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Clinical trial: Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Latest on dupilumab for atopic dermatitis: The who and how
GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.
CHRONOS was a 14-country, 1-year, randomized, double-blind, placebo-controlled, phase 3 clinical trial in which 740 adults with moderate to very severe AD were assigned to mid-potency topical corticosteroids along with topical calcineurin inhibitors as needed in steroid-sensitive locations, then randomized 3:1:3 to either subcutaneous dupilumab (Dupixent) at 300 mg once weekly, placebo injections, or dupilumab at 300 mg every 2 weeks on top of the topical therapy.
Dupilumab, a fully human monoclonal antibody, was approved by the Food and Drug Administration in March 2017 at a loading dose of 600 mg, followed by 300 mg every 2 weeks for treatment of adults with moderate to severe AD. The biologic agent is soon expected to be approved across the European Union as well. CHRONOS was the first major trial designed to replicate how the biologic would likely be utilized in real-world clinical practice: that is, in conjunction with rather than as an alternative to topical therapy. Earlier pivotal phase 3 trials were required by regulatory agencies to pit dupilumab monotherapy against placebo.
CHRONOS participants were “a very tough crowd, so to speak,” the dermatologist recalled. Their median body surface area of involvement was a whopping 55%, 60% were men, the median baseline EASI (Eczema Area and Severity Index) score was 30, and fully half of patients had an IGA (Investigator’s Global Assessment) score of 4, indicative of severe disease. Plus, comorbid atopic/allergic diseases were common: half of subjects had a history of asthma, nearly half had a history of allergic rhinitis, and one-third had a history of food allergies.
Dr. Blauvelt previously presented the primary results of CHRONOS without the new subgroup analysis at the American Academy of Dermatology 2017 meeting. The primary results were subsequently published (Lancet. 2017 Jun 10;389[10086]:2287-303). To recap, the bottom line: 39% of dupilumab-treated patients achieved an IGA score of 0/1 – that is, clear or almost clear – coupled with at least a 2-point improvement from baseline at week 16, versus 12% of controls on topical steroids plus placebo injections. That’s a strikingly impressive performance, according to the dermatologist.
“An IGA of 0/1 in AD is a very high bar. It tends to correlated with an EASI 90,” Dr. Blauvelt observed.
Rates of EASI 75 – meaning at least a 75% improvement from baseline EASI scores – were achieved in 64% of patients on weekly dupilumab plus topical steroids, 69% with dupilumab every 2 weeks plus topicals, and 23% on topical steroids plus placebo. These efficacy results were essentially mirrored at week 52, with no significant changes in response rates from week 16 to week 52.
In another new finding from CHRONOS presented by Dr. Blauvelt at the EADV congress, itch also improved sharply across the board in dupilumab-treated patients, regardless of their baseline demographic and other characteristics, meaning there’s no point for clinicians to reserve the biologic for selected subgroups of patients with moderate or severe AD. From a mean baseline score of 7.6 on the 10-point peak pruritus numerical rating scale, at least a 3-point improvement was achieved in 56% of patients on biweekly dupilumab plus topical steroids, 43% on weekly dupilumab and topical steroids, and in 16% on topical steroids plus placebo injections.
Of note, 84% of patients in the two dupilumab arms remained in the CHRONOS trial through the full 52 weeks. That’s a high retention rate for a 1-year study involving a disease with a major adverse quality of life impact. In contrast, only about two-thirds of controls on topical therapy plus placebo injections stuck with the study for the duration.
The high retention rate may have had much to do with dupilumab’s generally favorable safely profile, as seen not only in CHRONOS but in earlier trials. No new safety concerns arose during the 52-week study. The dupilumab and control groups had similar rates of most side effects, with just a few exceptions: nonherpetic skin infections and worsening AD occurred more frequently in controls on topical steroids alone, while mild injection site reactions were twice as common in patients who got dupilumab than in those who received placebo injections.
Also, conjunctivitis occurred in 14% of patients on weekly dupilumab and 19% with biweekly dupilumab, compared with 8% of controls. “To me, conjunctivitis is the only significant side effect for this drug that we’ve seen thus far,” Dr. Blauvelt commented. The mechanism of the conjunctivitis is unknown. It’s clear, however, that the rate goes up with duration on therapy.
