Jeff Craven

Attendees at HM20 Virtual can expect some changes when it comes to how hospitalists should refer to and manage pneumonia, according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.

Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.

CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.

Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.

One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.

“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.

The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.

Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.

Dr. Bonsall reported no relevant financial disclosures.

Updates in Pneumonia

Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.

Attendees at HM20 Virtual can expect some changes when it comes to how hospitalists should refer to and manage pneumonia, according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.

Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.

CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.

Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.

One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.

“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.

The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.

Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.

Dr. Bonsall reported no relevant financial disclosures.

Updates in Pneumonia

Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.

Attendees at HM20 Virtual can expect some changes when it comes to how hospitalists should refer to and manage pneumonia, according to Joanna M. Bonsall, MD, PhD, SFHM, chief of hospital medicine at Grady Memorial Hospital and associate professor of medicine at Emory University, both in Atlanta.

Last year, the American Thoracic Society and the Infectious Diseases Society of America updated their clinical guidelines on community-acquired pneumonia (CAP) for the first time since 2007. The guidelines were published in the Oct. 1, 2019 issue of the American Journal of Respiratory and Critical Care Medicine.

CAP is one of the most common reasons for hospitalization in the United States, and it is estimated that CAP comprises over 4.5 million outpatient and ED visits each year, according to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey in 2009-2010. It is also the most common cause of death from infection disease, according to the Centers for Disease Control and Prevention.

Dr. Bonsall will present “Updates in Pneumonia” at HM20 Virtual, the virtual annual meeting of the Society of Hospital Medicine; a live question-and-answer session will be held online Aug. 20. In her session, Dr. Bonsall said she plans to cover the new ATS/IDSA guidelines for CAP, which will include what initial testing to order, which empiric antibiotics to use, and how to manage patients at risk for resistant organisms, formerly known as health care–associated pneumonia (HCAP). Dr. Bonsall also will outline the evidence for use of steroids, especially in cases of severe pneumonia, and review the 2016 ATS/IDSA guidelines for hospital-acquired pneumonia with a focus on antibiotic selection.

One major change for 2019: The ATS/IDSA CAP guideline authors issued a strong recommendation to abandon use of the term HCAP as a “distinct clinical entity” when considering antibiotics for patients with CAP. In addition, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa should only be empirically covered in patients with CAP if they present with locally validated risk factors for either pathogen, according to the guidelines.

“Order pretreatment testing based on severity of illness as well as risk factors for drug-resistant pathogens,” Dr. Bonsall said. Hospitalists also should avoid using procalcitonin levels as a benchmark for whether a patient should be started on antibiotics. Once the recommended antibiotic treatment has been initiated, attendees should use culture results to narrow down the possibilities, especially in cases of drug-resistant pathogens.

The ATS/IDSA guidelines also state that corticosteroids should not be routinely used for patients with nonsevere CAP, but attendees should also be aware of the limitations and interpretations of the evidence, Dr. Bonsall said. Avoiding routine corticosteroid use in patients with severe CAP or in patients with severe influenza pneumonia carries a conditional recommendation with a moderate and low quality of evidence, respectively. In general, cases of CAP should be treated for no more than 5 days, or 3 days of treatment after the patient becomes clinically stable.

Attendees at HM20 Virtual should walk away from the session knowing what testing is necessary and what testing is unnecessary, and how to reduce antibiotic exposure for both broad spectrum use and duration. “At the end of the session, you should feel comfortable using both the CAP and HAP guidelines,” Dr. Bonsall said.

Dr. Bonsall reported no relevant financial disclosures.

Updates in Pneumonia

Live Q&A: Thursday, Aug. 20, 2:15 p.m to 3:15 p.m.

Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

Older individuals had a higher risk of complications 30 days after undergoing a colonoscopy as an outpatient procedure compared with a younger group of colorectal cancer screening–eligible individuals, according to recent research published in JAMA Network Open.

Natalia Causada-Calo, MD, MSc, division of gastroenterology, at St. Michael’s Hospital, University of Toronto, and colleagues performed a retrospective cohort study of 38,069 patients in Ontario administrative databases who underwent colonoscopy between April 2008 and September 2017. The patients included were older than 50 years (mean age, 65.2 years) with a majority (73.1%) undergoing their first colonoscopy. Those with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. Researchers divided patients into groups based on age, placing patients aged 50-74 years into a colorectal cancer–screening eligible group (30,443 patients), and individuals 75 years or older into an “older cohort” (7,627 patients). Dr. Causada-Calo and colleagues analyzed 30-day admission to hospital or emergency department, and also examined 30-day all-cause mortality and incidence of colorectal cancer.

