The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.

The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.

STS/ACC TCT registry data queried

Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.

At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.

These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.

These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”

“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.

The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.

But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.

Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
 

More than 90% in NYHA class III or IV heart failure

In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.

When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.

However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).

The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.

It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.

While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
 

Data confirm MR repair is safe during shock

“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.

As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.

“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.

Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.

Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.

Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.

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

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

PARIS – If results of phase 3, randomized clinical trials are the gold standard for cancer drug approvals, then single-arm trials are at best a bronze or even brass standard, with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.

In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.

“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.

“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.

In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
 

Why do single-arm trials?

The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:

• A RCT is not possible because the disease is rare or randomization would be unethical.
• The safety of the drug is established and its potential benefits outweigh its risks.
• The drug is associated with a high and durable overall or objective response rate.
• The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.

Survival endpoints won’t do

Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.

He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.

It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.

“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.

In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
 

On second thought ...

Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.

Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
 

What’s rare and safe?

The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.

He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
 

Cherry-picking patients

Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.

“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.

“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.

Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.

Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.

PARIS – If results of phase 3, randomized clinical trials are the gold standard for cancer drug approvals, then single-arm trials are at best a bronze or even brass standard, with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.

In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.

“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.

“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.

In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
 

Why do single-arm trials?

The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:

• A RCT is not possible because the disease is rare or randomization would be unethical.
• The safety of the drug is established and its potential benefits outweigh its risks.
• The drug is associated with a high and durable overall or objective response rate.
• The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.

Survival endpoints won’t do

Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.

He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.

It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.

“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.

In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
 

On second thought ...

Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.

Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
 

What’s rare and safe?

The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.

He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
 

Cherry-picking patients

Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.

“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.

“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.

Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.

Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.

PARIS – If results of phase 3, randomized clinical trials are the gold standard for cancer drug approvals, then single-arm trials are at best a bronze or even brass standard, with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.

In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.

“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.

“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.

In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
 

Why do single-arm trials?

The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:

• A RCT is not possible because the disease is rare or randomization would be unethical.
• The safety of the drug is established and its potential benefits outweigh its risks.
• The drug is associated with a high and durable overall or objective response rate.
• The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.

Survival endpoints won’t do

Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.

He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.

It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.

“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.

In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
 

On second thought ...

Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.

Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
 

What’s rare and safe?

The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.

He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
 

Cherry-picking patients

Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.

“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.

“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.

Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.

Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

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

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

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

Individuals with esophageal dysmotility had significantly higher scores on measures of airway reflux symptoms, based on data from 441 patients.

Many patients with chronic respiratory diseases experience persistent symptoms despite optimal treatment, and the reason is often unclear and frustrating for clinicians and patients, Dominic L. Sykes, MD, of Hull (England) University Teaching Hospitals NHS Trust, and colleagues wrote.

Although more studies in recent years have explored the association between gastroesophageal reflux and respiratory diseases such as asthma and chronic obstructive pulmonary disease, data on a potential link between esophageal motility and respiratory disease in adults are limited, they noted.

In a study published in Respiratory Medicine, the researchers reviewed data from 441 adults with refractory respiratory symptoms who were treated at a single center between Jan. 1, 2011, and Dec. 1, 2021. Symptoms included persistent cough and breathlessness despite optimal medication. The participants underwent examination with high-resolution esophageal manometry (HROM). Airway reflux was measured using the Hull Airways Reflux Questionnaire (HARQ). The mean age of the patients was 56.5 years, and 64% were women.

Overall, the most common diagnoses were chronic cough (77%), asthma (10%), and interstitial lung disease (7%). The prevalence of esophageal dysmotility was 66%. Patients with esophageal dysmotility had significantly higher HARQ scores than those with normal motility (40.6 vs. 35.3; P < .001). Approximately one-third of the patients had normal motility (34.5%) on HROM, 54% had ineffective esophageal motility, 7.3% had absent contractility, 3.2% had esophageal-gastric junction outflow obstruction, 0.5% had distal esophageal spasm, 0.5% has achalasia, and one patient had hypercontractile esophagus.

No significant differences in manometric diagnoses appeared between men and women. In addition, HARQ scores showed a significant inverse correlation with esophageal contractility as measured by distal contractile integral (DCI).

“The proportion of patients with esophageal dysmotility is consistently high over a range of respiratory diseases, including interstitial lung disease (72%), airways disease (57%), and chronic cough (68%),” and the findings suggest that esophageal disease may play a role in patients with persistent respiratory symptoms, they noted.

The study authors proposed that “impaired peristaltic activity of the esophagus, leading to aspiration of gaseous nonacidic refluxate into the airways, may be a contributor in the development and progression of respiratory disease.” They added that the HARQ offers clinicians a useful screening tool for assessing the need for esophageal study in patients with persistent respiratory symptoms that should be used before considering antireflux surgery.

