yale-Brown Obsessive-Compulsive Scale scores with DBS at last follow-up, with no significant difference between RCTs and non-RCTs.
Two-thirds (66%) of patients fully responded to the DBS at last follow-up, the authors found.
DBS for treatment-resistant OCD also had a “strong” effect on comorbid depression, with 47% of patients considered “full responders” relative to their preoperative (baseline) depression status and an additional 16% considered partial responders (with a 30%-49% reduction in pre/post-treatment depressive symptoms).
“The demonstrated effects of DBS in this report are even more impressive when one considers that these patients have failed numerous behavioral and pharmacological therapies,” said study investigator Eric Storch, PhD, professor and vice chair for the department of psychiatry and behavioral sciences at Baylor.
The rate of hardware-related complications was roughly 8% and infection rate was about 4% – in line with other data.
This study “offers hope for patients with severe symptoms of OCD whose disorder did not respond to a range of conventional therapies,” Dr. Goodman said.
The bigger story
Dr. Sheth said the challenges in getting appropriate OCD patients access to DBS are multifactorial.
“Psychiatrists and general practitioners and even patients are not aware of it, and insurance company policies are often out of date and ignorant of recent data such as those in this study,” Dr. Sheth explained.
“Hopefully, improved awareness in the future will reverse these trends and lead to increased access for patients in need of this therapy,” Dr. Sheth said.
Access to DBS for OCD is clearly the “bigger story” here, Brian Kopell, MD, who was not involved in the study, told this news organization.
This meta-analysis “confirms what all of us that do this with some regularity know – that DBS for OCD can be extremely helpful in patients who are refractory to standard OCD therapies,” said Dr. Kopell, department of neurosurgery and director, Center for Neuromodulation, Mount Sinai Health System, New York.
Yet, there is a dramatic difference in getting reimbursement for DBS in a case of dystonia vs. OCD.
In the United States, DBS has humanitarian device exemption for use in both dystonia and OCD, Dr. Kopell noted.
“Yet because dystonia is a movement disorder, I can get DBS for dystonia paid for by most private insurance – no big deal,” Dr. Kopell said.
“But OCD, because it’s deemed a psychiatric disorder, is treated like the redheaded stepchild and it’s monumentally hard to get insurance to pay for it – and if you can’t pay for it, you can’t do it. Simple as that,” he added.
The study was supported by the McNair Foundation and the Dana Foundation. Dr. Storch is a consultant for Biohaven and owns stock in nView. Dr. Sheth is a consultant for Boston Scientific, NeuroPace, Abbott, and Zimmer Biomet. Dr. Kopell reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY
Strong link found between enterovirus and type 1 diabetes
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.
The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.
Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus.
Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.
The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.
Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”
Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”
And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.
Link stronger a month after diagnosis, in close relatives, in Europe
The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.
This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.
The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.
Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)
Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).
In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).
“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.
The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.
Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).
With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).
The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).
The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.
“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.
However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”
Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.
A version of this article first appeared on Medscape.com.
AT EASD 2022
Cutaneous Eruption in an Immunocompromised Patient
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
The Diagnosis: Secondary Syphilis
Histopathology revealed a lichenoid interface dermatitis with psoriasiform hyperplasia (Figure 1A). A single spirochete was identified using immunohistochemical staining (Figure 1B). Laboratory workup revealed positive IgG and IgM treponemal antibodies and reactive rapid plasma reagin titer of 1:2048. A VDRL test performed on a cerebrospinal fluid specimen also was reactive at 1:8. A diagnosis of secondary syphilis with neurologic involvement was made, and the patient was treated with intravenous penicillin G for 14 days. Following treatment, his rapid plasma reagin decreased 4-fold with an improvement in his ocular and cutaneous symptoms.