Among individuals in the older cohort, 515 of 7,627 patients (6.8%) experienced complications after colonoscopy compared with 795 of 30,443 patients (2.6%) in the screening-eligible cohort (P less than .001). Older age was an independent risk factor for postcolonoscopy complications, with individuals older than 75 years having twofold greater odds of complications after colonoscopy (odds ratio, 2.3; 95% confidence interval, 2.0-2.6) compared with individuals aged 50-74 years.

Other independent risk factors for complications included liver disease (OR, 4.7; 95% CI, 3.5-6.5), heart failure (OR, 3.4; 95% CI, 2.5-4.6), smoking history (OR, 3.2; 95% CI, 2.4-4.3), obesity (OR, 2.3; 95% CI, 1.2-4.2), chronic kidney disease (OR, 1.8; 95% CI, 1.1-3.0), cardiac arrhythmia (OR, 1.7; 95% CI, 1.2-2.2), anemia (OR, 1.4; 95% CI, 1.2-1.7), and hypertension (OR, 1.2; 95% CI, 1.0-1.5). Individuals who had previously undergone colonoscopy had a lower risk of complications after the procedure (OR, 0.9; 95% CI, 0.7-1.0).

There was a significantly higher incidence of colorectal cancer treated with surgery in the older group (119 of 7,626; 1.6%) compared with the younger (144 of 30,443; 0.5%) group (P less than .001). Mortality from any cause was also significantly higher in the older group (20 patients; 0.2%) compared with the younger (39 patients; 0.1%) group (P less than .001).

“In accordance with our findings, the decision to perform colonoscopy should be considered carefully in older patients, particularly in the presence of comorbidities,” Dr. Causada-Calo and colleagues wrote.

Aasma Shaukat, MD, MPH, GI section chief at Minneapolis VA Health Care System and professor of medicine at University of Minnesota, said in an interview that screening colonoscopy in a population older than 75 years should be an individualized discussion with a patient who has minimal comorbidities, and the decision to move forward with a colonoscopy should be considered only if a patient’s life expectancy is at least 10 years.

“This study shows that diagnostic colonoscopy is associated with high risk of complications and quantifies the risk, to frame the discussion with the patient about going forward,” she said. “Colorectal cancers are slow growing. In individuals age 75 and older, competing health risks and risk of the colonoscopy often outweigh the small benefit they may derive. Older individuals should thus focus on other health priorities.”

Physicians should make their older patients aware that there is a risk for serious adverse events, including death, which increases after age 75. “[The] risk-benefit ratio for performing colonoscopy needs to carefully weighed,” Dr. Shaukat said. “[T]he patient should be presented with options, including the option of no screening.”

The American Cancer Society advocates “for individualized decision-making regarding screening for individuals after 75 but [does] not give any firm recommendations,” while the U.S. Preventive Services Task Force noted in its recommendations on colorectal cancer screening that the “harms are large and benefits are small” after 75 years of age, and choice to screen for colorectal cancer in that age group is an individual one, Dr. Shaukat said.

Robert A. Smith, PhD, senior vice president of cancer screening at the American Cancer Society, said in an interview that while colonoscopy is the dominant screening test for colorectal cancer, it is not known how often physicians and their older patients discuss noninvasive colorectal cancer screening methods. Noninvasive screening methods such as a high-sensitivity stool test should be a consideration even for older adults with mild chronic conditions, “especially if they have a history of screening with negative results,” he said. “[A] history of regular screening with normal test results should be a basis for considering cessation of screening after age 75, or at least transition to a test with lower risks of complications.”

Future research in this area could use a hybrid model of screening, such as using different tests among various age groups or risk groups, to see whether an invasive or noninvasive method would lower a complication rate, Dr. Smith said. “Further, we need to have a greater understanding of when individuals can confidently stop getting screened, based on their underlying risk and history of prior screening results,” he noted.

Dr. Shaukat said future studies should focus on randomized trials for individuals 75 years and older to assess the benefits and harms of screening, “[d]eveloping risk stratification tools that factor in an individual’s risk of colon cancer, their life expectancy, and guide individualized decision making to undergo screening.”