The study findings were limited by several factors including the lack of lung function data for patients with airway disease and ILD and the inability to show causality between esophageal dysmotility and refractory respiratory symptoms, the researchers noted. Other limitations include the retrospective design, and the lack of data on symptom severity and the subsequent impact on outcomes.

However, the results support the need for additional research into the relationship between esophageal dysmotility, lung function, and symptom burden in chronic respiratory disease, and may inform investigations of therapeutic targets, they concluded.

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

There’s big buzz about the hot prospects for blood tests designed to detect multiple kinds of cancer. President Biden highlighted them in a speech about the Cancer Moonshot program on Sept. 12, just a day after study results touted an experimental test’s ability to detect dozens of kinds of cancer. Meanwhile, the federal government is heralding an upcoming trial that will eventually enroll as many as 225,000 subjects.

There are plenty of reasons to be cautious, however. While the future looks promising, experts say that much more research is needed into multicancer early-detection assays. And if these tests become standard, the oncology field will need to figure out how to navigate a thicket of new challenges.

“Our friends in internal medicine and primary care will be looking to us for guidance. We need to make sure that we’re coming at this without too much optimism before we really have the data,” said Jyoti D. Patel, MD, medical director of thoracic oncology and assistant director for clinical research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.

Dr. Patel is a member of the communications workgroup of the Multicancer Early Detection Consortium, a nonprofit, public-private organization that’s providing insight and guidance into the development of screening tests. The consortium published a position paper earlier this year.

According to Dr. Patel, early cancer screening today can detect only five types of cancer: prostate, breast, lung, cervical, and colon. The Cancer Moonshot program has prioritized research into greatly expanding this number. President Biden referred to this goal in his Sept. 12 speech: “Imagine a simple blood test during an annual physical that could detect cancer early, where the chances of a cure are best.”

Biden said the National Cancer Institute is launching a major trial as part of the Cancer Moonshot program. The Vanguard Study on Multi-Cancer Detection plans to enlist 25,000 healthy women and men between 45 and 70 years old in 2024, then later enroll as many as 225,000 people.

Meanwhile, researchers reported on Sept. 11 that the Galleri multicancer detection blood test found positive cancer signals in 1.4% of 6,621 healthy subjects, and cancer was ultimately confirmed in 38% of those in that group. Nineteen solid tumors and 17 hematologic cancers were diagnosed; 26 of these were cancer types that don’t have routine screening available.

The Galleri test is widely available in the United States, although the $950 cost is not covered by insurance.

While the data is exciting, the high false-positive rate is worrisome, Dr. Patel said. “Are there ways that we can further define that by cancer-risk assessment or by having better captures in our technology that reflect RNA methylation or epigenetic changes that may lead to susceptibility to cancers?”
 

Additional research is essential

Ernest Hawk, MD, vice president and division head of cancer prevention and population sciences at the University of Texas MD Anderson Cancer Center, Houston, said it’s “absolutely essential” that research into screening tests clearly demonstrates improved patient outcomes over time.

“We need to have much longer follow-up of all participants – whether the screening results are positive or negative – and mitigate the potential risks of such testing,” said Dr. Hawk, who’s worked with the Multicancer Early Detection Consortium.

On another front, Northwestern University’s Dr. Patel highlighted that while easy-to-access cancer screening could create tremendous opportunities to treat early cancer and shrink disparities in care, it may produce “an onslaught of patients with early-stage disease. Do we have the workforce to help us?” Also, she said, “if we find a patient with early-stage disease, how are we going to risk-stratify their follow-up and adjuvant therapy? Are there ways to prognosticate with more granularity than we do now?”

What’s next? “Multicancer early-detection tests could truly revolutionize cancer care if they work as we hope they will, but only time, extensive participation in research, and hard work will prove whether that is true or not,” said MD Anderson’s Dr. Hawk. “I anticipate that we’ll have reasonable answers within the next decade, given the pace of existing company-sponsored research and NCI’s planned involvement in testing various technologies available.”

For her part, Dr. Patel said oncologists should be aware that multicancer screening tests are available and be ready to address questions about them. “Think about how you can advise patients in the absence of data,” she said.

Dr. Patel and Dr. Hawk have no relevant disclosures.

There’s big buzz about the hot prospects for blood tests designed to detect multiple kinds of cancer. President Biden highlighted them in a speech about the Cancer Moonshot program on Sept. 12, just a day after study results touted an experimental test’s ability to detect dozens of kinds of cancer. Meanwhile, the federal government is heralding an upcoming trial that will eventually enroll as many as 225,000 subjects.