Mucocutaneus manifestations of secondary syphilis are multitudinous. As in our patient, the classic presentation is a generalized morbilliform and papulosquamous eruption involving the palms (Figure 2) and soles. Split papules at the oral commissures, mucosal patches, and condyloma lata are the characteristic mucosal lesions of secondary syphilis.1 Patchy nonscarring alopecia is not uncommon and can be the only manifestation of secondary syphilis.2 The histopathologic features of secondary syphilis vary depending on the location and type of the skin eruption. Psoriasiform or lichenoid changes commonly occur in the epidermis and dermoepidermal junction.3 The dermal inflammatory patterns that have been described include granulomatous, nodular, and superficial and deep perivascular inflammation. The infiltrate often is composed of lymphocytes, plasma cells, and histocytes. Reactive endothelial cells and perineural plasma cell infiltrates also are common histologic features.3,4 Spirochetes can be identified in most cases using immunohistochemical staining; however, the absence of spirochetes does not exclude syphilis.3 The sensitivity of immunohistochemical staining in secondary syphilis is reported to be 71% to 100% with a very high specificity.5 The treatment for all stages of syphilis is benzathine penicillin G, and the route of administration and duration of treatment depend on the stage of disease.6
A broad differential diagnosis must be considered when encountering skin eruptions in patients with HIV. Psoriasis usually presents as circumscribed erythematous plaques with dry and silvery scaling and a predilection for the extensor surfaces of the limbs, sacrum, scalp, and nails. Nail manifestations include distal onycholysis, irregular pitting, oil spots, salmon patches, and subungual hyperkeratosis. Alopecia occasionally may be seen within scalp lesions7; however, the constellation of alopecia with a moth-eaten appearance, subungual hyperkeratosis, papulosquamous eruption, and split papules was more suggestive of secondary syphilis in our patient. In immunocompromised patients, crusted scabies can be considered for the diagnosis of papulosquamous eruptions involving the palms and soles. It often presents with symmetric, mildly pruritic, psoriasiform dermatitis that favors acral sites, but widespread involvement can be observed.8 Areas of the scalp and face can be affected in infants, elderly patients, and immunocompromised individuals. Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in scabies.
Sarcoidosis is common in Black individuals, and similar to syphilis, it is considered a great imitator of other dermatologic diseases. Frequently, it presents as redviolaceous papules, nodules, or plaques; however, rare variants including psoriasiform, ichthyosiform, verrucous, and lichenoid skin eruptions can occur. Nail dystrophy, split papules, and alopecia also have been observed.9 Ocular involvement is common and frequently presents as uveitis.10 The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation, which also may occur in syphilitic lesions9; however, a papulosquamous eruption involving the palms and soles, positive serology, and the finding of interface lichenoid dermatitis with psoriasiform hyperplasia confirmed the diagnosis of secondary syphilis in our patient. Pityriasis rubra pilaris is a rare papulosquamous disorder that can be associated with HIV (type VI/HIVassociated follicular syndrome). It presents with generalized red-orange keratotic papules and often is associated with acne conglobata, hidradenitis suppurativa, and lichen spinulosus.11 Unlike in secondary syphilis, patchy alopecia, split papules, and ocular symptoms typically are not observed in pityriasis rubra pilaris.
This case highlights many classical findings of secondary syphilis and demonstrates that, while helpful, routine skin biopsy may not be required. Treatment should be guided by clinical presentation and serologic testing while reserving skin biopsy for equivocal cases.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. J Am Acad Dermatol. 2020;82:1-14.
- Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol. 2014;53:1434-1441.
- Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004; 31:595-599.
- Flamm A, Parikh K, Xie Q, et al. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 2015;73:1025-1030.
- Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention [published online February 8, 2020]. J Am Acad Dermatol. 2020;82:17-28.
- Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020;382:845-854.
- Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983-994.
- Karthikeyan K. Crusted scabies. Indian J Dermatol Venereol Leprol. 2009;75:340-347.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. cutaneous disease. J Am Acad Dermatol. 2012;66:699.e1-718.
- Haimovic A, Sanchez M, Judson MA, et al. Sarcoidosis: a comprehensive review and update for the dermatologist: part II. extracutaneous disease. J Am Acad Dermatol. 2012;66:719.e1-730.
- Miralles E, Núñez M, De Las Heras M, et al. Pityriasis rubra pilaris and human immunodeficiency virus infection. Br J Dermatol. 1995;133:990-993.
