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Birch bark–derived treatment reduces daily dressings in patients with epidermolysis bullosa
Additional when compared with a control gel.
In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.
Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.
The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).
“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.
“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).
“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.
Approved in Europe, not in the United States
Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.
Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.
EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.
The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.
Dr. Kiritsi summarized the main results of the EASE trial as follows.
- Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
- Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
- Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
- Improved pain among participants aged 4 years and older while their dressings were being changed.
- Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
- Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.
The EASE study – an important trial for EB
EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.
“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.
“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.
The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.
A version of this article appeared on Medscape.com.
Additional when compared with a control gel.
In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.
Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.
The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).
“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.
“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).
“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.
Approved in Europe, not in the United States
Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.
Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.
EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.
The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.
Dr. Kiritsi summarized the main results of the EASE trial as follows.
- Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
- Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
- Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
- Improved pain among participants aged 4 years and older while their dressings were being changed.
- Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
- Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.
The EASE study – an important trial for EB
EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.
“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.
“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.
The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.
A version of this article appeared on Medscape.com.
Additional when compared with a control gel.
In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.
Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.
The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).
“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.
“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).
“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.
Approved in Europe, not in the United States
Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.
Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.
EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.
The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.
Dr. Kiritsi summarized the main results of the EASE trial as follows.
- Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
- Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
- Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
- Improved pain among participants aged 4 years and older while their dressings were being changed.
- Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
- Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.
The EASE study – an important trial for EB
EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.
“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.
“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.
The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.
A version of this article appeared on Medscape.com.
FROM THE EADV CONGRESS
Perinatal depression rarely stands alone
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Survey finds oral minoxidil shortage in Washington-area pharmacies
A .
Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.
Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.
“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.
Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.
Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.
After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.
Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.
For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.
Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.
Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.
Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers. ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.
Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.
But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.
The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.
Dr. Friedman reports no relevant financial relationships.
This story was updated on 11/2/2023.
A .
Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.
Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.
“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.
Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.
Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.
After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.
Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.
For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.
Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.
Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.
Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers. ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.
Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.
But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.
The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.
Dr. Friedman reports no relevant financial relationships.
This story was updated on 11/2/2023.
A .
Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.
Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.
“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.
Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.
Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.
After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.
Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.
For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.
Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.
Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.
Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers. ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.
Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.
But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.
The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.
Dr. Friedman reports no relevant financial relationships.
This story was updated on 11/2/2023.
FROM THE JOURNAL OF DRUGS IN DERMATOLOGY
More on disruption of the default mode network
In a recent editorial, “Is the contemporary mental health crisis among youth due to DMN disruption?” (
First, Dr. Nasrallah referred to the well-cited review by Whitfield-Gabrieli et al1 regarding the relationship between DMN activation and mental health problems. However, this review shows that in mental health problems like “schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected.” This stands in contradiction with the theory of decreased DMN activity in youth with mental health problems, and would, according to Dr. Nasrallah’s theory, call for more, not less, social media use.
Second, Dr. Nasrallah’s theory implies a substantial relationship between social media use and mental health problems. The latest umbrella review on the topic included 25 reviews, of which the majority found either “inconsistent” results or only “weak evidence” for a relationship.2 Additionally, a study of 355,358 adolescents found that digital technology use explains only 0.4% of the variance of well-being.3
Third, there are many focused attention tasks other than video games and social media, such as reading, doing math homework, and playing chess. Dr. Nasrallah’s theory suggests that the World Health Organization should refrain from global efforts to get more kids into schools, given that this would increase the amount of focused attention tasks, reduce DMN activation, and increase the amount of mental health problems.
Fourth, youth mental health problems are multifactorial. Identified predictors include “female gender, low socioeconomic status, higher stress reactivity, conduct issues, substance misuse, and problems in peer and parental relationships.”4 Given that these factors are unrelated to the DMN, under-activation of the DMN cannot “explain” the youth mental health crisis, as the editorial suggested.
1. Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol. 2012;8:49-76. doi:10.1146/annurev-clinpsy-032511-143049
2. Valkenburg PM, Meier A, Beyens I. Social media use and its impact on adolescent mental health: an umbrella review of the evidence. Curr Opin Psychol. 2022;44:58-68. doi:10.1016/j.copsyc.2021.08.017
3. Orben A, Przybylski AK. The association between adolescent well-being and digital technology use. Nat Hum Behav. 2019;3(2):173-182. doi:10.1038/s41562-018-0506-1
4. Shore L, Toumbourou JW, Lewis AJ, et al. Review: longitudinal trajectories of child and adolescent depressive symptoms and their predictors - a systematic review and meta-analysis. Child Adolesc Ment Health. 2018;23(2):107-120. doi:10.1111/camh.12220
In a recent editorial, “Is the contemporary mental health crisis among youth due to DMN disruption?” (
First, Dr. Nasrallah referred to the well-cited review by Whitfield-Gabrieli et al1 regarding the relationship between DMN activation and mental health problems. However, this review shows that in mental health problems like “schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected.” This stands in contradiction with the theory of decreased DMN activity in youth with mental health problems, and would, according to Dr. Nasrallah’s theory, call for more, not less, social media use.
Second, Dr. Nasrallah’s theory implies a substantial relationship between social media use and mental health problems. The latest umbrella review on the topic included 25 reviews, of which the majority found either “inconsistent” results or only “weak evidence” for a relationship.2 Additionally, a study of 355,358 adolescents found that digital technology use explains only 0.4% of the variance of well-being.3
Third, there are many focused attention tasks other than video games and social media, such as reading, doing math homework, and playing chess. Dr. Nasrallah’s theory suggests that the World Health Organization should refrain from global efforts to get more kids into schools, given that this would increase the amount of focused attention tasks, reduce DMN activation, and increase the amount of mental health problems.
Fourth, youth mental health problems are multifactorial. Identified predictors include “female gender, low socioeconomic status, higher stress reactivity, conduct issues, substance misuse, and problems in peer and parental relationships.”4 Given that these factors are unrelated to the DMN, under-activation of the DMN cannot “explain” the youth mental health crisis, as the editorial suggested.
In a recent editorial, “Is the contemporary mental health crisis among youth due to DMN disruption?” (
First, Dr. Nasrallah referred to the well-cited review by Whitfield-Gabrieli et al1 regarding the relationship between DMN activation and mental health problems. However, this review shows that in mental health problems like “schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected.” This stands in contradiction with the theory of decreased DMN activity in youth with mental health problems, and would, according to Dr. Nasrallah’s theory, call for more, not less, social media use.
Second, Dr. Nasrallah’s theory implies a substantial relationship between social media use and mental health problems. The latest umbrella review on the topic included 25 reviews, of which the majority found either “inconsistent” results or only “weak evidence” for a relationship.2 Additionally, a study of 355,358 adolescents found that digital technology use explains only 0.4% of the variance of well-being.3
Third, there are many focused attention tasks other than video games and social media, such as reading, doing math homework, and playing chess. Dr. Nasrallah’s theory suggests that the World Health Organization should refrain from global efforts to get more kids into schools, given that this would increase the amount of focused attention tasks, reduce DMN activation, and increase the amount of mental health problems.
Fourth, youth mental health problems are multifactorial. Identified predictors include “female gender, low socioeconomic status, higher stress reactivity, conduct issues, substance misuse, and problems in peer and parental relationships.”4 Given that these factors are unrelated to the DMN, under-activation of the DMN cannot “explain” the youth mental health crisis, as the editorial suggested.
1. Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol. 2012;8:49-76. doi:10.1146/annurev-clinpsy-032511-143049
2. Valkenburg PM, Meier A, Beyens I. Social media use and its impact on adolescent mental health: an umbrella review of the evidence. Curr Opin Psychol. 2022;44:58-68. doi:10.1016/j.copsyc.2021.08.017
3. Orben A, Przybylski AK. The association between adolescent well-being and digital technology use. Nat Hum Behav. 2019;3(2):173-182. doi:10.1038/s41562-018-0506-1
4. Shore L, Toumbourou JW, Lewis AJ, et al. Review: longitudinal trajectories of child and adolescent depressive symptoms and their predictors - a systematic review and meta-analysis. Child Adolesc Ment Health. 2018;23(2):107-120. doi:10.1111/camh.12220
1. Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol. 2012;8:49-76. doi:10.1146/annurev-clinpsy-032511-143049
2. Valkenburg PM, Meier A, Beyens I. Social media use and its impact on adolescent mental health: an umbrella review of the evidence. Curr Opin Psychol. 2022;44:58-68. doi:10.1016/j.copsyc.2021.08.017
3. Orben A, Przybylski AK. The association between adolescent well-being and digital technology use. Nat Hum Behav. 2019;3(2):173-182. doi:10.1038/s41562-018-0506-1
4. Shore L, Toumbourou JW, Lewis AJ, et al. Review: longitudinal trajectories of child and adolescent depressive symptoms and their predictors - a systematic review and meta-analysis. Child Adolesc Ment Health. 2018;23(2):107-120. doi:10.1111/camh.12220
Commentary: Recent Practice-Changing Studies in LBCL and MCL, November 2023
The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.3 Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.
Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.4 Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.
Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.5 This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.
Additional References
1. Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
2. Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6
3. Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162
4. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520
5. Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712
The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.3 Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.
Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.4 Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.
Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.5 This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.
Additional References
1. Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
2. Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6
3. Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162
4. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520
5. Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712
The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.3 Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.
Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.4 Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.
Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.5 This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.
Additional References
1. Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
2. Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6
3. Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162
4. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520
5. Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712
Commentary: RA Treatment Strategies, November 2023
Given the frequency of autoimmune conditions in women, the possible effects of estrogen and hormonal therapy exposure over the lifespan on the development of rheumatoid arthritis (RA) has long been of interest. Prior studies have identified a potential increase in RA risk in older women taking estrogen replacement. Hadizadeh and colleagues used the UK Biobank to identify cases of RA among over 236,000 women taking oral contraceptives and over 102,000 women taking hormone replacement therapy. Oral contraceptive use was associated with lower risk for RA (hazard ratio [HR] 0.89), whereas hormone replacement therapy was associated with higher risk for RA (HR 1.16) compared with women who had never used these therapies. Exogenous estrogen exposure may affect the development of RA, but the potential mechanisms (including the effect on systemic inflammation) remain unclear.
Among the multitude of studies on a treat-to-target (T2T) strategy in RA, a recent cluster randomized trial by Bessette and colleagues compared use of abatacept in 284 patients treated by 44 physicians. Patients assigned to both T2T and routine care had significant improvement in RA disease activity (as measured by the Clinical Disease Activity Index) with abatacept, with close to 40% in low disease activity at 12 months. Those treated with routine care experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with slightly higher odds of low disease activity and a shorter time to Simplified Disease Activity Index remission (14 vs 19 months). With T2T being largely accepted as a standard of care on the basis of prior studies, this study raises the question of why little difference was seen between the two groups — perhaps it was related to the use of abatacept. It is unlikely to further change the standard of care to reduce use of disease activity measures.
To better understand refractory or difficult-to-treat (D2T) RA, Jung and colleagues used the KOBIO (KOrean College of Rheumatology BIOlogics) registry to compare characteristics of patients with D2T RA vs those who respond more readily to therapy. Of the 2321 patients included in the study, about 12% (271) had D2T RA. Patients with D2T RA tended to be younger and have longer disease duration, as well as a negative rheumatoid factor (RF); less use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD); and, as expected, higher disease activity measures. Given that about 80% of patients were seropositive for RF and the fact that patients with D2T RA tended to have higher inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), it is not likely that patients were misclassified with RA. The reason why patients with D2T RA had less csDMARD use is not clear, but prior studies have supported early and aggressive use of csDMARD for best outcomes. The study did suggest that patients with D2T RA stayed on Janus kinase (JAK) inhibitor therapy the longest, and perhaps similar studies in future will help outline the best treatment strategy for patients with D2T RA and persistently high disease activity.
Finally, in a post hoc analysis of the ORAL Start trial of the JAK inhibitor tofacitinib vs methotrexate, Ciurea and colleagues looked at paired joint pathology scores (PJPS) — swollen and tender joint counts with left and right pooled — over the course of the 12-month study. Patients receiving tofacitinib had overall improved PJPS, though patients receiving methotrexate had more improvement in the foot. These findings, generally supporting those of the initial study, are unlikely to further change therapy.