There are plenty of reasons to be cautious, however. While the future looks promising, experts say that much more research is needed into multicancer early-detection assays. And if these tests become standard, the oncology field will need to figure out how to navigate a thicket of new challenges.

“Our friends in internal medicine and primary care will be looking to us for guidance. We need to make sure that we’re coming at this without too much optimism before we really have the data,” said Jyoti D. Patel, MD, medical director of thoracic oncology and assistant director for clinical research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.

Dr. Patel is a member of the communications workgroup of the Multicancer Early Detection Consortium, a nonprofit, public-private organization that’s providing insight and guidance into the development of screening tests. The consortium published a position paper earlier this year.

According to Dr. Patel, early cancer screening today can detect only five types of cancer: prostate, breast, lung, cervical, and colon. The Cancer Moonshot program has prioritized research into greatly expanding this number. President Biden referred to this goal in his Sept. 12 speech: “Imagine a simple blood test during an annual physical that could detect cancer early, where the chances of a cure are best.”

Biden said the National Cancer Institute is launching a major trial as part of the Cancer Moonshot program. The Vanguard Study on Multi-Cancer Detection plans to enlist 25,000 healthy women and men between 45 and 70 years old in 2024, then later enroll as many as 225,000 people.

Meanwhile, researchers reported on Sept. 11 that the Galleri multicancer detection blood test found positive cancer signals in 1.4% of 6,621 healthy subjects, and cancer was ultimately confirmed in 38% of those in that group. Nineteen solid tumors and 17 hematologic cancers were diagnosed; 26 of these were cancer types that don’t have routine screening available.

The Galleri test is widely available in the United States, although the $950 cost is not covered by insurance.

While the data is exciting, the high false-positive rate is worrisome, Dr. Patel said. “Are there ways that we can further define that by cancer-risk assessment or by having better captures in our technology that reflect RNA methylation or epigenetic changes that may lead to susceptibility to cancers?”
 

Additional research is essential

Ernest Hawk, MD, vice president and division head of cancer prevention and population sciences at the University of Texas MD Anderson Cancer Center, Houston, said it’s “absolutely essential” that research into screening tests clearly demonstrates improved patient outcomes over time.

“We need to have much longer follow-up of all participants – whether the screening results are positive or negative – and mitigate the potential risks of such testing,” said Dr. Hawk, who’s worked with the Multicancer Early Detection Consortium.

On another front, Northwestern University’s Dr. Patel highlighted that while easy-to-access cancer screening could create tremendous opportunities to treat early cancer and shrink disparities in care, it may produce “an onslaught of patients with early-stage disease. Do we have the workforce to help us?” Also, she said, “if we find a patient with early-stage disease, how are we going to risk-stratify their follow-up and adjuvant therapy? Are there ways to prognosticate with more granularity than we do now?”

What’s next? “Multicancer early-detection tests could truly revolutionize cancer care if they work as we hope they will, but only time, extensive participation in research, and hard work will prove whether that is true or not,” said MD Anderson’s Dr. Hawk. “I anticipate that we’ll have reasonable answers within the next decade, given the pace of existing company-sponsored research and NCI’s planned involvement in testing various technologies available.”

For her part, Dr. Patel said oncologists should be aware that multicancer screening tests are available and be ready to address questions about them. “Think about how you can advise patients in the absence of data,” she said.

Dr. Patel and Dr. Hawk have no relevant disclosures.

There’s big buzz about the hot prospects for blood tests designed to detect multiple kinds of cancer. President Biden highlighted them in a speech about the Cancer Moonshot program on Sept. 12, just a day after study results touted an experimental test’s ability to detect dozens of kinds of cancer. Meanwhile, the federal government is heralding an upcoming trial that will eventually enroll as many as 225,000 subjects.

There are plenty of reasons to be cautious, however. While the future looks promising, experts say that much more research is needed into multicancer early-detection assays. And if these tests become standard, the oncology field will need to figure out how to navigate a thicket of new challenges.

“Our friends in internal medicine and primary care will be looking to us for guidance. We need to make sure that we’re coming at this without too much optimism before we really have the data,” said Jyoti D. Patel, MD, medical director of thoracic oncology and assistant director for clinical research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.

Dr. Patel is a member of the communications workgroup of the Multicancer Early Detection Consortium, a nonprofit, public-private organization that’s providing insight and guidance into the development of screening tests. The consortium published a position paper earlier this year.

According to Dr. Patel, early cancer screening today can detect only five types of cancer: prostate, breast, lung, cervical, and colon. The Cancer Moonshot program has prioritized research into greatly expanding this number. President Biden referred to this goal in his Sept. 12 speech: “Imagine a simple blood test during an annual physical that could detect cancer early, where the chances of a cure are best.”