“Most of the cases have been mild to moderate and have not interfered with therapy. I’ve treated probably 80 patients with dupilumab, and I’ve had only 1 who had to stop due to her eyes,” the dermatologist recalled. The condition often responds to wetting eye drops, although topical corticosteroid eye drops are required sometimes, he added.
CAFE was a double-blind, randomized, placebo-controlled trial including 325 European patients with moderate or severe AD, all of whom were on a mid-potency topical corticosteroid with or without a topical calcineurin inhibitor. Two-thirds had previously been on cyclosporine with poor results; the drug was contraindicated in the others. Participants were randomized to subcutaneous injections of dupilumab at 300 mg weekly or biweekly or to placebo injections.
The primary outcome – an EASI-75 response at 16 weeks – was achieved in 59% of patients on weekly dupilumab, 63% of those on biweekly dupilumab, and 30% of controls on topical steroids plus placebo injections, according to Dr. De Bruin-Weller of the University Medical Center at Utrecht, the Netherlands.
A clinically meaningful 4-point or greater improvement from baseline in the Dermatology Life Quality Index occurred at 16 weeks in 79% and 88% of patients on dupilumab weekly or biweekly, respectively, compared with 44% of controls.
And among the three-quarters of CAFE participants reporting baseline moderate or severe pain or discomfort from AD, 55% of those on weekly dupilumab had none at all as assessed by the EQ-5D Pain/Discomfort Questionnaire at week 16, as did 64% on dupilumab every 2 weeks and 28% of controls on topical steroids.
At the prestigious joint EADV/AAD session of the European congress, Lawrence F. Eichenfield, MD, hailed dupilumab as evidence that “the systemic therapy revolution in atopic dermatitis is certainly happening,” with a plethora of additional agents targeting various key disease pathways now working their way through the developmental pipeline.
A key remaining question about dupilumab is, what about the safety and efficacy of the drug in the pediatric population, for whom the drug is not currently approved? Separate phase 3 randomized trials addressing this issue are now enrolling 6- to 11-year-olds and 12- to 17-year-olds.
Dr. Eichenfield is optimistic about the outcomes of these ongoing pediatric trials on the basis of an open-label, phase 2a, proof of concept study in 6- to 17-year-olds presented in a late-breaking research session at the 2017 annual meeting of the AAD. The pharmacokinetics were very similar to those seen in adults. Moreover, EASI scores improved by 32%-51% after just a single, weight-based injection of dupilumab and by up to 70% following four consecutive weekly injections.
“This is very, very exciting information. Whether the drug could actually be disease modifying is obviously a big question for us in pediatric dermatology,” observed Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.
He highlighted two important safety considerations regarding dupilumab: patients on the biologic should not be given any live vaccines, and the same IL-4 and IL-13 cytokine pathways targeted by dupilumab in patients with AD also are key in other atopic and allergic diseases. Indeed, the biologic showed positive outcomes in a recent pivotal phase 3 clinical trial for patients with uncontrolled persistent asthma, and an application for an expanded indication for dupilumab in such patients is expected to be filed with the FDA later in 2017. Dupilumab is also in phase 3 for patients with nasal polyps and in phase 2 studies for eosinophilic esophagitis.
“One of the interesting things about dupilumab is that we in dermatology are going to be in a situation where we’re able to impact diseases other than the single disease that the medication has been approved for,” Dr. Eichenfield said.
However, until such time as dupilumab actually receives an expanded indication for asthma and the details of how best to use the biologic in AD patients with that comorbidity have been worked out, it’s important for dermatologists prescribing dupilumab in those dual-diagnosis patients to discuss with them the necessity of staying on their asthma medications even though their skin is much improved, they’re feeling good, and their asthma seems to be doing better. During the dupilumab clinical trials program for AD, a fatal asthma exacerbation occurred in a patient with comorbid asthma who stopped taking asthma medications, he noted.
The CHRONOS and CAFE trials were funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt, Dr. De Bruin-Weller, and Dr. Eichenfield reported serving as consultants to and researchers for those pharmaceutical companies and numerous others.
GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.
