Conference Coverage

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

Adults aged 85 years and older who logged an hour or more of walking each week had a 40% reduced risk of all-cause mortality compared with less active peers, according to data from more than 7,000 individuals.

“Aging is accompanied by reduced physical activity and increased sedentary behavior, and reduced physical activity is associated with decreased life expectancy,” Moo-Nyun Jin, MD, of Inje University Sanggye Paik Hospital, Seoul, South Korea, said in an interview.

Reduced physical activity was especially likely in the elderly during the COVID-19 pandemic, he added.

oneinchpunch/Thinkstock

“Promoting walking may be a simple way to help older adults avoid inactivity and encourage an active lifestyle for all-cause and cardiovascular mortality risk reduction,” Dr. Jin said.

Although walking is generally an easy form of exercise for the older adult population, the specific benefit of walking on reducing mortality has not been well studied, according to Dr. Jin and colleagues.

For adults of any age, current guidelines recommend at least 150 minutes per week of moderate activity or 75 minutes per week of vigorous activity, but the amount of physical activity tends to decline with age, and activity recommendations are more difficult to meet, the authors wrote in a press release accompanying their study.

In the study, to be presented at the European Society of Cardiology Congress on Aug. 28 (Abstract 85643), the researchers reviewed data from 7,047 adults aged 85 years and older who participated in the Korean National Health Screening Program. The average age of the study population was 87 years, and 68% were women. Participants completed questionnaires about the amount of time spent in leisure time activities each week, including walking at a slow pace, moderate activity (such as cycling or brisk walking), and vigorous activity (such as running).

Those who walked at a slow pace for at least 1 hour per week had a 40% reduced risk of all-cause mortality and a 39% reduced risk of cardiovascular mortality, compared with inactive participants.

The proportions of participants who reported walking, moderate activity,­ and vigorous ­intensity physical activity were 42.5%, 14.7%, and 11.0%, respectively. Roughly one-third (33%) of those who reported slow walking each week also reported moderate or vigorous physical activity.

However, walking for 1 hour per week significantly reduced the risk for all-cause mortality and cardiovascular mortality among individuals who reported walking only, without other moderate or vigorous physical activity (hazard ratio, 0.50 and 0.46, respectively).

“Walking was linked with a lower likelihood of dying in older adults, regardless of whether or not they did any moderate to vigorous intensity physical activity,” Dr. Jin told this news organization. “Our study indicates that walking even just 1 hour every week is advantageous to those aged 85 years and older compared to being inactive.”

The hour of walking need not be in long bouts, 10 minutes each day will do, Dr. Jin added.

The participants were divided into five groups based on reported amount of weekly walking. More than half (57.5%) reported no slow walking, 8.5% walked less than 1 hour per week, 12.0% walked 1-2 hours, 8.7% walked 2-3 hours, and 13.3% walked more than 3 hours.

Although the study was limited by the reliance on self-reports, the results were strengthened by the large sample size and support the value of easy walking for adults aged 85 years and older compared to being inactive.

“Walking may present an opportunity for promoting physical activity among the elderly population, offering a simple way to avoid inactivity and increase physical activity,” said Dr. Jin. However, more research is needed to evaluate the association between mortality and walking by objective measurement of walking levels, using a device such as a smart watch, he noted.

 

Results are preliminary

“This is an observational study, not an experiment, so it means causality cannot be presumed,” said Maria Fiatarone Singh, MD, a geriatrician with a focus on exercise physiology at the University of Sydney, in an interview. “In other words, it is possible that diseases resulting in mortality prevented people from walking rather than the other way around,” she noted. The only published experimental study on exercise and mortality in older adults was conducted by Dr. Fiatarone Singh and colleagues in Norway. In that study, published in the British Medical Journal in 2020, high-intensity training programs were associated with reduced all-cause mortality compared with inactive controls and individuals who engaged in moderate intensity exercise.

The current study “would have needed to control for many factors related to mortality, such as cardiovascular disease, hypertension, diabetes, malnutrition, and dementia to see what residual benefit might be related to walking,” Dr. Fiatarone Singh said.

“Although walking seems easy and safe, in fact people who are frail, sarcopenic, osteoporotic, or have fallen are recommended to do resistance and balance training rather than walking, and add walking later when they are able to do it safely,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Fiatarone Singh had no financial conflicts to disclose.

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.

PORTLAND, ORE. – When patients present to Brandon L. Adler, MD, with dermatitis on the eyelid, face, or neck, he routinely asks them if they apply essential oils on their skin, or if they have an essential oil diffuser or nebulizer in their home.

“The answer is frequently ‘yes,’ ” Dr. Adler, clinical assistant professor of dermatology at the University of Southern California, Los Angeles, said at the annual meeting of the Pacific Dermatologic Association. “Essential oils are widely used throughout the wellness industry. They are contained in personal care products, beauty products, natural cleaning products, and they’re being diffused by our patients into the air. More than 75 essential oils are reported to cause allergic contact dermatitis.”

yangna/iStock/Getty Images

Natural chemical components contained in essential oils can cause skin reactions, especially linalool and limonene. “Linalool is most classically associated with lavender, while limonene is associated with citrus, but they’re found in many different plants,” said Dr. Adler, who directs USC’s contact dermatitis clinic. “On their own, linalool and limonene are not particularly allergenic; they’re not a big deal in the patch test clinic. The problem comes when we add air to the mix, because they oxidize to hydroperoxides of linalool and limonene. These are quite potent allergens.”