Biden said the National Cancer Institute is launching a major trial as part of the Cancer Moonshot program. The Vanguard Study on Multi-Cancer Detection plans to enlist 25,000 healthy women and men between 45 and 70 years old in 2024, then later enroll as many as 225,000 people.

Meanwhile, researchers reported on Sept. 11 that the Galleri multicancer detection blood test found positive cancer signals in 1.4% of 6,621 healthy subjects, and cancer was ultimately confirmed in 38% of those in that group. Nineteen solid tumors and 17 hematologic cancers were diagnosed; 26 of these were cancer types that don’t have routine screening available.

The Galleri test is widely available in the United States, although the $950 cost is not covered by insurance.

While the data is exciting, the high false-positive rate is worrisome, Dr. Patel said. “Are there ways that we can further define that by cancer-risk assessment or by having better captures in our technology that reflect RNA methylation or epigenetic changes that may lead to susceptibility to cancers?”
 

Additional research is essential

Ernest Hawk, MD, vice president and division head of cancer prevention and population sciences at the University of Texas MD Anderson Cancer Center, Houston, said it’s “absolutely essential” that research into screening tests clearly demonstrates improved patient outcomes over time.

“We need to have much longer follow-up of all participants – whether the screening results are positive or negative – and mitigate the potential risks of such testing,” said Dr. Hawk, who’s worked with the Multicancer Early Detection Consortium.

On another front, Northwestern University’s Dr. Patel highlighted that while easy-to-access cancer screening could create tremendous opportunities to treat early cancer and shrink disparities in care, it may produce “an onslaught of patients with early-stage disease. Do we have the workforce to help us?” Also, she said, “if we find a patient with early-stage disease, how are we going to risk-stratify their follow-up and adjuvant therapy? Are there ways to prognosticate with more granularity than we do now?”

What’s next? “Multicancer early-detection tests could truly revolutionize cancer care if they work as we hope they will, but only time, extensive participation in research, and hard work will prove whether that is true or not,” said MD Anderson’s Dr. Hawk. “I anticipate that we’ll have reasonable answers within the next decade, given the pace of existing company-sponsored research and NCI’s planned involvement in testing various technologies available.”

For her part, Dr. Patel said oncologists should be aware that multicancer screening tests are available and be ready to address questions about them. “Think about how you can advise patients in the absence of data,” she said.

Dr. Patel and Dr. Hawk have no relevant disclosures.

The design improvements introduced in the fourth-generation device for transcatheter mitral valve repair, called the MitraClip G4 (Abbott), appears to yield better outcomes than previous iterations, according to a multinational postapproval study with more than 1,000 patients.

Not least, the 1.3% all-cause mortality at 30 days in this series, called EXPAND G4, “is the lowest that has been reported to date,” reported Ralph Stephan von Bardeleben, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

Ted Bosworth/MDedge News

The evidence of relative advantages was based on comparisons with historical data and a similar study of the previous-generation device. That previous study, called EXPAND, evaluated the MitraClip NTR and ETR systems.

Device times shorter with new device

“There were shorter device times with MitraClip G4,” said Dr. von Bardeleben, referring to a more than 10-minute advantage over the previous generation device (35 minutes in EXPAND G4 vs. 46 min in EXPAND). Although the reduction in overall median procedure time was more modest (77 vs. 80 minutes), Dr. von Bardeleben said these are “the shortest device and procedural times reported to date.”

He also reported what appeared to be incremental advantages across multiple other endpoints, such as procedural success (96.2% vs. 95.8%) and a reduction in the mean clip rate (1.4 vs. 1.5).

Compared with historical outcomes with other devices employed in transcatheter edge-to-edge repair (TEER) of mitral valves, Dr. von Bardeleben contended that the results support the premise that the MitraClip G4 system is a meaningful advance by incorporating such features as an expanded choice of clip sizes, a greater coaptation area, and a more advanced gripper actuation for leaflet grasping.
 

Over 90% achieve MR 1+

Not least, it appears to increase the proportion of patients who achieve a mitral regurgitation grade of 1+ (MR1+) or lower, which is increasingly recognized as the goal of TEER, said Dr. von Bardeleben, head of the Centre of Structure Heart Disease Interventions, Heart Valve Centre, Mainz, Germany.

He said the rates of 91% achieving MR1+ or less and 98% achieved 2+ or lower compare favorably with most other series and exceeds levels achieved with surgery.

Dr. von Bardeleben also contended that, because of its design features, the MitraClip G4 “expands the spectrum of TEER-suitable patients.” He noted that 5% of the patients in this real-world series had a high risk of stenosis owing to such issues as severe annular or leaflet calcification and another 5% had factors that would predict inadequate MR reduction, such as Barlow’s disease, bi-leaflet prolapse, and severe leaflet degeneration.