CHRONOS was a 14-country, 1-year, randomized, double-blind, placebo-controlled, phase 3 clinical trial in which 740 adults with moderate to very severe AD were assigned to mid-potency topical corticosteroids along with topical calcineurin inhibitors as needed in steroid-sensitive locations, then randomized 3:1:3 to either subcutaneous dupilumab (Dupixent) at 300 mg once weekly, placebo injections, or dupilumab at 300 mg every 2 weeks on top of the topical therapy.
Dupilumab, a fully human monoclonal antibody, was approved by the Food and Drug Administration in March 2017 at a loading dose of 600 mg, followed by 300 mg every 2 weeks for treatment of adults with moderate to severe AD. The biologic agent is soon expected to be approved across the European Union as well. CHRONOS was the first major trial designed to replicate how the biologic would likely be utilized in real-world clinical practice: that is, in conjunction with rather than as an alternative to topical therapy. Earlier pivotal phase 3 trials were required by regulatory agencies to pit dupilumab monotherapy against placebo.
CHRONOS participants were “a very tough crowd, so to speak,” the dermatologist recalled. Their median body surface area of involvement was a whopping 55%, 60% were men, the median baseline EASI (Eczema Area and Severity Index) score was 30, and fully half of patients had an IGA (Investigator’s Global Assessment) score of 4, indicative of severe disease. Plus, comorbid atopic/allergic diseases were common: half of subjects had a history of asthma, nearly half had a history of allergic rhinitis, and one-third had a history of food allergies.
Dr. Blauvelt previously presented the primary results of CHRONOS without the new subgroup analysis at the American Academy of Dermatology 2017 meeting. The primary results were subsequently published (Lancet. 2017 Jun 10;389[10086]:2287-303). To recap, the bottom line: 39% of dupilumab-treated patients achieved an IGA score of 0/1 – that is, clear or almost clear – coupled with at least a 2-point improvement from baseline at week 16, versus 12% of controls on topical steroids plus placebo injections. That’s a strikingly impressive performance, according to the dermatologist.
“An IGA of 0/1 in AD is a very high bar. It tends to correlated with an EASI 90,” Dr. Blauvelt observed.
Rates of EASI 75 – meaning at least a 75% improvement from baseline EASI scores – were achieved in 64% of patients on weekly dupilumab plus topical steroids, 69% with dupilumab every 2 weeks plus topicals, and 23% on topical steroids plus placebo. These efficacy results were essentially mirrored at week 52, with no significant changes in response rates from week 16 to week 52.
In another new finding from CHRONOS presented by Dr. Blauvelt at the EADV congress, itch also improved sharply across the board in dupilumab-treated patients, regardless of their baseline demographic and other characteristics, meaning there’s no point for clinicians to reserve the biologic for selected subgroups of patients with moderate or severe AD. From a mean baseline score of 7.6 on the 10-point peak pruritus numerical rating scale, at least a 3-point improvement was achieved in 56% of patients on biweekly dupilumab plus topical steroids, 43% on weekly dupilumab and topical steroids, and in 16% on topical steroids plus placebo injections.
Of note, 84% of patients in the two dupilumab arms remained in the CHRONOS trial through the full 52 weeks. That’s a high retention rate for a 1-year study involving a disease with a major adverse quality of life impact. In contrast, only about two-thirds of controls on topical therapy plus placebo injections stuck with the study for the duration.
The high retention rate may have had much to do with dupilumab’s generally favorable safely profile, as seen not only in CHRONOS but in earlier trials. No new safety concerns arose during the 52-week study. The dupilumab and control groups had similar rates of most side effects, with just a few exceptions: nonherpetic skin infections and worsening AD occurred more frequently in controls on topical steroids alone, while mild injection site reactions were twice as common in patients who got dupilumab than in those who received placebo injections.
Also, conjunctivitis occurred in 14% of patients on weekly dupilumab and 19% with biweekly dupilumab, compared with 8% of controls. “To me, conjunctivitis is the only significant side effect for this drug that we’ve seen thus far,” Dr. Blauvelt commented. The mechanism of the conjunctivitis is unknown. It’s clear, however, that the rate goes up with duration on therapy.