Dr. Armstrong is the chair of the National Colon Cancer Screening Network for the Canadian Partnership Against Cancer and the past president of the Canadian Association of Gastroenterology. Dr. Albashir has received honoraria and speaker fees from Janssen, and grants from AbbVie and ATGen. Dr. Shaukat and Dr. Smith report no relevant conflicts of interest.

SOURCE: Causada-Calo N et al. JAMA Netw Open. 2020;3(6):e208958.

Older individuals had a higher risk of complications 30 days after undergoing a colonoscopy as an outpatient procedure compared with a younger group of colorectal cancer screening–eligible individuals, according to recent research published in JAMA Network Open.

Natalia Causada-Calo, MD, MSc, division of gastroenterology, at St. Michael’s Hospital, University of Toronto, and colleagues performed a retrospective cohort study of 38,069 patients in Ontario administrative databases who underwent colonoscopy between April 2008 and September 2017. The patients included were older than 50 years (mean age, 65.2 years) with a majority (73.1%) undergoing their first colonoscopy. Those with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. Researchers divided patients into groups based on age, placing patients aged 50-74 years into a colorectal cancer–screening eligible group (30,443 patients), and individuals 75 years or older into an “older cohort” (7,627 patients). Dr. Causada-Calo and colleagues analyzed 30-day admission to hospital or emergency department, and also examined 30-day all-cause mortality and incidence of colorectal cancer.

Among individuals in the older cohort, 515 of 7,627 patients (6.8%) experienced complications after colonoscopy compared with 795 of 30,443 patients (2.6%) in the screening-eligible cohort (P less than .001). Older age was an independent risk factor for postcolonoscopy complications, with individuals older than 75 years having twofold greater odds of complications after colonoscopy (odds ratio, 2.3; 95% confidence interval, 2.0-2.6) compared with individuals aged 50-74 years.

Other independent risk factors for complications included liver disease (OR, 4.7; 95% CI, 3.5-6.5), heart failure (OR, 3.4; 95% CI, 2.5-4.6), smoking history (OR, 3.2; 95% CI, 2.4-4.3), obesity (OR, 2.3; 95% CI, 1.2-4.2), chronic kidney disease (OR, 1.8; 95% CI, 1.1-3.0), cardiac arrhythmia (OR, 1.7; 95% CI, 1.2-2.2), anemia (OR, 1.4; 95% CI, 1.2-1.7), and hypertension (OR, 1.2; 95% CI, 1.0-1.5). Individuals who had previously undergone colonoscopy had a lower risk of complications after the procedure (OR, 0.9; 95% CI, 0.7-1.0).

There was a significantly higher incidence of colorectal cancer treated with surgery in the older group (119 of 7,626; 1.6%) compared with the younger (144 of 30,443; 0.5%) group (P less than .001). Mortality from any cause was also significantly higher in the older group (20 patients; 0.2%) compared with the younger (39 patients; 0.1%) group (P less than .001).

“In accordance with our findings, the decision to perform colonoscopy should be considered carefully in older patients, particularly in the presence of comorbidities,” Dr. Causada-Calo and colleagues wrote.

Aasma Shaukat, MD, MPH, GI section chief at Minneapolis VA Health Care System and professor of medicine at University of Minnesota, said in an interview that screening colonoscopy in a population older than 75 years should be an individualized discussion with a patient who has minimal comorbidities, and the decision to move forward with a colonoscopy should be considered only if a patient’s life expectancy is at least 10 years.

“This study shows that diagnostic colonoscopy is associated with high risk of complications and quantifies the risk, to frame the discussion with the patient about going forward,” she said. “Colorectal cancers are slow growing. In individuals age 75 and older, competing health risks and risk of the colonoscopy often outweigh the small benefit they may derive. Older individuals should thus focus on other health priorities.”

Physicians should make their older patients aware that there is a risk for serious adverse events, including death, which increases after age 75. “[The] risk-benefit ratio for performing colonoscopy needs to carefully weighed,” Dr. Shaukat said. “[T]he patient should be presented with options, including the option of no screening.”

The American Cancer Society advocates “for individualized decision-making regarding screening for individuals after 75 but [does] not give any firm recommendations,” while the U.S. Preventive Services Task Force noted in its recommendations on colorectal cancer screening that the “harms are large and benefits are small” after 75 years of age, and choice to screen for colorectal cancer in that age group is an individual one, Dr. Shaukat said.