The 1,164 patients in EXPAND G4 were enrolled from sites in the United States, Europe, Canada, and Japan. For the key outcome measure of procedural success, echocardiograms were assessed by an independent core laboratory. Of the 1,164 patients enrolled, 1,044 (91%) had complete follow-up data at 30 days.

The procedural success rates were reflected in improvements in New York Heart Association (NYHA) functional classes and in the Kansas City Cardiomyopathy Questionnaire (KCCQ), a quality of life instrument. Prior to treatment, 69% were in NYHA class III or greater. Following treatment, the proportion was 17% (P < .0001). The 18-point improvement in the KCCQ was characterized by Dr. von Bardeleben as “both clinically and statistically significant [P < .0001].”

There were no strokes in this series, and the 30-day incidence of myocardial infarction was 0.2%. The proportion requiring cardiovascular surgery within 30 days was less than 1%. The rate of bleeding episodes, all of which were nonserious, was 7%.

The “EXPAND G4 study confirms the safety and effectiveness of the next generation MitraClip G4 system,” according to Dr. von Bardeleben, and it did so “in a contemporary real-world setting.”
 

Outcome data characterized as ‘excellent’

Several invited panelists participating in a discussion following the presentation agreed.

“These results are excellent,” said Raj Makkar, MD, associate director of interventional technologies at Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles. While he was impressed with the fact that only 2% missed the primary endpoint of MR 2+ or lower, he indicated that the 91% achieving MR 1+ or lower might be an even more apt signal that newer-generation devices are improving.

This was echoed by other panelists who appeared to form a general consensus over the premise that the target in TEER should no longer be MR 2+ for most patients.

“We should now be aiming for MR grade of 0-1,” stated panelist Stephan Windecker, MD, chairman, department of cardiology, University of Bern (Switzerland). He indicated that this goal is increasingly reasonable given the advances in device design and greater operator experience.

Dr. von Bardeleben reported financial relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, and Neochord. Dr. Makkar reported financial relationships with Abbott Vascular, Cordis, Edwards Lifesciences, and Medtronic. Dr. Windecker reported financial relationships with more than 30 pharmaceutical companies, including Abbott Vascular, which manufactures MitraClip G4.
 

The design improvements introduced in the fourth-generation device for transcatheter mitral valve repair, called the MitraClip G4 (Abbott), appears to yield better outcomes than previous iterations, according to a multinational postapproval study with more than 1,000 patients.

Not least, the 1.3% all-cause mortality at 30 days in this series, called EXPAND G4, “is the lowest that has been reported to date,” reported Ralph Stephan von Bardeleben, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

Ted Bosworth/MDedge News

The evidence of relative advantages was based on comparisons with historical data and a similar study of the previous-generation device. That previous study, called EXPAND, evaluated the MitraClip NTR and ETR systems.

Device times shorter with new device

“There were shorter device times with MitraClip G4,” said Dr. von Bardeleben, referring to a more than 10-minute advantage over the previous generation device (35 minutes in EXPAND G4 vs. 46 min in EXPAND). Although the reduction in overall median procedure time was more modest (77 vs. 80 minutes), Dr. von Bardeleben said these are “the shortest device and procedural times reported to date.”

He also reported what appeared to be incremental advantages across multiple other endpoints, such as procedural success (96.2% vs. 95.8%) and a reduction in the mean clip rate (1.4 vs. 1.5).

Compared with historical outcomes with other devices employed in transcatheter edge-to-edge repair (TEER) of mitral valves, Dr. von Bardeleben contended that the results support the premise that the MitraClip G4 system is a meaningful advance by incorporating such features as an expanded choice of clip sizes, a greater coaptation area, and a more advanced gripper actuation for leaflet grasping.
 

Over 90% achieve MR 1+

Not least, it appears to increase the proportion of patients who achieve a mitral regurgitation grade of 1+ (MR1+) or lower, which is increasingly recognized as the goal of TEER, said Dr. von Bardeleben, head of the Centre of Structure Heart Disease Interventions, Heart Valve Centre, Mainz, Germany.

He said the rates of 91% achieving MR1+ or less and 98% achieved 2+ or lower compare favorably with most other series and exceeds levels achieved with surgery.

Dr. von Bardeleben also contended that, because of its design features, the MitraClip G4 “expands the spectrum of TEER-suitable patients.” He noted that 5% of the patients in this real-world series had a high risk of stenosis owing to such issues as severe annular or leaflet calcification and another 5% had factors that would predict inadequate MR reduction, such as Barlow’s disease, bi-leaflet prolapse, and severe leaflet degeneration.