“Most of the cases have been mild to moderate and have not interfered with therapy. I’ve treated probably 80 patients with dupilumab, and I’ve had only 1 who had to stop due to her eyes,” the dermatologist recalled. The condition often responds to wetting eye drops, although topical corticosteroid eye drops are required sometimes, he added.
CAFE was a double-blind, randomized, placebo-controlled trial including 325 European patients with moderate or severe AD, all of whom were on a mid-potency topical corticosteroid with or without a topical calcineurin inhibitor. Two-thirds had previously been on cyclosporine with poor results; the drug was contraindicated in the others. Participants were randomized to subcutaneous injections of dupilumab at 300 mg weekly or biweekly or to placebo injections.
The primary outcome – an EASI-75 response at 16 weeks – was achieved in 59% of patients on weekly dupilumab, 63% of those on biweekly dupilumab, and 30% of controls on topical steroids plus placebo injections, according to Dr. De Bruin-Weller of the University Medical Center at Utrecht, the Netherlands.
A clinically meaningful 4-point or greater improvement from baseline in the Dermatology Life Quality Index occurred at 16 weeks in 79% and 88% of patients on dupilumab weekly or biweekly, respectively, compared with 44% of controls.
And among the three-quarters of CAFE participants reporting baseline moderate or severe pain or discomfort from AD, 55% of those on weekly dupilumab had none at all as assessed by the EQ-5D Pain/Discomfort Questionnaire at week 16, as did 64% on dupilumab every 2 weeks and 28% of controls on topical steroids.
At the prestigious joint EADV/AAD session of the European congress, Lawrence F. Eichenfield, MD, hailed dupilumab as evidence that “the systemic therapy revolution in atopic dermatitis is certainly happening,” with a plethora of additional agents targeting various key disease pathways now working their way through the developmental pipeline.
A key remaining question about dupilumab is, what about the safety and efficacy of the drug in the pediatric population, for whom the drug is not currently approved? Separate phase 3 randomized trials addressing this issue are now enrolling 6- to 11-year-olds and 12- to 17-year-olds.
Dr. Eichenfield is optimistic about the outcomes of these ongoing pediatric trials on the basis of an open-label, phase 2a, proof of concept study in 6- to 17-year-olds presented in a late-breaking research session at the 2017 annual meeting of the AAD. The pharmacokinetics were very similar to those seen in adults. Moreover, EASI scores improved by 32%-51% after just a single, weight-based injection of dupilumab and by up to 70% following four consecutive weekly injections.
“This is very, very exciting information. Whether the drug could actually be disease modifying is obviously a big question for us in pediatric dermatology,” observed Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.
He highlighted two important safety considerations regarding dupilumab: patients on the biologic should not be given any live vaccines, and the same IL-4 and IL-13 cytokine pathways targeted by dupilumab in patients with AD also are key in other atopic and allergic diseases. Indeed, the biologic showed positive outcomes in a recent pivotal phase 3 clinical trial for patients with uncontrolled persistent asthma, and an application for an expanded indication for dupilumab in such patients is expected to be filed with the FDA later in 2017. Dupilumab is also in phase 3 for patients with nasal polyps and in phase 2 studies for eosinophilic esophagitis.
“One of the interesting things about dupilumab is that we in dermatology are going to be in a situation where we’re able to impact diseases other than the single disease that the medication has been approved for,” Dr. Eichenfield said.
However, until such time as dupilumab actually receives an expanded indication for asthma and the details of how best to use the biologic in AD patients with that comorbidity have been worked out, it’s important for dermatologists prescribing dupilumab in those dual-diagnosis patients to discuss with them the necessity of staying on their asthma medications even though their skin is much improved, they’re feeling good, and their asthma seems to be doing better. During the dupilumab clinical trials program for AD, a fatal asthma exacerbation occurred in a patient with comorbid asthma who stopped taking asthma medications, he noted.
The CHRONOS and CAFE trials were funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt, Dr. De Bruin-Weller, and Dr. Eichenfield reported serving as consultants to and researchers for those pharmaceutical companies and numerous others.
GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.