A 29-year-old Black man with long-standing untreated HIV presented with mildly pruritic, scaly plaques on the palms and soles of 2 weeks’ duration. His medical history was notable for primary syphilis treated approximately 1 year prior. A review of symptoms was positive for blurry vision and floaters but negative for constitutional symptoms. Physical examination revealed well-defined scaly plaques over the palms, soles, and elbows with subungual hyperkeratosis. Patches of nonscarring alopecia over the scalp and split papules at the oral commissures also were noted. There were no palpable lymph nodes or genital involvement. Eye examination showed conjunctival injection and 20 cells per field in the vitreous humor. Laboratory evaluation revealed an HIV viral load of 31,623 copies/mL and a CD4 count of 47 cells/μL (reference range, 362–1531 cells/μL). A shave biopsy of the left elbow was performed for histopathologic evaluation.
BREEZE-AD-PEDS: First data for baricitinib in childhood eczema reported
The oral Janus kinase
After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.
By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).
Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
The phase 3 BREEZE-AD-PEDS trial
BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.
Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.
Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
Good results, but only with highest dose
The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).
When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.
Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.
A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
Safety of baricitinib in children
The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.
Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”
In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).
There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.
No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
Is there a role for baricitinib?
“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.
“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.
“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”
In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.
The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.
A version of this article first appeared on Medscape.com.
The oral Janus kinase
After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.
By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).
Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
The phase 3 BREEZE-AD-PEDS trial
BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.
Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.
Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
Good results, but only with highest dose
The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).
When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.
Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.
A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
Safety of baricitinib in children
The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.
Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”
In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).
There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.
No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
Is there a role for baricitinib?
“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.
“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.
“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”
In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.
The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.
A version of this article first appeared on Medscape.com.
The oral Janus kinase
After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.
By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).
Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
The phase 3 BREEZE-AD-PEDS trial
BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.
Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.
Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
Good results, but only with highest dose
The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).
When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.
Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.
A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
Safety of baricitinib in children
The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.
Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”
In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).
There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.
No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
Is there a role for baricitinib?
“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.
“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.
“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”
In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.
The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
High-dose folic acid during pregnancy tied to cancer risk in children
new data from a Scandinavian registry of more than 3 million pregnancies suggests.
The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).
There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.
The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.
“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.
The study was published online in JAMA Neurology.
Risks and benefits
Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.
To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.
Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).
The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.
Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.
In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).
There was no association between any specific ASM and childhood cancer.
“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.
They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.
“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
Practice changing?
Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”
“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.
Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.
“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.
The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new data from a Scandinavian registry of more than 3 million pregnancies suggests.
The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).
There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.
The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.
“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.
The study was published online in JAMA Neurology.
Risks and benefits
Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.
To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.
Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).
The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.
Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.
In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).
There was no association between any specific ASM and childhood cancer.
“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.
They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.
“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
Practice changing?
Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”
“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.
Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.
“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.
The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new data from a Scandinavian registry of more than 3 million pregnancies suggests.
The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).
There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.
The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.
“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.
The study was published online in JAMA Neurology.
Risks and benefits
Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.
To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.
Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).
The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.
Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.
In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).
There was no association between any specific ASM and childhood cancer.
“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.
They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.
“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
Practice changing?
Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”
“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.
Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.
“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.
The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Antifibrotic shows mixed results in RA-ILD
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
The antifibrotic pirfenidone (Esbriet) did not change the decline in forced vital capacity percentage (FVC%) from baseline of 10% or more or the risk of death compared with placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the drug appeared to slow the rate of decline in lung function, a phase 2 study indicated.
“This is the first randomized double-blind, placebo-controlled trial focused only on patients with RA-ILD,” observed Joshua Solomon, MD, National Jewish Health, Denver, and fellow TRAIL1 Network investigators.
in patients with rheumatoid arthritis and evidence of fibrotic interstitial lung disease and the totality of the evidence suggests that pirfenidone is effective in the treatment of RA-ILD,” they suggest.
The study was published online in the Lancet Respiratory Medicine.
TRAIL1
The treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) was carried out in 34 academic centers specializing in ILD. Patients had RA and the presence of ILD on high-resolution CT scan and, where possible, lung biopsy. A total of 231 patients were randomly assigned to the pirfenidone group and the remainder to placebo. The mean age of patients was 66 (interquartile range (IQR, 61.0-74.0) in the pirfenidone group and 69.56 (IQR, 63.-74.5) among placebo controls.