The 1,164 patients in EXPAND G4 were enrolled from sites in the United States, Europe, Canada, and Japan. For the key outcome measure of procedural success, echocardiograms were assessed by an independent core laboratory. Of the 1,164 patients enrolled, 1,044 (91%) had complete follow-up data at 30 days.

The procedural success rates were reflected in improvements in New York Heart Association (NYHA) functional classes and in the Kansas City Cardiomyopathy Questionnaire (KCCQ), a quality of life instrument. Prior to treatment, 69% were in NYHA class III or greater. Following treatment, the proportion was 17% (P < .0001). The 18-point improvement in the KCCQ was characterized by Dr. von Bardeleben as “both clinically and statistically significant [P < .0001].”

There were no strokes in this series, and the 30-day incidence of myocardial infarction was 0.2%. The proportion requiring cardiovascular surgery within 30 days was less than 1%. The rate of bleeding episodes, all of which were nonserious, was 7%.

The “EXPAND G4 study confirms the safety and effectiveness of the next generation MitraClip G4 system,” according to Dr. von Bardeleben, and it did so “in a contemporary real-world setting.”
 

Outcome data characterized as ‘excellent’

Several invited panelists participating in a discussion following the presentation agreed.

“These results are excellent,” said Raj Makkar, MD, associate director of interventional technologies at Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles. While he was impressed with the fact that only 2% missed the primary endpoint of MR 2+ or lower, he indicated that the 91% achieving MR 1+ or lower might be an even more apt signal that newer-generation devices are improving.

This was echoed by other panelists who appeared to form a general consensus over the premise that the target in TEER should no longer be MR 2+ for most patients.

“We should now be aiming for MR grade of 0-1,” stated panelist Stephan Windecker, MD, chairman, department of cardiology, University of Bern (Switzerland). He indicated that this goal is increasingly reasonable given the advances in device design and greater operator experience.

Dr. von Bardeleben reported financial relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, and Neochord. Dr. Makkar reported financial relationships with Abbott Vascular, Cordis, Edwards Lifesciences, and Medtronic. Dr. Windecker reported financial relationships with more than 30 pharmaceutical companies, including Abbott Vascular, which manufactures MitraClip G4.
 

The design improvements introduced in the fourth-generation device for transcatheter mitral valve repair, called the MitraClip G4 (Abbott), appears to yield better outcomes than previous iterations, according to a multinational postapproval study with more than 1,000 patients.

Not least, the 1.3% all-cause mortality at 30 days in this series, called EXPAND G4, “is the lowest that has been reported to date,” reported Ralph Stephan von Bardeleben, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

Ted Bosworth/MDedge News

The evidence of relative advantages was based on comparisons with historical data and a similar study of the previous-generation device. That previous study, called EXPAND, evaluated the MitraClip NTR and ETR systems.

Device times shorter with new device

“There were shorter device times with MitraClip G4,” said Dr. von Bardeleben, referring to a more than 10-minute advantage over the previous generation device (35 minutes in EXPAND G4 vs. 46 min in EXPAND). Although the reduction in overall median procedure time was more modest (77 vs. 80 minutes), Dr. von Bardeleben said these are “the shortest device and procedural times reported to date.”

He also reported what appeared to be incremental advantages across multiple other endpoints, such as procedural success (96.2% vs. 95.8%) and a reduction in the mean clip rate (1.4 vs. 1.5).

Compared with historical outcomes with other devices employed in transcatheter edge-to-edge repair (TEER) of mitral valves, Dr. von Bardeleben contended that the results support the premise that the MitraClip G4 system is a meaningful advance by incorporating such features as an expanded choice of clip sizes, a greater coaptation area, and a more advanced gripper actuation for leaflet grasping.
 

Over 90% achieve MR 1+

Not least, it appears to increase the proportion of patients who achieve a mitral regurgitation grade of 1+ (MR1+) or lower, which is increasingly recognized as the goal of TEER, said Dr. von Bardeleben, head of the Centre of Structure Heart Disease Interventions, Heart Valve Centre, Mainz, Germany.

He said the rates of 91% achieving MR1+ or less and 98% achieved 2+ or lower compare favorably with most other series and exceeds levels achieved with surgery.

Dr. von Bardeleben also contended that, because of its design features, the MitraClip G4 “expands the spectrum of TEER-suitable patients.” He noted that 5% of the patients in this real-world series had a high risk of stenosis owing to such issues as severe annular or leaflet calcification and another 5% had factors that would predict inadequate MR reduction, such as Barlow’s disease, bi-leaflet prolapse, and severe leaflet degeneration.

The 1,164 patients in EXPAND G4 were enrolled from sites in the United States, Europe, Canada, and Japan. For the key outcome measure of procedural success, echocardiograms were assessed by an independent core laboratory. Of the 1,164 patients enrolled, 1,044 (91%) had complete follow-up data at 30 days.

