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Finerenone + SGLT2 inhibitor of benefit in diabetes with CKD?
New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.
The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.
Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.
Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.
Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.
For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.
‘A lot of interest in finerenone’ in U.S.
“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.
The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.
But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.
The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.
He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.
The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”
Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.
“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.
Finerenone has also been recently approved in the European Union.
‘Consistent’ benefits irrespective of SGLT2 inhibitors
“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.
That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.
“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.
The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
‘Impressive’ effect on cardiovascular events
The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.
The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.
“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.
He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”
Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.
“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.
He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.
The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m2, are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.
“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m2, but this was less than 1% of the enrolled population,” Dr. Desai observed.
FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.
The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.
Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.
Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.
Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.
For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.
‘A lot of interest in finerenone’ in U.S.
“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.
The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.
But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.
The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.
He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.
The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”
Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.
“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.
Finerenone has also been recently approved in the European Union.
‘Consistent’ benefits irrespective of SGLT2 inhibitors
“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.
That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.
“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.
The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
‘Impressive’ effect on cardiovascular events
The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.
The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.
“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.
He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”
Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.
“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.
He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.
The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m2, are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.
“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m2, but this was less than 1% of the enrolled population,” Dr. Desai observed.
FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.
The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.
Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.
Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.
Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.
For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.
‘A lot of interest in finerenone’ in U.S.
“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.
The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.
But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.
The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.
He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.
The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”
Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.
“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.
Finerenone has also been recently approved in the European Union.
‘Consistent’ benefits irrespective of SGLT2 inhibitors
“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.
That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.
“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.
The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
‘Impressive’ effect on cardiovascular events
The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.
The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.
“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.
He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”
Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.
“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.
He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.
The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m2, are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.
“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m2, but this was less than 1% of the enrolled population,” Dr. Desai observed.
FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE WORLD CONGRESS OF NEPHROLOGY
Dupilumab shows histological and clinical benefit in larger eosinophilic esophagitis cohort
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.
EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.
Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.
Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)
Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.
Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group.
Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.
On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).
“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.
Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.
In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”
LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.
A version of this article first appeared on Medscape.com.
REPORTING FROM AAAAI
Ozanimod shows long-term safety, despite a pandemic
The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.
Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.
The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.
“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.
Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.
“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
Stable efficacy and no worsening of COVID-19 outcomes
Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.
The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.
Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.
Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.
Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).
Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
Encouraging data
The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.
She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.
The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.
Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.
The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.
“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.
Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.
“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
Stable efficacy and no worsening of COVID-19 outcomes
Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.
The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.
Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.
Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.
Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).
Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
Encouraging data
The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.
She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.
The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.
Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.
The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.
“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.
Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.
“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
Stable efficacy and no worsening of COVID-19 outcomes
Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.
The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.
Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.
Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.
Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).
Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
Encouraging data
The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.
She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.
The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
FROM ACTRIMS FORUM 2022
Asthma: Easy strategy reduces exacerbations, improves control
PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.
The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.
Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.
Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.
Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.
Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”
Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.
This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.
The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:
- better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
- improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
- fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).
Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”
The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.
The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.
The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.
Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.
Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.
Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.
Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”
Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.
This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.
The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:
- better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
- improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
- fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).
Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”
The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.
The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.
The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.
Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.
Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.
Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.
Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”
Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.
This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.
The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:
- better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
- improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
- fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).
Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”
The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.
The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Robust’ increase in tics during the pandemic explained?
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Can liquid biopsy predict oropharyngeal cancer recurrence?
PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.
Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.
And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.
“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.
Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.
Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.
Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.
The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.
Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.
Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.
Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.
According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.
“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.
The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.
A version of this article first appeared on Medscape.com.
PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.
Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.
And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.
“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.
Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.
Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.
Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.
The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.
Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.
Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.
Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.
According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.
“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.
The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.
A version of this article first appeared on Medscape.com.
PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.
Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.
And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.
“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.
Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.
Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.
Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.
The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.
Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.
Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.
Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.
According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.
“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.
The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.
A version of this article first appeared on Medscape.com.
Self-care tips for clinicians as COVID-19 lingers
LAS VEGAS – according to Jon A. Levenson, MD.
“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”
Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.
“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”
How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”
Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”
Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”
Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”
Dr. Levenson reported having no disclosures related to his presentation.
LAS VEGAS – according to Jon A. Levenson, MD.
“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”
Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.
“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”
How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”
Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”
Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”
Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”
Dr. Levenson reported having no disclosures related to his presentation.
LAS VEGAS – according to Jon A. Levenson, MD.
“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”
Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.
“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”
How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”
Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”
Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”
Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”
Dr. Levenson reported having no disclosures related to his presentation.
AT NPA 2022
B-cell therapy for MS may impact COVID-19 vaccination
, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.
“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.
The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.
The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.
After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.
The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).
The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).
Subanalyses by sex and vaccine type revealed no differences in nAb levels.
The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
Some answers, more questions
The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.
He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.
The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.
Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.
“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.
The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.
The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.
After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.
The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).
The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).
Subanalyses by sex and vaccine type revealed no differences in nAb levels.
The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
Some answers, more questions
The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.
He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.
The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.
Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.
“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.
The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.
The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.
After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.
The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).
The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).
Subanalyses by sex and vaccine type revealed no differences in nAb levels.
The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
Some answers, more questions
The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.
He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.
The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.
Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.
FROM ACTRIMS FORUM 2022
Aspirin fails to inhibit breast cancer recurrence
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
FROM ASCO PLENARY SERIES
Bladder cancer need not always require radical cystectomy
The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.
Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.
After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium
“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.
Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.
However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.
The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
A ‘very valuable’ option
Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.
Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”
Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.
The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.
Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.
Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.
At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.
Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).
There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.
The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.
Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.
The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.
There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.
This article was updated on 3/10/22.
The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.
Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.
After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium
“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.
Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.
However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.
The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
A ‘very valuable’ option
Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.
Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”
Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.
The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.
Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.
Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.
At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.
Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).
There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.
The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.
Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.
The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.
There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.
This article was updated on 3/10/22.
The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.
Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.
After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium
“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.
Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.
However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.
The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
A ‘very valuable’ option
Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.
Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”
Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.
The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.
Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.
Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.
At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.
Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).
There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.
The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.
Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.
The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.
There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.
This article was updated on 3/10/22.
FROM ASCO GU 2022