Robert A. Smith, PhD, senior vice president of cancer screening at the American Cancer Society, said in an interview that while colonoscopy is the dominant screening test for colorectal cancer, it is not known how often physicians and their older patients discuss noninvasive colorectal cancer screening methods. Noninvasive screening methods such as a high-sensitivity stool test should be a consideration even for older adults with mild chronic conditions, “especially if they have a history of screening with negative results,” he said. “[A] history of regular screening with normal test results should be a basis for considering cessation of screening after age 75, or at least transition to a test with lower risks of complications.”

Future research in this area could use a hybrid model of screening, such as using different tests among various age groups or risk groups, to see whether an invasive or noninvasive method would lower a complication rate, Dr. Smith said. “Further, we need to have a greater understanding of when individuals can confidently stop getting screened, based on their underlying risk and history of prior screening results,” he noted.

Dr. Shaukat said future studies should focus on randomized trials for individuals 75 years and older to assess the benefits and harms of screening, “[d]eveloping risk stratification tools that factor in an individual’s risk of colon cancer, their life expectancy, and guide individualized decision making to undergo screening.”

Dr. Armstrong is the chair of the National Colon Cancer Screening Network for the Canadian Partnership Against Cancer and the past president of the Canadian Association of Gastroenterology. Dr. Albashir has received honoraria and speaker fees from Janssen, and grants from AbbVie and ATGen. Dr. Shaukat and Dr. Smith report no relevant conflicts of interest.

SOURCE: Causada-Calo N et al. JAMA Netw Open. 2020;3(6):e208958.

Older individuals had a higher risk of complications 30 days after undergoing a colonoscopy as an outpatient procedure compared with a younger group of colorectal cancer screening–eligible individuals, according to recent research published in JAMA Network Open.

Natalia Causada-Calo, MD, MSc, division of gastroenterology, at St. Michael’s Hospital, University of Toronto, and colleagues performed a retrospective cohort study of 38,069 patients in Ontario administrative databases who underwent colonoscopy between April 2008 and September 2017. The patients included were older than 50 years (mean age, 65.2 years) with a majority (73.1%) undergoing their first colonoscopy. Those with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. Researchers divided patients into groups based on age, placing patients aged 50-74 years into a colorectal cancer–screening eligible group (30,443 patients), and individuals 75 years or older into an “older cohort” (7,627 patients). Dr. Causada-Calo and colleagues analyzed 30-day admission to hospital or emergency department, and also examined 30-day all-cause mortality and incidence of colorectal cancer.

Among individuals in the older cohort, 515 of 7,627 patients (6.8%) experienced complications after colonoscopy compared with 795 of 30,443 patients (2.6%) in the screening-eligible cohort (P less than .001). Older age was an independent risk factor for postcolonoscopy complications, with individuals older than 75 years having twofold greater odds of complications after colonoscopy (odds ratio, 2.3; 95% confidence interval, 2.0-2.6) compared with individuals aged 50-74 years.

Other independent risk factors for complications included liver disease (OR, 4.7; 95% CI, 3.5-6.5), heart failure (OR, 3.4; 95% CI, 2.5-4.6), smoking history (OR, 3.2; 95% CI, 2.4-4.3), obesity (OR, 2.3; 95% CI, 1.2-4.2), chronic kidney disease (OR, 1.8; 95% CI, 1.1-3.0), cardiac arrhythmia (OR, 1.7; 95% CI, 1.2-2.2), anemia (OR, 1.4; 95% CI, 1.2-1.7), and hypertension (OR, 1.2; 95% CI, 1.0-1.5). Individuals who had previously undergone colonoscopy had a lower risk of complications after the procedure (OR, 0.9; 95% CI, 0.7-1.0).

There was a significantly higher incidence of colorectal cancer treated with surgery in the older group (119 of 7,626; 1.6%) compared with the younger (144 of 30,443; 0.5%) group (P less than .001). Mortality from any cause was also significantly higher in the older group (20 patients; 0.2%) compared with the younger (39 patients; 0.1%) group (P less than .001).

“In accordance with our findings, the decision to perform colonoscopy should be considered carefully in older patients, particularly in the presence of comorbidities,” Dr. Causada-Calo and colleagues wrote.

Aasma Shaukat, MD, MPH, GI section chief at Minneapolis VA Health Care System and professor of medicine at University of Minnesota, said in an interview that screening colonoscopy in a population older than 75 years should be an individualized discussion with a patient who has minimal comorbidities, and the decision to move forward with a colonoscopy should be considered only if a patient’s life expectancy is at least 10 years.

