News

TOPLINE:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An analysis of acne-specific patient-reported outcome measures (PROMs) identified LGBTQ+-noninclusive language in four of nine measures, with heteronormative terms used in three of six measures addressing intimate relationships. 

METHODOLOGY:

• Researchers conducted an inductive thematic analysis of 22 PROMs for acne, identified through a PubMed search.
• LGBTQ+-inclusive language was defined per the National Institutes of Health style guide.
• The analysis included 16 PROMs: Nine were acne-specific with 56 relevant items, 4 were dermatology-specific with 28 items, and 4 were health-related with 43 items.

TAKEAWAY:

• LGBTQ+-noninclusive language was identified in four of nine acne-specific PROMs — the Acne Disability Index (ADI), Acne Quality of Life Scale (AQOL), Acne-Quality of Life (Acne-QoL), and Cardiff Acne Disability Index (CADI) — but not in health-related or dermatology-specific PROMs.
• Among PROMs addressing intimate relationships, three of six acne-specific measures (CADI, ADI, and Acne-QoL) used heteronormative language, while three acne-specific PROMs, three dermatology-specific PROMs, and one health-related PROM used nonheteronormative terminology (such as “partner”).
• All PROMs contained items with nongendered pronouns (such as “I” or “you” instead of “he” or “she”). However, the AQOL included gendered language (“brothers” and “sisters,” rather than “siblings”).
• Two acne-specific PROMs demonstrated partial LGBTQ+ inclusivity, incorporating some but not all LGBTQ+ identities.

IN PRACTICE:

“Using LGBTQ+-inclusive language may promote the acquisition of accurate and relevant data for patient care and clinical trials and even enhance patient-clinician relationships,” the authors of the study wrote. “While demographics such as sex, age, race, and ethnicity are commonly considered during patient-reported outcome development and validation,” wrote the authors of an accompanying editorial, the study highlights that “sexual orientation and gender identity should also be considered to ensure these measures have similar performance across diverse populations.” 

SOURCE:

The study was led by Twan Sia, BA, Department of Dermatology, Stanford University School of Medicine in California. The authors of the editorial were John S. Barbieri, MD, MBA, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Mya L. Roberson, MSPH, PhD, University of North Carolina at Chapel Hill.

LIMITATIONS:

The study was limited to the analysis of only English-language PROMs. 

DISCLOSURES:

Two study authors disclosed receiving grants or personal fees from various sources, including pharmaceutical companies outside the submitted work. Barbieri disclosed receiving consulting fees from Dexcel Pharma and Honeydew Care; Roberson disclosed receiving consulting fees from the National Committee for Quality Assurance.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An analysis of acne-specific patient-reported outcome measures (PROMs) identified LGBTQ+-noninclusive language in four of nine measures, with heteronormative terms used in three of six measures addressing intimate relationships. 

METHODOLOGY:

• Researchers conducted an inductive thematic analysis of 22 PROMs for acne, identified through a PubMed search.
• LGBTQ+-inclusive language was defined per the National Institutes of Health style guide.
• The analysis included 16 PROMs: Nine were acne-specific with 56 relevant items, 4 were dermatology-specific with 28 items, and 4 were health-related with 43 items.

TAKEAWAY:

• LGBTQ+-noninclusive language was identified in four of nine acne-specific PROMs — the Acne Disability Index (ADI), Acne Quality of Life Scale (AQOL), Acne-Quality of Life (Acne-QoL), and Cardiff Acne Disability Index (CADI) — but not in health-related or dermatology-specific PROMs.
• Among PROMs addressing intimate relationships, three of six acne-specific measures (CADI, ADI, and Acne-QoL) used heteronormative language, while three acne-specific PROMs, three dermatology-specific PROMs, and one health-related PROM used nonheteronormative terminology (such as “partner”).
• All PROMs contained items with nongendered pronouns (such as “I” or “you” instead of “he” or “she”). However, the AQOL included gendered language (“brothers” and “sisters,” rather than “siblings”).
• Two acne-specific PROMs demonstrated partial LGBTQ+ inclusivity, incorporating some but not all LGBTQ+ identities.