The procedural success rates were reflected in improvements in New York Heart Association (NYHA) functional classes and in the Kansas City Cardiomyopathy Questionnaire (KCCQ), a quality of life instrument. Prior to treatment, 69% were in NYHA class III or greater. Following treatment, the proportion was 17% (P < .0001). The 18-point improvement in the KCCQ was characterized by Dr. von Bardeleben as “both clinically and statistically significant [P < .0001].”

There were no strokes in this series, and the 30-day incidence of myocardial infarction was 0.2%. The proportion requiring cardiovascular surgery within 30 days was less than 1%. The rate of bleeding episodes, all of which were nonserious, was 7%.

The “EXPAND G4 study confirms the safety and effectiveness of the next generation MitraClip G4 system,” according to Dr. von Bardeleben, and it did so “in a contemporary real-world setting.”
 

Outcome data characterized as ‘excellent’

Several invited panelists participating in a discussion following the presentation agreed.

“These results are excellent,” said Raj Makkar, MD, associate director of interventional technologies at Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles. While he was impressed with the fact that only 2% missed the primary endpoint of MR 2+ or lower, he indicated that the 91% achieving MR 1+ or lower might be an even more apt signal that newer-generation devices are improving.

This was echoed by other panelists who appeared to form a general consensus over the premise that the target in TEER should no longer be MR 2+ for most patients.

“We should now be aiming for MR grade of 0-1,” stated panelist Stephan Windecker, MD, chairman, department of cardiology, University of Bern (Switzerland). He indicated that this goal is increasingly reasonable given the advances in device design and greater operator experience.

Dr. von Bardeleben reported financial relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, and Neochord. Dr. Makkar reported financial relationships with Abbott Vascular, Cordis, Edwards Lifesciences, and Medtronic. Dr. Windecker reported financial relationships with more than 30 pharmaceutical companies, including Abbott Vascular, which manufactures MitraClip G4.
 

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of this presentation, and the findings from the chest x-ray (as shown), the likely diagnosis is non–small cell lung cancer (NSCLC), Pancoast tumor, also known as superior sulcus tumor. Pancoast tumors are rare, representing about 3%-5% of all lung cancers, and invade the structures in the apex of the chest, including the first thoracic ribs or periosteum, the lower nerve roots of the bronchial plexus, the sympathetic chain and stellate ganglion, or the subclavian vessels. The majority of Pancoast tumors are non–small cell carcinomas.

Because of their pulmonary location, Pancoast tumors are characterized by several distinct symptoms. As seen in this case, patients often present with shoulder pain that worsens over time, especially with invasion of the chest wall and brachial plexus. The pain may radiate to the neck; axilla; anterior chest wall; and medial aspect of the arm, forearm, and wrist. If Pancoast tumors infiltrate the ulnar nerve, patients may present with weakness and muscle atrophy of the intrinsic muscles of the hand. In addition, invasion of the sympathetic chain and of the inferior cervical ganglion can cause Horner syndrome (ptosis, miosis, enophthalmos, and anhidrosis). Lastly, upper-arm edema may develop, signaling invasion and potentially occlusion of the subclavian vein.

During workup, CT-guided core biopsy is the first-line diagnostic test for Pancoast tumors. CT of the chest can confirm the presence of an apical mass and its position in relation to other structures of the thoracic inlet. MRI can further assess suspected brachial plexus, subclavian vessels, spine, and neural foramina invasion, specifying the extent of the disease and of the amount of nerve-root involvement.

For resectable Pancoast tumors, the National Comprehensive Cancer Network recommends chemoradiation, followed by surgical resection and chemotherapy. Preoperative chemoradiation together with surgical resection has shown a 2-year survival between 50% and 70%. Depending on biomarker status (certain EGFR mutations or programmed death ligand 1 levels ≥ 1%), the addition of either atezolizumab or osimertinib is advised. However, the positioning of Pancoast tumors can pose a surgical challenge, and if the lesion remains unresectable after preoperative concurrent chemoradiation, then consolidation immunotherapy with durvalumab is recommended.

Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.

Karl J. D'Silva, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Key clinical point: In patients with hepatocellular carcinoma (HCC), transarterial radioembolization (TARE) provides significantly longer time to progression (TTP) than transarterial chemoembolization (TACE), but does not significantly prolong overall survival.

Major finding: TARE vs TACE significantly prolonged the mean TTP (17.5 vs 9.8 months; 95% CI 1.3-8.3 months) but resulted in comparable overall survival (absolute difference −0.55 months; 95% CI −1.95 to 3.05 months).

Study details: This was a meta-analysis of 17 studies involving 2465 unique patients that directly compared TACE and TARE for treating HCC.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared serving as consultants or advisory board members of or receiving grants from various sources.

