Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

[email protected]

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

[email protected]

One in 15 patients who start dupilumab treatment may develop conjunctivitis during the first 6 months, most of which is manageable with ophthalmic treatments, results from large study of U.S. claims data showed.

“About 4 years after dupilumab’s approval, we’re interested in how conjunctivitis has played out in our daily clinical practice,” lead study investigator Maria C. Schneeweiss, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Drawing from two nationwide U.S. databases, MarketScan and Optum, Dr. Schneeweiss, of the department of dermatology at Brigham and Women’s Hospital, Boston, and colleagues sought to characterize the incidence of bacterial and nonbacterial conjunctivitis among 6,730 patients with AD who started treatment with either dupilumab, methotrexate, mycophenolate, or cyclosporine between March 2017 and January 2020. They also wanted to identify patient subgroups at increased or decreased risk of dupilumab-related conjunctivitis in clinical practice.

Of the 6,730 patients, 3,755 started treatment with dupilumab, while 2,010 started with methotrexate, 536 started with mycophenolate, and 429 started with cyclosporine. Using a new-user, active-comparator study design, the researchers identified patients with AD from both databases and selected three dupilumab cohorts: dupilumab versus methotrexate (MTX), dupilumab versus mycophenolate (MMF), and dupilumab versus cyclosporine (CsA). Follow-up lasted 6 months and 1:1 propensity score matching was used to account for conjunctivitis risk factor differences. Patients with a history of conjunctivitis were excluded from the study, except one subgroup limited to those with prior conjunctivitis.

Dr. Schneeweiss reported that the overall incidence rate of conjunctivitis within 6 months of treatment initiation was 6.6% in dupilumab users, or 1 in 15 patients, compared with 3.3% in MTX users, 4.2% in MMF users, and 2.8% in CsA users. The incidence rates for the different types of conjunctivitis were as follows:

• Bacterial conjunctivitis: 1.5% in dupilumab users versus 0.95% in MTX, 0.4% in MMF, and 0.7% in CsA users.
• Allergic conjunctivitis: 2.2% in dupilumab users versus 0.8% in MTX, 0.2% in MMF, and 1.6% in CsA users.
• Keratoconjunctivitis: 0.8% in dupilumab users versus 1.1% in MTX, 1.5% in MMF, and 0.5% in CsA users.

In addition, the rate of conjunctivitis requiring ophthalmic medication was 2.6% in dupilumab users versus 0.7% in MTX, 1% in MMF, and 0.5% in CsA users.

After the researchers applied 1:1 propensity score matching, they observed that the risk of conjunctivitis within 6 months of starting treatment was increased in dupilumab users versus MTX users (relative risk, 2.12), dupilumab versus MMF users (RR, 2.43), and dupilumab versus CsA users (RR, 1.83). Among dupilumab users, the risk of conjunctivitis requiring ophthalmic medication was increased six to eightfold, compared with those who used MTX, MMF or CsA. In addition, bacterial conjunctivitis was increased 1.6- to 4.0-fold, compared with those who used MTX, MMF or CsA, but the confidence intervals were wide and included the null, while allergic conjunctivitis was increased 2.7- to 7-fold when compared with those who used MTX and MMF.

In other findings, the risk of allergic conjunctivitis was similar between dupilumab and CsA users (RR, 1.14), and there was no increased risk of keratoconjunctivitis in dupilumab users, compared with those who used MTX, MMF, or CsA. The relative risk of conjunctivitis in those who used dupilumab was further increased when the analysis was limited to AD patients with comorbid asthma (RR, 2.86), those who used systemic glucocorticoids fewer than 30 days prior (RR, 2.88), and those age 65 and older (RR, 2.57), compared with those who used methotrexate.

“Compared to AD patients who received treatment with other systemic agents, dupilumab treatment doubled the risk of conjunctivitis in clinical practice,” Dr. Schneeweiss concluded. “Risk factors that further increase the risk include comorbid asthma, use of systemic corticosteroids, and older age. It should be noted that conjunctivitis does not require treatment discontinuation and is manageable with ophthalmic medications.”

Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study, said that the work “verifies what we see clinically: that conjunctivitis is increased among dupilumab users even when it is compared to immunosuppressive agents used to treat other conditions. Because the study is retrospective, one cannot assume all diagnosis of types of conjunctivitis or even of skin disease is entirely accurate. But, with the large numbers of claims looked at and compared, one would think its conclusions are accurate.”

Dr. Schneeweiss reported having no relevant financial disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for Amgen, AbbVie, Arcutis, Brickell, Candescent, Cassiopeia, Dermavant, Galderma, Janssen, Forte, Incyte, MC-2, Lilly, Novartis, Novan, Ortho Dermatologics, Revance, Sun Pharma, UCB, and Vyne.

[email protected]

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

[email protected]

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

[email protected]

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

[email protected]

Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

pixologicstudio/Thinkstock

“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

pixologicstudio/Thinkstock

“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

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“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Public health precautions meant to reduce the spread of COVID-19 may have had an unintended but happy side effect.

They may also have benefited individuals who have chronic obstructive pulmonary disease (COPD), according to a new study.

During the pandemic, admissions for COPD flare-ups dropped dramatically – by 53% – at University of Maryland Medical System hospitals.

Researchers at the university suspect this was the result of a drop in circulating seasonal respiratory viruses, such as influenza. They theorized that stay-at-home orders, social distancing, mask mandates, and strict limits on large gatherings reduced exposure not only to COVID but also to other respiratory infections.

“Our study shows there’s a silver lining to the behavior changes beyond protecting against COVID-19,” said senior author Robert Reed, MD, a pulmonologist and professor of medicine.

COPD is a group of lung diseases that worsen over time and make it hard to breathe. Before the pandemic, they were the fourth-leading cause of death worldwide, commonly triggered by tobacco smoke and dirty air. Nearly half of flare-ups are caused by seasonal respiratory viruses.

For the study, the researchers analyzed data from 13 UMMS hospitals, comparing weekly admissions for COPD in 2018 and 2019, with admissions after April 1, 2020, when COVID-19 public health measures were introduced. Investigators chose the same six-month period in each year for comparison – April 1 to Sept. 30.

The findings were matched against U.S. federal data on respiratory viral trends between Jan. 1, 2018, and Oct. 1, 2020.

As significant as was the system’s 53% drop in COPD admissions during the pandemic, there was also a 36% decline in weekly admissions for such serious conditions as congestive heart failure, diabetes and heart attack, said co–lead author Jennifer So, MD. She’s an assistant professor of medicine and COPD specialist.

The researchers warned that a full return to normal may again expose COPD patients to the familiar seasonal triggers.

“If we completely eliminate masks and distancing during cold and flu season, we’ll allow all those viruses that have been effectively suppressed to come raging back,” Dr. Reed said in a university news release. “There could be a lot of illness.”

He noted that the study did not assess which measures tamed seasonal viruses. But, Dr. Reed added, “a simple thing like wearing a mask while riding on public transit or working from home when you’re sick with a cold could go a long way to reduce virus exposure.”

Dr. So said it is a cultural norm in her native South Korea to wear masks during the winter.

“The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease,” she said in the release.

The findings were recently published in the preprint server medRxiv and have not yet been peer reviewed.

The U.S. Centers for Disease Control and Prevention has more information on COVID-19 and chronic lung diseases.

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

Public health precautions meant to reduce the spread of COVID-19 may have had an unintended but happy side effect.

They may also have benefited individuals who have chronic obstructive pulmonary disease (COPD), according to a new study.

During the pandemic, admissions for COPD flare-ups dropped dramatically – by 53% – at University of Maryland Medical System hospitals.

Researchers at the university suspect this was the result of a drop in circulating seasonal respiratory viruses, such as influenza. They theorized that stay-at-home orders, social distancing, mask mandates, and strict limits on large gatherings reduced exposure not only to COVID but also to other respiratory infections.

“Our study shows there’s a silver lining to the behavior changes beyond protecting against COVID-19,” said senior author Robert Reed, MD, a pulmonologist and professor of medicine.