CHRONOS was a 14-country, 1-year, randomized, double-blind, placebo-controlled, phase 3 clinical trial in which 740 adults with moderate to very severe AD were assigned to mid-potency topical corticosteroids along with topical calcineurin inhibitors as needed in steroid-sensitive locations, then randomized 3:1:3 to either subcutaneous dupilumab (Dupixent) at 300 mg once weekly, placebo injections, or dupilumab at 300 mg every 2 weeks on top of the topical therapy.
Dupilumab, a fully human monoclonal antibody, was approved by the Food and Drug Administration in March 2017 at a loading dose of 600 mg, followed by 300 mg every 2 weeks for treatment of adults with moderate to severe AD. The biologic agent is soon expected to be approved across the European Union as well. CHRONOS was the first major trial designed to replicate how the biologic would likely be utilized in real-world clinical practice: that is, in conjunction with rather than as an alternative to topical therapy. Earlier pivotal phase 3 trials were required by regulatory agencies to pit dupilumab monotherapy against placebo.
CHRONOS participants were “a very tough crowd, so to speak,” the dermatologist recalled. Their median body surface area of involvement was a whopping 55%, 60% were men, the median baseline EASI (Eczema Area and Severity Index) score was 30, and fully half of patients had an IGA (Investigator’s Global Assessment) score of 4, indicative of severe disease. Plus, comorbid atopic/allergic diseases were common: half of subjects had a history of asthma, nearly half had a history of allergic rhinitis, and one-third had a history of food allergies.
Dr. Blauvelt previously presented the primary results of CHRONOS without the new subgroup analysis at the American Academy of Dermatology 2017 meeting. The primary results were subsequently published (Lancet. 2017 Jun 10;389[10086]:2287-303). To recap, the bottom line: 39% of dupilumab-treated patients achieved an IGA score of 0/1 – that is, clear or almost clear – coupled with at least a 2-point improvement from baseline at week 16, versus 12% of controls on topical steroids plus placebo injections. That’s a strikingly impressive performance, according to the dermatologist.
“An IGA of 0/1 in AD is a very high bar. It tends to correlated with an EASI 90,” Dr. Blauvelt observed.
Rates of EASI 75 – meaning at least a 75% improvement from baseline EASI scores – were achieved in 64% of patients on weekly dupilumab plus topical steroids, 69% with dupilumab every 2 weeks plus topicals, and 23% on topical steroids plus placebo. These efficacy results were essentially mirrored at week 52, with no significant changes in response rates from week 16 to week 52.
In another new finding from CHRONOS presented by Dr. Blauvelt at the EADV congress, itch also improved sharply across the board in dupilumab-treated patients, regardless of their baseline demographic and other characteristics, meaning there’s no point for clinicians to reserve the biologic for selected subgroups of patients with moderate or severe AD. From a mean baseline score of 7.6 on the 10-point peak pruritus numerical rating scale, at least a 3-point improvement was achieved in 56% of patients on biweekly dupilumab plus topical steroids, 43% on weekly dupilumab and topical steroids, and in 16% on topical steroids plus placebo injections.
Of note, 84% of patients in the two dupilumab arms remained in the CHRONOS trial through the full 52 weeks. That’s a high retention rate for a 1-year study involving a disease with a major adverse quality of life impact. In contrast, only about two-thirds of controls on topical therapy plus placebo injections stuck with the study for the duration.
The high retention rate may have had much to do with dupilumab’s generally favorable safely profile, as seen not only in CHRONOS but in earlier trials. No new safety concerns arose during the 52-week study. The dupilumab and control groups had similar rates of most side effects, with just a few exceptions: nonherpetic skin infections and worsening AD occurred more frequently in controls on topical steroids alone, while mild injection site reactions were twice as common in patients who got dupilumab than in those who received placebo injections.
Also, conjunctivitis occurred in 14% of patients on weekly dupilumab and 19% with biweekly dupilumab, compared with 8% of controls. “To me, conjunctivitis is the only significant side effect for this drug that we’ve seen thus far,” Dr. Blauvelt commented. The mechanism of the conjunctivitis is unknown. It’s clear, however, that the rate goes up with duration on therapy.
“Most of the cases have been mild to moderate and have not interfered with therapy. I’ve treated probably 80 patients with dupilumab, and I’ve had only 1 who had to stop due to her eyes,” the dermatologist recalled. The condition often responds to wetting eye drops, although topical corticosteroid eye drops are required sometimes, he added.