“This study shows that diagnostic colonoscopy is associated with high risk of complications and quantifies the risk, to frame the discussion with the patient about going forward,” she said. “Colorectal cancers are slow growing. In individuals age 75 and older, competing health risks and risk of the colonoscopy often outweigh the small benefit they may derive. Older individuals should thus focus on other health priorities.”

Physicians should make their older patients aware that there is a risk for serious adverse events, including death, which increases after age 75. “[The] risk-benefit ratio for performing colonoscopy needs to carefully weighed,” Dr. Shaukat said. “[T]he patient should be presented with options, including the option of no screening.”

The American Cancer Society advocates “for individualized decision-making regarding screening for individuals after 75 but [does] not give any firm recommendations,” while the U.S. Preventive Services Task Force noted in its recommendations on colorectal cancer screening that the “harms are large and benefits are small” after 75 years of age, and choice to screen for colorectal cancer in that age group is an individual one, Dr. Shaukat said.

Robert A. Smith, PhD, senior vice president of cancer screening at the American Cancer Society, said in an interview that while colonoscopy is the dominant screening test for colorectal cancer, it is not known how often physicians and their older patients discuss noninvasive colorectal cancer screening methods. Noninvasive screening methods such as a high-sensitivity stool test should be a consideration even for older adults with mild chronic conditions, “especially if they have a history of screening with negative results,” he said. “[A] history of regular screening with normal test results should be a basis for considering cessation of screening after age 75, or at least transition to a test with lower risks of complications.”

Future research in this area could use a hybrid model of screening, such as using different tests among various age groups or risk groups, to see whether an invasive or noninvasive method would lower a complication rate, Dr. Smith said. “Further, we need to have a greater understanding of when individuals can confidently stop getting screened, based on their underlying risk and history of prior screening results,” he noted.

Dr. Shaukat said future studies should focus on randomized trials for individuals 75 years and older to assess the benefits and harms of screening, “[d]eveloping risk stratification tools that factor in an individual’s risk of colon cancer, their life expectancy, and guide individualized decision making to undergo screening.”

Dr. Armstrong is the chair of the National Colon Cancer Screening Network for the Canadian Partnership Against Cancer and the past president of the Canadian Association of Gastroenterology. Dr. Albashir has received honoraria and speaker fees from Janssen, and grants from AbbVie and ATGen. Dr. Shaukat and Dr. Smith report no relevant conflicts of interest.

SOURCE: Causada-Calo N et al. JAMA Netw Open. 2020;3(6):e208958.

Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.

Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.

COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.

Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.

The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.

In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.

Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”

As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.

During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”

After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.

Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.

SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.

Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.

Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.

COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.

Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.

The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.

In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.

Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”

As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.

During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”

After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.

Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.

SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.

Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.

Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.

COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.

Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.

The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.

In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.

Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”

As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.

During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”

After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.

Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.

SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.

A World Health Organization (WHO) official is walking back her comments characterizing the spread of SARS-CoV-2 by asymptomatic individuals as “rare.”

Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, caused a stir June 8 when she said that countries are reporting that many of their asymptomatic cases develop into cases of mild disease. For patients with truly asymptomatic disease, countries are “not finding secondary transmission onward. It’s very rare,” she said.

Suppressing symptomatic cases, on the other hand, would result in a “drastic reduction” in transmission, she noted. “But from the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” she said.

But on June 9 – following a day of confusion and criticism – Dr. Van Kerkhove sought to clarify her comments on asymptomatic transmission during a live social media Q&A. She noted that while “the majority of transmission that we know about” is through individuals with symptoms, “there are a subset of people who don’t develop symptoms, and to truly understand how many people don’t have symptoms – we don’t actually have that answer yet.”

Between 6% and 41% of individuals may be asymptomatic based on estimates, she acknowledged.“What we need to better understand is how many of the people in the population don’t have symptoms, and separately, how many of those individuals go on to transmit to others,” she said.

Dr. Van Kerkhove also emphasized that her initial comments were made in response to a question raised at the press conference, and called it a misunderstanding. “I wasn’t stating a policy of WHO or anything like that,” she said. “I was just trying to articulate what we know.”

The phrase “very rare” referred to a subset of studies and reports WHO had received from its member states following asymptomatic individuals with COVID-19. “I was referring to some detailed investigations, cluster investigations, case contact tracing, where we had reports from member states saying that, when we follow asymptomatic cases, it’s very rare – and I used the phrase very rare – that we found a secondary transmission,” she said.