Patients received pirfenidone at a dose of 2,403 mg per day, given in divided doses of three 267-mg tablets, three times a day, titrated to full dose over the course of 2 weeks. High-resolution CT scans were done at the beginning and the end of the study interval. Several disease-modifying antirheumatic drugs (DMARDS) were used for the treatment of RA but no differences were observed between treatment groups accounting for the DMARD classes.
“The primary endpoint was the incidence of the composite endpoint of a decline from baseline in [FVC%] of 10% or more or death during the 52-week treatment period,” Dr. Solomon and colleagues observed. The primary outcome was measured in the intent-to-treat (ITT) population.
Some 11% of patients in the active treatment group vs. 15% of patients in the placebo group met the composite primary endpoint, as investigators reported. For the secondary endpoint of the change in FVC over 52 weeks, patients treated with pirfenidone had a slow rate of decline in lung function compared with placebo patients as measured by estimated annual change in absolute FVC (–66 ml vs. –146 mL; P = .0082).
Moreover, in a post hoc analysis by CT pattern, the effect of the antifibrotic therapy on decline in FVC was more pronounced in those with usual interstitial pneumonia pattern on imaging compared with those with any pattern of ILD, the investigators observed. Indeed, approximately half of patients with the usual interstitial pneumonia in the pirfenidone group had a significantly smaller reduction in annual change in FVC at 52 weeks compared with over three-quarters of patients with usual interstitial pneumonia treated with placebo.
In contrast, the two groups were similar with regard to the decline in FVC% by 10% more or the frequency of progression. All-cause mortality rates were similar between the two groups. Adverse events thought to be related to treatment were more frequently reported in the pirfenidone group at 44% vs. 30% of placebo patients, the most frequent of which were nausea, fatigue, and diarrhea.
“These adverse events were generally grade 1 and were not clinically significant,” as the authors emphasized, although 24% of patients receiving pirfenidone discontinued treatment because of AEs vs. only 10% of placebo patients.
Limitations of the trial included early termination because of slow recruitment and the COVID-19 pandemic. This led to underpowering of the study.
Wrong endpoint?
In an accompanying editorial, Marco Sebastiani and Andreina Manfredi, MD, said that the choice of the primary outcome of an FVC decline from a baseline of 10% or more could have negatively influenced results because an FVC decline of 10% or more was probably too challenging to show a difference between the two groups. Indeed, the updated 2022 guidelines proposed a decline of 5% or more in FVC as a “significant threshold” for disease progression in patients with progressive pulmonary fibrosis, as the editorialists pointed out.
Nevertheless, the editorialists felt that the effect of pirfenidone on the decline in FVC seems to be significant, particularly when patients with usual interstitial pneumonia are considered. ”The magnitude of the effect of pirfenidone in patients with usual interstitial pneumonia-rheumatoid arthritis-interstitial lung disease and idiopathic pulmonary fibrosis [enrolled in a different study] was very similar,” they noted, “suggesting that a careful identification of usual interstitial pneumonia pattern at HRCT [high resolution CT] could be relevant in patients with RA-ILD. Moreover, given that pirfenidone did not modify its safety in these patients, the fact that pirfenidone can be safely used with DMARD therapy is important in clinical practice.
Dr. Solomon had no conflicts of interest to declare. Dr. Sebastiani disclosed ties with Bristol Myers Squibb, Pfizer, Boehringer-Ingelheim, Lilly, Amgen, Janssen, and Celltrion. Dr. Manfredi disclosed ties with Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim. The study was funded by Genentech.
FROM THE LANCET RESPIRATORY MEDICINE
CDC: Masking no longer required in health care settings
It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.
“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.
The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.
Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.
About 73% of the country is having “high” rates of transmission, The Hill said.
“Community transmission” is different from the “community level” metric that’s used for non–health care settings.
Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”
Just 7% of counties are considered high risk, while nearly 62 percent are low.
The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.
A version of this article first appeared on WebMD.com.
It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.
“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.
The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.
Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.
About 73% of the country is having “high” rates of transmission, The Hill said.
“Community transmission” is different from the “community level” metric that’s used for non–health care settings.
Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”
Just 7% of counties are considered high risk, while nearly 62 percent are low.
The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.
A version of this article first appeared on WebMD.com.
It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.
“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.
The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.
Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.
