Federal Practitioner

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

A new analysis has shown disparities in cardiovascular risk factors between Black and White adults in the United States, disparities that may be largely attributable to social determinants of health.

Investigators analyzed 20 years of data on over 50,500 U.S. adults drawn from the National Health and Nutrition Examination Surveys (NHANES) and found that, in the overall population, body mass index and hemoglobin A1c were significantly increased between 1999 and 2018, while serum total cholesterol and cigarette smoking were significantly decreased. Mean systolic blood pressure decreased between 1999 and 2010, but then increased after 2010.

The mean age- and sex-adjusted estimated 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was consistently higher in Black participants vs. White participants, but the difference was attenuated after further adjusting for education, income, home ownership, employment, health insurance, and access to health care.

“These findings are helpful to guide the development of national public health policies for targeted interventions aimed at eliminating health disparities,” Jiang He, MD, PhD, Joseph S. Copes Chair and professor of epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, said in an interview.

“Interventions on social determinants of cardiovascular health should be tested in rigorous designed intervention trials,” said Dr. He, director of the Tulane University Translational Science Institute.

The study was published online Oct. 5 in JAMA.
 

‘Flattened’ CVD mortality?

Recent data show that the CVD mortality rate flattened, while the total number of cardiovascular deaths increased in the U.S. general population from 2010 to 2018, “but the reasons for this deceleration in the decline of CVD mortality are not entirely understood,” Dr. He said.

Moreover, “racial and ethnic differences in CVD mortality persist in the U.S. general population [but] the secular trends of cardiovascular risk factors among U.S. subpopulations with various racial and ethnic backgrounds and socioeconomic status are [also] not well understood,” he added. The effects of social determinants of health, such as education, income, home ownership, employment, health insurance, and access to health care on racial/ethnic differences in CVD risk, “are not well documented.”

To investigate these questions, the researchers drew on data from NHANES, a series of cross-sectional surveys in nationally representative samples of the U.S. population aged 20 years and older. The surveys are conducted in 2-year cycles and include data from 10 cycles conducted from 1999-2000 to 2017-2018 (n = 50,571, mean age 49.0-51.8 years; 48.2%-51.3% female).

Every 2 years, participants provided sociodemographic information, including age, race/ethnicity, sex, education, income, employment, housing, health insurance, and access to health care, as well as medical history and medication use. They underwent a physical examination that included weight and height, blood pressure, lipid levels, plasma glucose, and hemoglobin A1c.
 

Social determinants of health

Between 1999-2000 and 2017-2018, age- and sex-adjusted mean BMI and hemoglobin A1c increased, while mean serum total cholesterol and prevalence of smoking decreased (all P < .001).

Participants with at least a college education or high family income had “consistently lower levels” of cardiovascular risk factors. And although the mean age- and sex-adjusted 10-year risk for ASCVD was significantly higher in non-Hispanic Black vs. non-Hispanic White participants (difference, 1.4% [1.0%-1.7%] in 1999-2008 and 2.0% [1.7%-2.4%] in 2009-2018), the difference was attenuated (by –0.3% in 1999-2008 and 0.7% in 2009-2018) after the researchers further adjusted for education, income, home ownership, employment, health insurance, and access to health care.

The differences in cardiovascular risk factors between Black and White participants “may have been moderated by social determinants of health,” the authors noted.
 

Provide appropriate education

Commenting on the study in an interview, Mary Ann McLaughlin, MD, MPH, associate professor of medicine, cardiology, Icahn School of Medicine at Mount Sinai, New York, pointed out that two important cardiovascular risk factors associated with being overweight – hypertension and diabetes – remained higher in the Black population compared with the White population in this analysis.

“Physicians and health care systems should provide appropriate education and resources regarding risk factor modification regarding diet, exercise, and blood pressure control,” advised Dr. McLaughlin, who was not involved with the study.

“Importantly, smoking rates and cholesterol levels are lower in the Black population, compared to the White population, when adjusted for many important socioeconomic factors,” she pointed out.

Dr. McLaughlin added that other “important social determinants of health, such as neighborhood and access to healthy food, were not measured and should be addressed by physicians when optimizing cardiovascular risk.”

The research reported in this publication was supported by the National Heart, Lung, and Blood Institute and by the National Institute of General Medical Sciences. One of the researchers, Joshua D. Bundy, PhD, was supported by a grant from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. He and the other coauthors and Dr. McLaughlin reported no relevant financial relationships.
 

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

A new analysis has shown disparities in cardiovascular risk factors between Black and White adults in the United States, disparities that may be largely attributable to social determinants of health.

Investigators analyzed 20 years of data on over 50,500 U.S. adults drawn from the National Health and Nutrition Examination Surveys (NHANES) and found that, in the overall population, body mass index and hemoglobin A1c were significantly increased between 1999 and 2018, while serum total cholesterol and cigarette smoking were significantly decreased. Mean systolic blood pressure decreased between 1999 and 2010, but then increased after 2010.

The mean age- and sex-adjusted estimated 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was consistently higher in Black participants vs. White participants, but the difference was attenuated after further adjusting for education, income, home ownership, employment, health insurance, and access to health care.