Dr. Van Kerkhove’s initial comments drew criticism from medical and public health professionals, who said the statement was “confusing” and communicated poorly.

Eric J. Topol, MD, tweeted that WHO had “engendered considerable confusion” with the comments about asymptomatic individuals rarely transmitting SARS-CoV-2. Dr. Topol, the author of a recent analysis published in Annals of Internal Medicine that suggested as many as 40%-45% of COVID-19 cases may be asymptomatic, said that it was not possible to determine whether asymptomatic individuals in the cohorts he studied were capable of spread like pre-symptomatic individuals. “We only know the viral loads are similar from multiple reports. And we do know some spread occurs from [asymptomatic] people,” he said.

Andy Slavitt, former acting administrator of the Centers for Medicare and Medicaid Services, said in a tweet that he believed WHO made “an irresponsible statement even though it was based on legitimate observations.” Reports by Member States do not reach a “bar of rigor,” he said.

Natalie E. Dean, PhD, assistant professor of biostatistics at the University of Florida, tweeted that the initial comments by the WHO seemed to be trying to draw a distinction between asymptomatic individuals who never develop symptoms, and presymptomatic individuals who present as asymptomatic, but later develop symptoms. Finding that asymptomatic cases rarely transmit the virus could change how people exposed to those asymptomatic individuals are monitored, but “it seems more of scientific than practical interest,” she noted. “People without current symptoms could be infectious. Act accordingly.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, also weighed in on the controversial WHO comments, telling Good Morning America on June 10 that Dr. Van Kerkhove's initial statement that asymptomatic SARS-CoV-2 transmission is a rare event is "not correct." 

This article was updated 6/10/20.

A World Health Organization (WHO) official is walking back her comments characterizing the spread of SARS-CoV-2 by asymptomatic individuals as “rare.”

Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, caused a stir June 8 when she said that countries are reporting that many of their asymptomatic cases develop into cases of mild disease. For patients with truly asymptomatic disease, countries are “not finding secondary transmission onward. It’s very rare,” she said.

Suppressing symptomatic cases, on the other hand, would result in a “drastic reduction” in transmission, she noted. “But from the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” she said.

But on June 9 – following a day of confusion and criticism – Dr. Van Kerkhove sought to clarify her comments on asymptomatic transmission during a live social media Q&A. She noted that while “the majority of transmission that we know about” is through individuals with symptoms, “there are a subset of people who don’t develop symptoms, and to truly understand how many people don’t have symptoms – we don’t actually have that answer yet.”

Between 6% and 41% of individuals may be asymptomatic based on estimates, she acknowledged.“What we need to better understand is how many of the people in the population don’t have symptoms, and separately, how many of those individuals go on to transmit to others,” she said.

Dr. Van Kerkhove also emphasized that her initial comments were made in response to a question raised at the press conference, and called it a misunderstanding. “I wasn’t stating a policy of WHO or anything like that,” she said. “I was just trying to articulate what we know.”

The phrase “very rare” referred to a subset of studies and reports WHO had received from its member states following asymptomatic individuals with COVID-19. “I was referring to some detailed investigations, cluster investigations, case contact tracing, where we had reports from member states saying that, when we follow asymptomatic cases, it’s very rare – and I used the phrase very rare – that we found a secondary transmission,” she said.

Dr. Van Kerkhove’s initial comments drew criticism from medical and public health professionals, who said the statement was “confusing” and communicated poorly.

Eric J. Topol, MD, tweeted that WHO had “engendered considerable confusion” with the comments about asymptomatic individuals rarely transmitting SARS-CoV-2. Dr. Topol, the author of a recent analysis published in Annals of Internal Medicine that suggested as many as 40%-45% of COVID-19 cases may be asymptomatic, said that it was not possible to determine whether asymptomatic individuals in the cohorts he studied were capable of spread like pre-symptomatic individuals. “We only know the viral loads are similar from multiple reports. And we do know some spread occurs from [asymptomatic] people,” he said.

Andy Slavitt, former acting administrator of the Centers for Medicare and Medicaid Services, said in a tweet that he believed WHO made “an irresponsible statement even though it was based on legitimate observations.” Reports by Member States do not reach a “bar of rigor,” he said.