Given the frequency of autoimmune conditions in women, the possible effects of estrogen and hormonal therapy exposure over the lifespan on the development of rheumatoid arthritis (RA) has long been of interest. Prior studies have identified a potential increase in RA risk in older women taking estrogen replacement. Hadizadeh and colleagues used the UK Biobank to identify cases of RA among over 236,000 women taking oral contraceptives and over 102,000 women taking hormone replacement therapy. Oral contraceptive use was associated with lower risk for RA (hazard ratio [HR] 0.89), whereas hormone replacement therapy was associated with higher risk for RA (HR 1.16) compared with women who had never used these therapies. Exogenous estrogen exposure may affect the development of RA, but the potential mechanisms (including the effect on systemic inflammation) remain unclear.
Among the multitude of studies on a treat-to-target (T2T) strategy in RA, a recent cluster randomized trial by Bessette and colleagues compared use of abatacept in 284 patients treated by 44 physicians. Patients assigned to both T2T and routine care had significant improvement in RA disease activity (as measured by the Clinical Disease Activity Index) with abatacept, with close to 40% in low disease activity at 12 months. Those treated with routine care experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with slightly higher odds of low disease activity and a shorter time to Simplified Disease Activity Index remission (14 vs 19 months). With T2T being largely accepted as a standard of care on the basis of prior studies, this study raises the question of why little difference was seen between the two groups — perhaps it was related to the use of abatacept. It is unlikely to further change the standard of care to reduce use of disease activity measures.
To better understand refractory or difficult-to-treat (D2T) RA, Jung and colleagues used the KOBIO (KOrean College of Rheumatology BIOlogics) registry to compare characteristics of patients with D2T RA vs those who respond more readily to therapy. Of the 2321 patients included in the study, about 12% (271) had D2T RA. Patients with D2T RA tended to be younger and have longer disease duration, as well as a negative rheumatoid factor (RF); less use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD); and, as expected, higher disease activity measures. Given that about 80% of patients were seropositive for RF and the fact that patients with D2T RA tended to have higher inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), it is not likely that patients were misclassified with RA. The reason why patients with D2T RA had less csDMARD use is not clear, but prior studies have supported early and aggressive use of csDMARD for best outcomes. The study did suggest that patients with D2T RA stayed on Janus kinase (JAK) inhibitor therapy the longest, and perhaps similar studies in future will help outline the best treatment strategy for patients with D2T RA and persistently high disease activity.
Finally, in a post hoc analysis of the ORAL Start trial of the JAK inhibitor tofacitinib vs methotrexate, Ciurea and colleagues looked at paired joint pathology scores (PJPS) — swollen and tender joint counts with left and right pooled — over the course of the 12-month study. Patients receiving tofacitinib had overall improved PJPS, though patients receiving methotrexate had more improvement in the foot. These findings, generally supporting those of the initial study, are unlikely to further change therapy.
Given the frequency of autoimmune conditions in women, the possible effects of estrogen and hormonal therapy exposure over the lifespan on the development of rheumatoid arthritis (RA) has long been of interest. Prior studies have identified a potential increase in RA risk in older women taking estrogen replacement. Hadizadeh and colleagues used the UK Biobank to identify cases of RA among over 236,000 women taking oral contraceptives and over 102,000 women taking hormone replacement therapy. Oral contraceptive use was associated with lower risk for RA (hazard ratio [HR] 0.89), whereas hormone replacement therapy was associated with higher risk for RA (HR 1.16) compared with women who had never used these therapies. Exogenous estrogen exposure may affect the development of RA, but the potential mechanisms (including the effect on systemic inflammation) remain unclear.
Among the multitude of studies on a treat-to-target (T2T) strategy in RA, a recent cluster randomized trial by Bessette and colleagues compared use of abatacept in 284 patients treated by 44 physicians. Patients assigned to both T2T and routine care had significant improvement in RA disease activity (as measured by the Clinical Disease Activity Index) with abatacept, with close to 40% in low disease activity at 12 months. Those treated with routine care experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with slightly higher odds of low disease activity and a shorter time to Simplified Disease Activity Index remission (14 vs 19 months). With T2T being largely accepted as a standard of care on the basis of prior studies, this study raises the question of why little difference was seen between the two groups — perhaps it was related to the use of abatacept. It is unlikely to further change the standard of care to reduce use of disease activity measures.