About 73% of the country is having “high” rates of transmission, The Hill said.
“Community transmission” is different from the “community level” metric that’s used for non–health care settings.
Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”
Just 7% of counties are considered high risk, while nearly 62 percent are low.
The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.
A version of this article first appeared on WebMD.com.
FDA approves futibatinib (Lytgobi) for certain biliary tract cancers
Futibatinib was granted priority review and breakthrough designation, the agency said in its announcement.
Futibatinib is indicated for use in adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.
The FDA noted that efficacy was evaluated in a multicenter, open-label, single-arm trial (known as TAS-120-101 [NCT02052778]), which involved 103 patients with such tumors. The presence of FGFR2 fusions or other rearrangements was determined using next-generation sequencing.
All the patients in this trial received futibatinib (20 mg orally once daily) until disease progression or unacceptable toxicity.
The overall response rate was 42% (95% confidence interval, 32%-52%), and all of the 43 patients who responded achieved partial responses.
The median duration of response was 9.7 months (95% CI, 7.6-17.1).
The most common adverse reactions that occurred in 20% or more of patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
The manufacturer noted in its announcement that futibatinib covalently binds to FGFR2 and inhibits the signaling pathway. The other approved FGFR inhibitors are reversible ATP-competitive inhibitors.
The company also provided some background information on the cancer.
As a whole, cholangiocarcinoma is an aggressive cancer of the bile ducts. It is diagnosed in approximately 8000 individuals each year in the United States, the company noted.
These cases include both intrahepatic (inside the liver) and extrahepatic (outside the liver) forms of the disease. Approximately 20% of patients diagnosed with cholangiocarcinoma have the intrahepatic form of the disease. Among these 20%, approximately 10%-16% of patients have FGFR2 gene rearrangements, including fusions, which promote tumor proliferation.
Futibatinib is “a key example of the potential of precision medicine in iCCA [intrahepatic cholangiocarcinoma] and represents another advance in the treatment of this rare and challenging disease,” said medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center, Boston, and lead investigator of the pivotal study that supported the approval.
“I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years,” she commented in the company’s press release.
A version of this article first appeared on Medscape.com.
Futibatinib was granted priority review and breakthrough designation, the agency said in its announcement.
Futibatinib is indicated for use in adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.
The FDA noted that efficacy was evaluated in a multicenter, open-label, single-arm trial (known as TAS-120-101 [NCT02052778]), which involved 103 patients with such tumors. The presence of FGFR2 fusions or other rearrangements was determined using next-generation sequencing.
All the patients in this trial received futibatinib (20 mg orally once daily) until disease progression or unacceptable toxicity.
The overall response rate was 42% (95% confidence interval, 32%-52%), and all of the 43 patients who responded achieved partial responses.
The median duration of response was 9.7 months (95% CI, 7.6-17.1).
The most common adverse reactions that occurred in 20% or more of patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
The manufacturer noted in its announcement that futibatinib covalently binds to FGFR2 and inhibits the signaling pathway. The other approved FGFR inhibitors are reversible ATP-competitive inhibitors.
The company also provided some background information on the cancer.
As a whole, cholangiocarcinoma is an aggressive cancer of the bile ducts. It is diagnosed in approximately 8000 individuals each year in the United States, the company noted.
These cases include both intrahepatic (inside the liver) and extrahepatic (outside the liver) forms of the disease. Approximately 20% of patients diagnosed with cholangiocarcinoma have the intrahepatic form of the disease. Among these 20%, approximately 10%-16% of patients have FGFR2 gene rearrangements, including fusions, which promote tumor proliferation.
Futibatinib is “a key example of the potential of precision medicine in iCCA [intrahepatic cholangiocarcinoma] and represents another advance in the treatment of this rare and challenging disease,” said medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center, Boston, and lead investigator of the pivotal study that supported the approval.
“I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years,” she commented in the company’s press release.
A version of this article first appeared on Medscape.com.
Futibatinib was granted priority review and breakthrough designation, the agency said in its announcement.
Futibatinib is indicated for use in adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.
The FDA noted that efficacy was evaluated in a multicenter, open-label, single-arm trial (known as TAS-120-101 [NCT02052778]), which involved 103 patients with such tumors. The presence of FGFR2 fusions or other rearrangements was determined using next-generation sequencing.