Natalie E. Dean, PhD, assistant professor of biostatistics at the University of Florida, tweeted that the initial comments by the WHO seemed to be trying to draw a distinction between asymptomatic individuals who never develop symptoms, and presymptomatic individuals who present as asymptomatic, but later develop symptoms. Finding that asymptomatic cases rarely transmit the virus could change how people exposed to those asymptomatic individuals are monitored, but “it seems more of scientific than practical interest,” she noted. “People without current symptoms could be infectious. Act accordingly.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, also weighed in on the controversial WHO comments, telling Good Morning America on June 10 that Dr. Van Kerkhove's initial statement that asymptomatic SARS-CoV-2 transmission is a rare event is "not correct." 

This article was updated 6/10/20.

A World Health Organization (WHO) official is walking back her comments characterizing the spread of SARS-CoV-2 by asymptomatic individuals as “rare.”

Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, caused a stir June 8 when she said that countries are reporting that many of their asymptomatic cases develop into cases of mild disease. For patients with truly asymptomatic disease, countries are “not finding secondary transmission onward. It’s very rare,” she said.

Suppressing symptomatic cases, on the other hand, would result in a “drastic reduction” in transmission, she noted. “But from the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” she said.

But on June 9 – following a day of confusion and criticism – Dr. Van Kerkhove sought to clarify her comments on asymptomatic transmission during a live social media Q&A. She noted that while “the majority of transmission that we know about” is through individuals with symptoms, “there are a subset of people who don’t develop symptoms, and to truly understand how many people don’t have symptoms – we don’t actually have that answer yet.”

Between 6% and 41% of individuals may be asymptomatic based on estimates, she acknowledged.“What we need to better understand is how many of the people in the population don’t have symptoms, and separately, how many of those individuals go on to transmit to others,” she said.

Dr. Van Kerkhove also emphasized that her initial comments were made in response to a question raised at the press conference, and called it a misunderstanding. “I wasn’t stating a policy of WHO or anything like that,” she said. “I was just trying to articulate what we know.”

The phrase “very rare” referred to a subset of studies and reports WHO had received from its member states following asymptomatic individuals with COVID-19. “I was referring to some detailed investigations, cluster investigations, case contact tracing, where we had reports from member states saying that, when we follow asymptomatic cases, it’s very rare – and I used the phrase very rare – that we found a secondary transmission,” she said.

Dr. Van Kerkhove’s initial comments drew criticism from medical and public health professionals, who said the statement was “confusing” and communicated poorly.

Eric J. Topol, MD, tweeted that WHO had “engendered considerable confusion” with the comments about asymptomatic individuals rarely transmitting SARS-CoV-2. Dr. Topol, the author of a recent analysis published in Annals of Internal Medicine that suggested as many as 40%-45% of COVID-19 cases may be asymptomatic, said that it was not possible to determine whether asymptomatic individuals in the cohorts he studied were capable of spread like pre-symptomatic individuals. “We only know the viral loads are similar from multiple reports. And we do know some spread occurs from [asymptomatic] people,” he said.

Andy Slavitt, former acting administrator of the Centers for Medicare and Medicaid Services, said in a tweet that he believed WHO made “an irresponsible statement even though it was based on legitimate observations.” Reports by Member States do not reach a “bar of rigor,” he said.

Natalie E. Dean, PhD, assistant professor of biostatistics at the University of Florida, tweeted that the initial comments by the WHO seemed to be trying to draw a distinction between asymptomatic individuals who never develop symptoms, and presymptomatic individuals who present as asymptomatic, but later develop symptoms. Finding that asymptomatic cases rarely transmit the virus could change how people exposed to those asymptomatic individuals are monitored, but “it seems more of scientific than practical interest,” she noted. “People without current symptoms could be infectious. Act accordingly.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, also weighed in on the controversial WHO comments, telling Good Morning America on June 10 that Dr. Van Kerkhove's initial statement that asymptomatic SARS-CoV-2 transmission is a rare event is "not correct." 

This article was updated 6/10/20.

An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.

“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.

This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”

"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.

Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”

She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.” 

In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”

In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..

When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).

A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.

SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.

This article was updated 6/8/20.

An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.

“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.

This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”

"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.

Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”

She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.” 

In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”

In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..

When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).

A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.

SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.

This article was updated 6/8/20.

An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.

“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.

This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”

"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.

Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”

She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.” 

In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”

In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..

When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).

A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.

SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.

This article was updated 6/8/20.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.