To better understand refractory or difficult-to-treat (D2T) RA, Jung and colleagues used the KOBIO (KOrean College of Rheumatology BIOlogics) registry to compare characteristics of patients with D2T RA vs those who respond more readily to therapy. Of the 2321 patients included in the study, about 12% (271) had D2T RA. Patients with D2T RA tended to be younger and have longer disease duration, as well as a negative rheumatoid factor (RF); less use of conventional synthetic disease-modifying antirheumatic drugs (csDMARD); and, as expected, higher disease activity measures. Given that about 80% of patients were seropositive for RF and the fact that patients with D2T RA tended to have higher inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), it is not likely that patients were misclassified with RA. The reason why patients with D2T RA had less csDMARD use is not clear, but prior studies have supported early and aggressive use of csDMARD for best outcomes. The study did suggest that patients with D2T RA stayed on Janus kinase (JAK) inhibitor therapy the longest, and perhaps similar studies in future will help outline the best treatment strategy for patients with D2T RA and persistently high disease activity.
Finally, in a post hoc analysis of the ORAL Start trial of the JAK inhibitor tofacitinib vs methotrexate, Ciurea and colleagues looked at paired joint pathology scores (PJPS) — swollen and tender joint counts with left and right pooled — over the course of the 12-month study. Patients receiving tofacitinib had overall improved PJPS, though patients receiving methotrexate had more improvement in the foot. These findings, generally supporting those of the initial study, are unlikely to further change therapy.
AI flagged skin cancer with near-perfect accuracy, in UK study
. AI detected more than 99% of all skin cancers.
The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.
Skin cancer is the most common cancer in the United States; one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.
Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.
The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.
“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.
Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.
The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.
Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.
Limitations
The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.
But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.
And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.
“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”
Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”
A version of this article appeared on Medscape.com.
. AI detected more than 99% of all skin cancers.
The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.
Skin cancer is the most common cancer in the United States; one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.
Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.
The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.
“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.
Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.
The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.
Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.
Limitations
The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.
But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.
And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.
“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”
Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”
A version of this article appeared on Medscape.com.
. AI detected more than 99% of all skin cancers.
The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.
Skin cancer is the most common cancer in the United States; one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.
Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.
The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.
“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.
Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.
The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.
Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.
Limitations
The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.
But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.
And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.
“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”
Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”
A version of this article appeared on Medscape.com.
FROM THE EADV CONGRESS
More evidence metformin may be neuroprotective
TOPLINE:
New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.
METHODOLOGY:
- Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
- The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
- The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.
TAKEAWAY:
- Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
- This association was largely independent of changes in A1c level and insulin usage.
IN PRACTICE:
The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.
SOURCE:
The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online in JAMA Network Open.
LIMITATIONS:
Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.
DISCLOSURES:
The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.
METHODOLOGY:
- Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
- The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
- The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.
TAKEAWAY:
- Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
- This association was largely independent of changes in A1c level and insulin usage.
IN PRACTICE:
The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.
SOURCE:
The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online in JAMA Network Open.
LIMITATIONS:
Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.
DISCLOSURES:
The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.
METHODOLOGY:
- Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
- The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
- The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.
TAKEAWAY:
- Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
- This association was largely independent of changes in A1c level and insulin usage.
IN PRACTICE:
The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.
SOURCE:
The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online in JAMA Network Open.
LIMITATIONS:
Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.
DISCLOSURES:
The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.
A version of this article first appeared on Medscape.com.
FDA OKs first ustekinumab biosimilar
The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.
Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.
“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”
Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.
Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.
The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.
Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.
The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.
Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.
“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”
Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.
Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.
The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.
Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.
The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.
Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.
“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”
Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.
Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.
The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.
Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.
The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.
A version of this article first appeared on Medscape.com.
Serious mental illness tied to 50% higher all-cause mortality risk after COVID
TOPLINE:
METHODOLOGY:
- Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
- The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
- Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
- Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).
TAKEAWAY:
- Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
- Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
- After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.
IN PRACTICE:
“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.
SOURCE:
Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.
LIMITATIONS:
COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.
DISCLOSURES:
One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
- The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
- Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
- Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).
TAKEAWAY:
- Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
- Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
- After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.
IN PRACTICE:
“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.
SOURCE:
Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.
LIMITATIONS:
COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.
DISCLOSURES:
One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
- The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
- Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
- Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).
TAKEAWAY:
- Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
- Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
- After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.
IN PRACTICE:
“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.
SOURCE:
Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.
LIMITATIONS:
COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.
DISCLOSURES:
One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.