Source: Brown AM et al. TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta-analysis. Cancer Med. 2022 (Aug 9). Doi: 10.1002/cam4.5125

Key clinical point: In patients with hepatocellular carcinoma (HCC), transarterial radioembolization (TARE) provides significantly longer time to progression (TTP) than transarterial chemoembolization (TACE), but does not significantly prolong overall survival.

Major finding: TARE vs TACE significantly prolonged the mean TTP (17.5 vs 9.8 months; 95% CI 1.3-8.3 months) but resulted in comparable overall survival (absolute difference −0.55 months; 95% CI −1.95 to 3.05 months).

Study details: This was a meta-analysis of 17 studies involving 2465 unique patients that directly compared TACE and TARE for treating HCC.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared serving as consultants or advisory board members of or receiving grants from various sources.

Source: Brown AM et al. TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta-analysis. Cancer Med. 2022 (Aug 9). Doi: 10.1002/cam4.5125

Key clinical point: In patients with hepatocellular carcinoma (HCC), transarterial radioembolization (TARE) provides significantly longer time to progression (TTP) than transarterial chemoembolization (TACE), but does not significantly prolong overall survival.

Major finding: TARE vs TACE significantly prolonged the mean TTP (17.5 vs 9.8 months; 95% CI 1.3-8.3 months) but resulted in comparable overall survival (absolute difference −0.55 months; 95% CI −1.95 to 3.05 months).

Study details: This was a meta-analysis of 17 studies involving 2465 unique patients that directly compared TACE and TARE for treating HCC.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared serving as consultants or advisory board members of or receiving grants from various sources.

Source: Brown AM et al. TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta-analysis. Cancer Med. 2022 (Aug 9). Doi: 10.1002/cam4.5125

Key clinical point: Baseline des-gamma-carboxy prothrombin (DCP) levels and neutrophil-to-lymphocyte ratio (NLR) may serve as predictive biomarkers of survival in patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (ATE+BEV) therapy.

Major finding: Multivariate analysis revealed that a DCP level of ≥186 mAU/mL and an NLR of ≥2.5 independently predict overall survival (adjusted hazard ratio [aHR] 5.102; P < .001; and aHR 3.584; P  =  .001, respectively) and progression-free survival (aHR 2.311; P  =  .002; and aHR 1.938; P  =  .012, respectively).

Study details: The data come from a real-world observational study that included 121 patients with advanced HCC who received ≥1 cycle of ATE+BEV treatment.

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korea government. Some authors declared receiving honoraria or research grants from various sources.

Source: Chon YE, Cheon J, et al. Predictive biomarkers of survival in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab treatment. Cancer Med. 2022 (Aug 23). Doi: 10.1002/cam4.5161

Key clinical point: Baseline des-gamma-carboxy prothrombin (DCP) levels and neutrophil-to-lymphocyte ratio (NLR) may serve as predictive biomarkers of survival in patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (ATE+BEV) therapy.

Major finding: Multivariate analysis revealed that a DCP level of ≥186 mAU/mL and an NLR of ≥2.5 independently predict overall survival (adjusted hazard ratio [aHR] 5.102; P < .001; and aHR 3.584; P  =  .001, respectively) and progression-free survival (aHR 2.311; P  =  .002; and aHR 1.938; P  =  .012, respectively).

Study details: The data come from a real-world observational study that included 121 patients with advanced HCC who received ≥1 cycle of ATE+BEV treatment.

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korea government. Some authors declared receiving honoraria or research grants from various sources.

Source: Chon YE, Cheon J, et al. Predictive biomarkers of survival in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab treatment. Cancer Med. 2022 (Aug 23). Doi: 10.1002/cam4.5161

Key clinical point: Baseline des-gamma-carboxy prothrombin (DCP) levels and neutrophil-to-lymphocyte ratio (NLR) may serve as predictive biomarkers of survival in patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (ATE+BEV) therapy.

Major finding: Multivariate analysis revealed that a DCP level of ≥186 mAU/mL and an NLR of ≥2.5 independently predict overall survival (adjusted hazard ratio [aHR] 5.102; P < .001; and aHR 3.584; P  =  .001, respectively) and progression-free survival (aHR 2.311; P  =  .002; and aHR 1.938; P  =  .012, respectively).

Study details: The data come from a real-world observational study that included 121 patients with advanced HCC who received ≥1 cycle of ATE+BEV treatment.

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korea government. Some authors declared receiving honoraria or research grants from various sources.

Source: Chon YE, Cheon J, et al. Predictive biomarkers of survival in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab treatment. Cancer Med. 2022 (Aug 23). Doi: 10.1002/cam4.5161