COPD is a group of lung diseases that worsen over time and make it hard to breathe. Before the pandemic, they were the fourth-leading cause of death worldwide, commonly triggered by tobacco smoke and dirty air. Nearly half of flare-ups are caused by seasonal respiratory viruses.

For the study, the researchers analyzed data from 13 UMMS hospitals, comparing weekly admissions for COPD in 2018 and 2019, with admissions after April 1, 2020, when COVID-19 public health measures were introduced. Investigators chose the same six-month period in each year for comparison – April 1 to Sept. 30.

The findings were matched against U.S. federal data on respiratory viral trends between Jan. 1, 2018, and Oct. 1, 2020.

As significant as was the system’s 53% drop in COPD admissions during the pandemic, there was also a 36% decline in weekly admissions for such serious conditions as congestive heart failure, diabetes and heart attack, said co–lead author Jennifer So, MD. She’s an assistant professor of medicine and COPD specialist.

The researchers warned that a full return to normal may again expose COPD patients to the familiar seasonal triggers.

“If we completely eliminate masks and distancing during cold and flu season, we’ll allow all those viruses that have been effectively suppressed to come raging back,” Dr. Reed said in a university news release. “There could be a lot of illness.”

He noted that the study did not assess which measures tamed seasonal viruses. But, Dr. Reed added, “a simple thing like wearing a mask while riding on public transit or working from home when you’re sick with a cold could go a long way to reduce virus exposure.”

Dr. So said it is a cultural norm in her native South Korea to wear masks during the winter.

“The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease,” she said in the release.

The findings were recently published in the preprint server medRxiv and have not yet been peer reviewed.

The U.S. Centers for Disease Control and Prevention has more information on COVID-19 and chronic lung diseases.

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

Public health precautions meant to reduce the spread of COVID-19 may have had an unintended but happy side effect.

They may also have benefited individuals who have chronic obstructive pulmonary disease (COPD), according to a new study.

During the pandemic, admissions for COPD flare-ups dropped dramatically – by 53% – at University of Maryland Medical System hospitals.

Researchers at the university suspect this was the result of a drop in circulating seasonal respiratory viruses, such as influenza. They theorized that stay-at-home orders, social distancing, mask mandates, and strict limits on large gatherings reduced exposure not only to COVID but also to other respiratory infections.

“Our study shows there’s a silver lining to the behavior changes beyond protecting against COVID-19,” said senior author Robert Reed, MD, a pulmonologist and professor of medicine.

COPD is a group of lung diseases that worsen over time and make it hard to breathe. Before the pandemic, they were the fourth-leading cause of death worldwide, commonly triggered by tobacco smoke and dirty air. Nearly half of flare-ups are caused by seasonal respiratory viruses.

For the study, the researchers analyzed data from 13 UMMS hospitals, comparing weekly admissions for COPD in 2018 and 2019, with admissions after April 1, 2020, when COVID-19 public health measures were introduced. Investigators chose the same six-month period in each year for comparison – April 1 to Sept. 30.

The findings were matched against U.S. federal data on respiratory viral trends between Jan. 1, 2018, and Oct. 1, 2020.

As significant as was the system’s 53% drop in COPD admissions during the pandemic, there was also a 36% decline in weekly admissions for such serious conditions as congestive heart failure, diabetes and heart attack, said co–lead author Jennifer So, MD. She’s an assistant professor of medicine and COPD specialist.

The researchers warned that a full return to normal may again expose COPD patients to the familiar seasonal triggers.

“If we completely eliminate masks and distancing during cold and flu season, we’ll allow all those viruses that have been effectively suppressed to come raging back,” Dr. Reed said in a university news release. “There could be a lot of illness.”

He noted that the study did not assess which measures tamed seasonal viruses. But, Dr. Reed added, “a simple thing like wearing a mask while riding on public transit or working from home when you’re sick with a cold could go a long way to reduce virus exposure.”

Dr. So said it is a cultural norm in her native South Korea to wear masks during the winter.

“The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease,” she said in the release.

The findings were recently published in the preprint server medRxiv and have not yet been peer reviewed.

The U.S. Centers for Disease Control and Prevention has more information on COVID-19 and chronic lung diseases.

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