“These findings are helpful to guide the development of national public health policies for targeted interventions aimed at eliminating health disparities,” Jiang He, MD, PhD, Joseph S. Copes Chair and professor of epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, said in an interview.

“Interventions on social determinants of cardiovascular health should be tested in rigorous designed intervention trials,” said Dr. He, director of the Tulane University Translational Science Institute.

The study was published online Oct. 5 in JAMA.
 

‘Flattened’ CVD mortality?

Recent data show that the CVD mortality rate flattened, while the total number of cardiovascular deaths increased in the U.S. general population from 2010 to 2018, “but the reasons for this deceleration in the decline of CVD mortality are not entirely understood,” Dr. He said.

Moreover, “racial and ethnic differences in CVD mortality persist in the U.S. general population [but] the secular trends of cardiovascular risk factors among U.S. subpopulations with various racial and ethnic backgrounds and socioeconomic status are [also] not well understood,” he added. The effects of social determinants of health, such as education, income, home ownership, employment, health insurance, and access to health care on racial/ethnic differences in CVD risk, “are not well documented.”

To investigate these questions, the researchers drew on data from NHANES, a series of cross-sectional surveys in nationally representative samples of the U.S. population aged 20 years and older. The surveys are conducted in 2-year cycles and include data from 10 cycles conducted from 1999-2000 to 2017-2018 (n = 50,571, mean age 49.0-51.8 years; 48.2%-51.3% female).

Every 2 years, participants provided sociodemographic information, including age, race/ethnicity, sex, education, income, employment, housing, health insurance, and access to health care, as well as medical history and medication use. They underwent a physical examination that included weight and height, blood pressure, lipid levels, plasma glucose, and hemoglobin A1c.
 

Social determinants of health

Between 1999-2000 and 2017-2018, age- and sex-adjusted mean BMI and hemoglobin A1c increased, while mean serum total cholesterol and prevalence of smoking decreased (all P < .001).

Participants with at least a college education or high family income had “consistently lower levels” of cardiovascular risk factors. And although the mean age- and sex-adjusted 10-year risk for ASCVD was significantly higher in non-Hispanic Black vs. non-Hispanic White participants (difference, 1.4% [1.0%-1.7%] in 1999-2008 and 2.0% [1.7%-2.4%] in 2009-2018), the difference was attenuated (by –0.3% in 1999-2008 and 0.7% in 2009-2018) after the researchers further adjusted for education, income, home ownership, employment, health insurance, and access to health care.

The differences in cardiovascular risk factors between Black and White participants “may have been moderated by social determinants of health,” the authors noted.
 

Provide appropriate education

Commenting on the study in an interview, Mary Ann McLaughlin, MD, MPH, associate professor of medicine, cardiology, Icahn School of Medicine at Mount Sinai, New York, pointed out that two important cardiovascular risk factors associated with being overweight – hypertension and diabetes – remained higher in the Black population compared with the White population in this analysis.

“Physicians and health care systems should provide appropriate education and resources regarding risk factor modification regarding diet, exercise, and blood pressure control,” advised Dr. McLaughlin, who was not involved with the study.

“Importantly, smoking rates and cholesterol levels are lower in the Black population, compared to the White population, when adjusted for many important socioeconomic factors,” she pointed out.

Dr. McLaughlin added that other “important social determinants of health, such as neighborhood and access to healthy food, were not measured and should be addressed by physicians when optimizing cardiovascular risk.”

The research reported in this publication was supported by the National Heart, Lung, and Blood Institute and by the National Institute of General Medical Sciences. One of the researchers, Joshua D. Bundy, PhD, was supported by a grant from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. He and the other coauthors and Dr. McLaughlin reported no relevant financial relationships.
 

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

A new analysis has shown disparities in cardiovascular risk factors between Black and White adults in the United States, disparities that may be largely attributable to social determinants of health.

Investigators analyzed 20 years of data on over 50,500 U.S. adults drawn from the National Health and Nutrition Examination Surveys (NHANES) and found that, in the overall population, body mass index and hemoglobin A1c were significantly increased between 1999 and 2018, while serum total cholesterol and cigarette smoking were significantly decreased. Mean systolic blood pressure decreased between 1999 and 2010, but then increased after 2010.

The mean age- and sex-adjusted estimated 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was consistently higher in Black participants vs. White participants, but the difference was attenuated after further adjusting for education, income, home ownership, employment, health insurance, and access to health care.

“These findings are helpful to guide the development of national public health policies for targeted interventions aimed at eliminating health disparities,” Jiang He, MD, PhD, Joseph S. Copes Chair and professor of epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, said in an interview.

“Interventions on social determinants of cardiovascular health should be tested in rigorous designed intervention trials,” said Dr. He, director of the Tulane University Translational Science Institute.

The study was published online Oct. 5 in JAMA.
 

‘Flattened’ CVD mortality?

Recent data show that the CVD mortality rate flattened, while the total number of cardiovascular deaths increased in the U.S. general population from 2010 to 2018, “but the reasons for this deceleration in the decline of CVD mortality are not entirely understood,” Dr. He said.