According to the most recent North American Contact Dermatitis Group data, 8.9% of patients undergoing patch testing tested positive to linalool hydroperoxides and 2.6% were positive to limonene hydroperoxides.

Dr. Adler discussed the case of a female massage therapist who presented with refractory hand dermatitis and was on methotrexate and dupilumab at the time of consultation but was still symptomatic. She patch-tested positive to limonene and linalool hydroperoxides as well as multiple essential oils that she had been using with her clients, ranging from sacred frankincense oil to basil oil, and she was advised to massage using only coconut or vegetable oils.

Essential oil allergy may also be related to cannabis allergy. According to Dr. Adler, allergic contact dermatitis to cannabis has been rarely reported, but in an analysis of 103 commercial topical cannabinoid preparations that he published with Vincent DeLeo, MD, also with USC, 84% contained a NACDG allergen, frequently essential oils.

More recently, Dr. Adler and colleagues reported the case of a 40-year-old woman who was referred for patch testing for nummular dermatitis that wasn’t responding to treatment. The patient was found to be using topical cannabis and also grew cannabis at home. “She asked to be patch-tested to her homegrown cannabis and had a strong positive patch test to the cannabis, linalool and limonene hydroperoxides, and other essential oils,” Dr. Adler recalled. “We sent her cannabis sample for analysis at a commercial lab and found that it contained limonene and other allergenic terpene chemicals.

“We’re just starting to unravel what this means in terms of our patients and how to manage them, but many are using topical cannabis and topical CBD. I suspect this is a lot less rare than we realize.”

Another recent case from Europe reported allergic contact dermatitis to Cannabis sativa (hemp) seed oil following topical application, with positive patch testing.

Dr. Adler disclosed that he has received research grants from the American Contact Dermatitis Society. He is also an investigator for AbbVie and a consultant for the Skin Research Institute.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.

Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.

New therapies sought

In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.

It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
 

Evoking emotions

A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.

Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).

Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.

Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.

Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).

These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.

In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.

Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
 

Ketamine’s effects

Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.

Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.

Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.

Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
 

Ketamine 2.0?

Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.

A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.

In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).

In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.

Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.

According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.

In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
 

Add-on psilocybin?

While ketamine is only suitable for acute intervention, owing to the short duration of effect, the effects of psilocybin can last for weeks or even months following administration, and this has been seen in more than just a few patients. What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.

The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.

The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
 

Two therapeutic settings

Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.

Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.

Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
 

Euphoria and disillusionment

The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.

“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.

“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
 

Outlook for psilocybin

Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.

“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”

In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.

Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.

In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
 

Possible psilocybin improvement?

Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.

In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.

When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.

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

Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.

Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.

New therapies sought

In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.

It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
 

Evoking emotions

A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.

Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).

Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.

Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.

Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).

These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.

In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.

Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
 

Ketamine’s effects

Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.

Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.

Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.

Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
 

Ketamine 2.0?

Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.

A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.

In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).

In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.

Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.

According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.

In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
 

Add-on psilocybin?

While ketamine is only suitable for acute intervention, owing to the short duration of effect, the effects of psilocybin can last for weeks or even months following administration, and this has been seen in more than just a few patients. What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.

The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.

The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
 

Two therapeutic settings

Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.

Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.

Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
 

Euphoria and disillusionment

The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.

“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.

“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
 

Outlook for psilocybin

Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.

“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”

In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.

Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.

In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
 

Possible psilocybin improvement?

Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.

In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.

When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.

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

Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.

Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.

New therapies sought

In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.

It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
 

Evoking emotions

A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.

Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).

Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.

Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.

Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).

These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.

In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.

Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
 

Ketamine’s effects

Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.

Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.

Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.

Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
 

Ketamine 2.0?

Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.

A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.

In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).

In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.

Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.

According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.

In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
 

Add-on psilocybin?

While ketamine is only suitable for acute intervention, owing to the short duration of effect, the effects of psilocybin can last for weeks or even months following administration, and this has been seen in more than just a few patients. What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.

The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.

The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
 

Two therapeutic settings

Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.

Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.

Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
 

Euphoria and disillusionment

The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.

“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.

“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
 

Outlook for psilocybin

Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.

“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”

In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.

Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.

In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
 

Possible psilocybin improvement?

Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.

In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.

When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.

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

PORTLAND, ORE. – If you’re uncomfortable asking new dermatology patients about their sexual orientation and gender identity, they’re likely to sense your unease.

“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.

In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”

On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”

Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”

Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”

Dr. Yeung reported having no relevant disclosures.

PORTLAND, ORE. – If you’re uncomfortable asking new dermatology patients about their sexual orientation and gender identity, they’re likely to sense your unease.

“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.

In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”

On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”

Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”

Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”

Dr. Yeung reported having no relevant disclosures.

PORTLAND, ORE. – If you’re uncomfortable asking new dermatology patients about their sexual orientation and gender identity, they’re likely to sense your unease.

“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.

In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”

On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”

Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”

Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”

Dr. Yeung reported having no relevant disclosures.

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.