All the patients in this trial received futibatinib (20 mg orally once daily) until disease progression or unacceptable toxicity.
The overall response rate was 42% (95% confidence interval, 32%-52%), and all of the 43 patients who responded achieved partial responses.
The median duration of response was 9.7 months (95% CI, 7.6-17.1).
The most common adverse reactions that occurred in 20% or more of patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
The manufacturer noted in its announcement that futibatinib covalently binds to FGFR2 and inhibits the signaling pathway. The other approved FGFR inhibitors are reversible ATP-competitive inhibitors.
The company also provided some background information on the cancer.
As a whole, cholangiocarcinoma is an aggressive cancer of the bile ducts. It is diagnosed in approximately 8000 individuals each year in the United States, the company noted.
These cases include both intrahepatic (inside the liver) and extrahepatic (outside the liver) forms of the disease. Approximately 20% of patients diagnosed with cholangiocarcinoma have the intrahepatic form of the disease. Among these 20%, approximately 10%-16% of patients have FGFR2 gene rearrangements, including fusions, which promote tumor proliferation.
Futibatinib is “a key example of the potential of precision medicine in iCCA [intrahepatic cholangiocarcinoma] and represents another advance in the treatment of this rare and challenging disease,” said medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center, Boston, and lead investigator of the pivotal study that supported the approval.
“I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years,” she commented in the company’s press release.
A version of this article first appeared on Medscape.com.
Instagram: Cosmetic procedures discussed without cosmetic experts
according to an analysis of related posts on the photo-sharing service.
“Given that there is little to no oversight on social networking sites, unqualified sources can widely disseminate misinformation resulting in misguided management or unnecessary procedures,” Taryn N. Murray, MD, and associates said in Lasers in Surgery and Medicine.
They generated a list of 25 hashtags related to nonsurgical cosmetic procedures, which were queried on Instagram on Jan. 2-3, 2022. The most popular was #Botox, with 12.1 million posts, followed by #Laser with 6.7 million, and #Filler with 3.5 million. Each of the 25 hashtags had at least 250,000 posts, they reported.
“Studies have shown that cosmetic patients and younger patients value social media when selecting a provider and patients often make treatment decisions based on social media,” they noted.
The bulk of the study involved “the first 10 posts displayed under the ‘Top’ section for each hashtag, as sorted by Instagram’s proprietary algorithm,” explained Dr. Murray and associates at the Dermatology and Laser Surgery Center in Houston. The 250 posts eventually selected for inclusion each received scrutiny in terms of content type and creator credentials.
Physicians in core cosmetic specialties – dermatology, plastic surgery, facial plastic surgery, and oculoplastic surgery – created just 12% of those 250 posts, compared with 68% for nonphysician providers, 13% for consumers/others, and 8% for other physicians, they said.
Educational content made up the largest share (38%) of posts by core cosmetic physicians, with before-and-after next at 31%, self-promotional at 21%, and personal at 10%. Nonphysician providers were the most likely to create before-and-after (49% of their total) and self-promotional (28%) content, while consumers had the largest share of promotional posts (31%) and other physicians posted the most entertainment content (25%), the researchers said.
An overall look at the content shows that the largest proportion of all 250 posts included in the analysis involved before-and-after photos (45%), with self-promotion next at 23%. Education represented just 17% of the posting total for nonsurgical cosmetic procedures, with personal, entertainment, and promotional each at 5%, Dr. Murray and associates reported.
By recognizing “the role social media plays in patients’ understanding of and desire to undergo nonsurgical cosmetic procedures” and “increasing their presence on Instagram, core cosmetic physicians can provide patient education, counteract misinformation, and raise awareness on training and qualifications,” they wrote.
The study authors did not provide any disclosures regarding funding or financial conflicts.
according to an analysis of related posts on the photo-sharing service.
“Given that there is little to no oversight on social networking sites, unqualified sources can widely disseminate misinformation resulting in misguided management or unnecessary procedures,” Taryn N. Murray, MD, and associates said in Lasers in Surgery and Medicine.