Moreover, “racial and ethnic differences in CVD mortality persist in the U.S. general population [but] the secular trends of cardiovascular risk factors among U.S. subpopulations with various racial and ethnic backgrounds and socioeconomic status are [also] not well understood,” he added. The effects of social determinants of health, such as education, income, home ownership, employment, health insurance, and access to health care on racial/ethnic differences in CVD risk, “are not well documented.”

To investigate these questions, the researchers drew on data from NHANES, a series of cross-sectional surveys in nationally representative samples of the U.S. population aged 20 years and older. The surveys are conducted in 2-year cycles and include data from 10 cycles conducted from 1999-2000 to 2017-2018 (n = 50,571, mean age 49.0-51.8 years; 48.2%-51.3% female).

Every 2 years, participants provided sociodemographic information, including age, race/ethnicity, sex, education, income, employment, housing, health insurance, and access to health care, as well as medical history and medication use. They underwent a physical examination that included weight and height, blood pressure, lipid levels, plasma glucose, and hemoglobin A1c.
 

Social determinants of health

Between 1999-2000 and 2017-2018, age- and sex-adjusted mean BMI and hemoglobin A1c increased, while mean serum total cholesterol and prevalence of smoking decreased (all P < .001).

Participants with at least a college education or high family income had “consistently lower levels” of cardiovascular risk factors. And although the mean age- and sex-adjusted 10-year risk for ASCVD was significantly higher in non-Hispanic Black vs. non-Hispanic White participants (difference, 1.4% [1.0%-1.7%] in 1999-2008 and 2.0% [1.7%-2.4%] in 2009-2018), the difference was attenuated (by –0.3% in 1999-2008 and 0.7% in 2009-2018) after the researchers further adjusted for education, income, home ownership, employment, health insurance, and access to health care.

The differences in cardiovascular risk factors between Black and White participants “may have been moderated by social determinants of health,” the authors noted.
 

Provide appropriate education

Commenting on the study in an interview, Mary Ann McLaughlin, MD, MPH, associate professor of medicine, cardiology, Icahn School of Medicine at Mount Sinai, New York, pointed out that two important cardiovascular risk factors associated with being overweight – hypertension and diabetes – remained higher in the Black population compared with the White population in this analysis.

“Physicians and health care systems should provide appropriate education and resources regarding risk factor modification regarding diet, exercise, and blood pressure control,” advised Dr. McLaughlin, who was not involved with the study.

“Importantly, smoking rates and cholesterol levels are lower in the Black population, compared to the White population, when adjusted for many important socioeconomic factors,” she pointed out.

Dr. McLaughlin added that other “important social determinants of health, such as neighborhood and access to healthy food, were not measured and should be addressed by physicians when optimizing cardiovascular risk.”

The research reported in this publication was supported by the National Heart, Lung, and Blood Institute and by the National Institute of General Medical Sciences. One of the researchers, Joshua D. Bundy, PhD, was supported by a grant from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. He and the other coauthors and Dr. McLaughlin reported no relevant financial relationships.
 

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

Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.

Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.

Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.

Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.

The study was published online October 15 in JAMA Network Open.
 

Opioid deaths

Centers for Disease Control and Prevention data show more than 93,000 individuals in the United States died from a drug overdose in 2020, a 29.4% increase from the previous year. Of those deaths, 69,710 involved opioids.

Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.

The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.

Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.

Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.

In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.

While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
 

A different picture of misuse

The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.

Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).

Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).

It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).

There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.

“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.

“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.

Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
 

‘Don’t exaggerate concerns’

Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.

The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.

The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.

Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.

“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.

“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
 

Symptom of inadequate access?

Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”

“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.

A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.

In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”

The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.

“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.

The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.

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

Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.

Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.

Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.

Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.

The study was published online October 15 in JAMA Network Open.
 

Opioid deaths

Centers for Disease Control and Prevention data show more than 93,000 individuals in the United States died from a drug overdose in 2020, a 29.4% increase from the previous year. Of those deaths, 69,710 involved opioids.

Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.

The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.

Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.

Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.

In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.

While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
 

A different picture of misuse

The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.

Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).

Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).

It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).

There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.

“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.

“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.

Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
 

‘Don’t exaggerate concerns’

Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.

The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.

The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.

Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.

“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.

“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
 

Symptom of inadequate access?

Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”

“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.

A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.

In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”

The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.

“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.

The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.

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

Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.

Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.

Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.

Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.

The study was published online October 15 in JAMA Network Open.
 

Opioid deaths

Centers for Disease Control and Prevention data show more than 93,000 individuals in the United States died from a drug overdose in 2020, a 29.4% increase from the previous year. Of those deaths, 69,710 involved opioids.

Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.

The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.

Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.

Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.

In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.

While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
 

A different picture of misuse

The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.

Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).

Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).

It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).

There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.

“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.

“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.

Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
 

‘Don’t exaggerate concerns’

Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.

The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.

The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.

Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.

“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.

“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
 

Symptom of inadequate access?

Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”

“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.

A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.

In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”

The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.

“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.

The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.

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

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

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

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

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

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).