IN PRACTICE:

“Using LGBTQ+-inclusive language may promote the acquisition of accurate and relevant data for patient care and clinical trials and even enhance patient-clinician relationships,” the authors of the study wrote. “While demographics such as sex, age, race, and ethnicity are commonly considered during patient-reported outcome development and validation,” wrote the authors of an accompanying editorial, the study highlights that “sexual orientation and gender identity should also be considered to ensure these measures have similar performance across diverse populations.” 

SOURCE:

The study was led by Twan Sia, BA, Department of Dermatology, Stanford University School of Medicine in California. The authors of the editorial were John S. Barbieri, MD, MBA, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Mya L. Roberson, MSPH, PhD, University of North Carolina at Chapel Hill.

LIMITATIONS:

The study was limited to the analysis of only English-language PROMs. 

DISCLOSURES:

Two study authors disclosed receiving grants or personal fees from various sources, including pharmaceutical companies outside the submitted work. Barbieri disclosed receiving consulting fees from Dexcel Pharma and Honeydew Care; Roberson disclosed receiving consulting fees from the National Committee for Quality Assurance.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An analysis of acne-specific patient-reported outcome measures (PROMs) identified LGBTQ+-noninclusive language in four of nine measures, with heteronormative terms used in three of six measures addressing intimate relationships. 

METHODOLOGY:

• Researchers conducted an inductive thematic analysis of 22 PROMs for acne, identified through a PubMed search.
• LGBTQ+-inclusive language was defined per the National Institutes of Health style guide.
• The analysis included 16 PROMs: Nine were acne-specific with 56 relevant items, 4 were dermatology-specific with 28 items, and 4 were health-related with 43 items.

TAKEAWAY:

• LGBTQ+-noninclusive language was identified in four of nine acne-specific PROMs — the Acne Disability Index (ADI), Acne Quality of Life Scale (AQOL), Acne-Quality of Life (Acne-QoL), and Cardiff Acne Disability Index (CADI) — but not in health-related or dermatology-specific PROMs.
• Among PROMs addressing intimate relationships, three of six acne-specific measures (CADI, ADI, and Acne-QoL) used heteronormative language, while three acne-specific PROMs, three dermatology-specific PROMs, and one health-related PROM used nonheteronormative terminology (such as “partner”).
• All PROMs contained items with nongendered pronouns (such as “I” or “you” instead of “he” or “she”). However, the AQOL included gendered language (“brothers” and “sisters,” rather than “siblings”).
• Two acne-specific PROMs demonstrated partial LGBTQ+ inclusivity, incorporating some but not all LGBTQ+ identities.

IN PRACTICE:

“Using LGBTQ+-inclusive language may promote the acquisition of accurate and relevant data for patient care and clinical trials and even enhance patient-clinician relationships,” the authors of the study wrote. “While demographics such as sex, age, race, and ethnicity are commonly considered during patient-reported outcome development and validation,” wrote the authors of an accompanying editorial, the study highlights that “sexual orientation and gender identity should also be considered to ensure these measures have similar performance across diverse populations.” 

SOURCE:

The study was led by Twan Sia, BA, Department of Dermatology, Stanford University School of Medicine in California. The authors of the editorial were John S. Barbieri, MD, MBA, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, and Mya L. Roberson, MSPH, PhD, University of North Carolina at Chapel Hill.

LIMITATIONS:

The study was limited to the analysis of only English-language PROMs. 

DISCLOSURES:

Two study authors disclosed receiving grants or personal fees from various sources, including pharmaceutical companies outside the submitted work. Barbieri disclosed receiving consulting fees from Dexcel Pharma and Honeydew Care; Roberson disclosed receiving consulting fees from the National Committee for Quality Assurance.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

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

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

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

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

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

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

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

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

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

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

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

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine. 

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine. 

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.