They generated a list of 25 hashtags related to nonsurgical cosmetic procedures, which were queried on Instagram on Jan. 2-3, 2022. The most popular was #Botox, with 12.1 million posts, followed by #Laser with 6.7 million, and #Filler with 3.5 million. Each of the 25 hashtags had at least 250,000 posts, they reported.
“Studies have shown that cosmetic patients and younger patients value social media when selecting a provider and patients often make treatment decisions based on social media,” they noted.
The bulk of the study involved “the first 10 posts displayed under the ‘Top’ section for each hashtag, as sorted by Instagram’s proprietary algorithm,” explained Dr. Murray and associates at the Dermatology and Laser Surgery Center in Houston. The 250 posts eventually selected for inclusion each received scrutiny in terms of content type and creator credentials.
Physicians in core cosmetic specialties – dermatology, plastic surgery, facial plastic surgery, and oculoplastic surgery – created just 12% of those 250 posts, compared with 68% for nonphysician providers, 13% for consumers/others, and 8% for other physicians, they said.
Educational content made up the largest share (38%) of posts by core cosmetic physicians, with before-and-after next at 31%, self-promotional at 21%, and personal at 10%. Nonphysician providers were the most likely to create before-and-after (49% of their total) and self-promotional (28%) content, while consumers had the largest share of promotional posts (31%) and other physicians posted the most entertainment content (25%), the researchers said.
An overall look at the content shows that the largest proportion of all 250 posts included in the analysis involved before-and-after photos (45%), with self-promotion next at 23%. Education represented just 17% of the posting total for nonsurgical cosmetic procedures, with personal, entertainment, and promotional each at 5%, Dr. Murray and associates reported.
By recognizing “the role social media plays in patients’ understanding of and desire to undergo nonsurgical cosmetic procedures” and “increasing their presence on Instagram, core cosmetic physicians can provide patient education, counteract misinformation, and raise awareness on training and qualifications,” they wrote.
The study authors did not provide any disclosures regarding funding or financial conflicts.
according to an analysis of related posts on the photo-sharing service.
“Given that there is little to no oversight on social networking sites, unqualified sources can widely disseminate misinformation resulting in misguided management or unnecessary procedures,” Taryn N. Murray, MD, and associates said in Lasers in Surgery and Medicine.
They generated a list of 25 hashtags related to nonsurgical cosmetic procedures, which were queried on Instagram on Jan. 2-3, 2022. The most popular was #Botox, with 12.1 million posts, followed by #Laser with 6.7 million, and #Filler with 3.5 million. Each of the 25 hashtags had at least 250,000 posts, they reported.
“Studies have shown that cosmetic patients and younger patients value social media when selecting a provider and patients often make treatment decisions based on social media,” they noted.
The bulk of the study involved “the first 10 posts displayed under the ‘Top’ section for each hashtag, as sorted by Instagram’s proprietary algorithm,” explained Dr. Murray and associates at the Dermatology and Laser Surgery Center in Houston. The 250 posts eventually selected for inclusion each received scrutiny in terms of content type and creator credentials.
Physicians in core cosmetic specialties – dermatology, plastic surgery, facial plastic surgery, and oculoplastic surgery – created just 12% of those 250 posts, compared with 68% for nonphysician providers, 13% for consumers/others, and 8% for other physicians, they said.
Educational content made up the largest share (38%) of posts by core cosmetic physicians, with before-and-after next at 31%, self-promotional at 21%, and personal at 10%. Nonphysician providers were the most likely to create before-and-after (49% of their total) and self-promotional (28%) content, while consumers had the largest share of promotional posts (31%) and other physicians posted the most entertainment content (25%), the researchers said.
An overall look at the content shows that the largest proportion of all 250 posts included in the analysis involved before-and-after photos (45%), with self-promotion next at 23%. Education represented just 17% of the posting total for nonsurgical cosmetic procedures, with personal, entertainment, and promotional each at 5%, Dr. Murray and associates reported.
By recognizing “the role social media plays in patients’ understanding of and desire to undergo nonsurgical cosmetic procedures” and “increasing their presence on Instagram, core cosmetic physicians can provide patient education, counteract misinformation, and raise awareness on training and qualifications,” they wrote.
The study authors did not provide any disclosures regarding funding or financial conflicts.
FROM LASERS IN SURGERY AND MEDICINE