CAFE was a double-blind, randomized, placebo-controlled trial including 325 European patients with moderate or severe AD, all of whom were on a mid-potency topical corticosteroid with or without a topical calcineurin inhibitor. Two-thirds had previously been on cyclosporine with poor results; the drug was contraindicated in the others. Participants were randomized to subcutaneous injections of dupilumab at 300 mg weekly or biweekly or to placebo injections.
The primary outcome – an EASI-75 response at 16 weeks – was achieved in 59% of patients on weekly dupilumab, 63% of those on biweekly dupilumab, and 30% of controls on topical steroids plus placebo injections, according to Dr. De Bruin-Weller of the University Medical Center at Utrecht, the Netherlands.
A clinically meaningful 4-point or greater improvement from baseline in the Dermatology Life Quality Index occurred at 16 weeks in 79% and 88% of patients on dupilumab weekly or biweekly, respectively, compared with 44% of controls.
And among the three-quarters of CAFE participants reporting baseline moderate or severe pain or discomfort from AD, 55% of those on weekly dupilumab had none at all as assessed by the EQ-5D Pain/Discomfort Questionnaire at week 16, as did 64% on dupilumab every 2 weeks and 28% of controls on topical steroids.
At the prestigious joint EADV/AAD session of the European congress, Lawrence F. Eichenfield, MD, hailed dupilumab as evidence that “the systemic therapy revolution in atopic dermatitis is certainly happening,” with a plethora of additional agents targeting various key disease pathways now working their way through the developmental pipeline.
A key remaining question about dupilumab is, what about the safety and efficacy of the drug in the pediatric population, for whom the drug is not currently approved? Separate phase 3 randomized trials addressing this issue are now enrolling 6- to 11-year-olds and 12- to 17-year-olds.
Dr. Eichenfield is optimistic about the outcomes of these ongoing pediatric trials on the basis of an open-label, phase 2a, proof of concept study in 6- to 17-year-olds presented in a late-breaking research session at the 2017 annual meeting of the AAD. The pharmacokinetics were very similar to those seen in adults. Moreover, EASI scores improved by 32%-51% after just a single, weight-based injection of dupilumab and by up to 70% following four consecutive weekly injections.
“This is very, very exciting information. Whether the drug could actually be disease modifying is obviously a big question for us in pediatric dermatology,” observed Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego.
He highlighted two important safety considerations regarding dupilumab: patients on the biologic should not be given any live vaccines, and the same IL-4 and IL-13 cytokine pathways targeted by dupilumab in patients with AD also are key in other atopic and allergic diseases. Indeed, the biologic showed positive outcomes in a recent pivotal phase 3 clinical trial for patients with uncontrolled persistent asthma, and an application for an expanded indication for dupilumab in such patients is expected to be filed with the FDA later in 2017. Dupilumab is also in phase 3 for patients with nasal polyps and in phase 2 studies for eosinophilic esophagitis.
“One of the interesting things about dupilumab is that we in dermatology are going to be in a situation where we’re able to impact diseases other than the single disease that the medication has been approved for,” Dr. Eichenfield said.
However, until such time as dupilumab actually receives an expanded indication for asthma and the details of how best to use the biologic in AD patients with that comorbidity have been worked out, it’s important for dermatologists prescribing dupilumab in those dual-diagnosis patients to discuss with them the necessity of staying on their asthma medications even though their skin is much improved, they’re feeling good, and their asthma seems to be doing better. During the dupilumab clinical trials program for AD, a fatal asthma exacerbation occurred in a patient with comorbid asthma who stopped taking asthma medications, he noted.
The CHRONOS and CAFE trials were funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt, Dr. De Bruin-Weller, and Dr. Eichenfield reported serving as consultants to and researchers for those pharmaceutical companies and numerous others.
EXPERT ANALYSIS FROM THE EADV CONGRESS
Opioid-Related Hospitalizations Rising Faster Among Women
The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.
The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.
Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.
In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.
The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.
The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.
Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.
In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.
The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.
The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.
Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.
In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.
Team creates guidelines on CAR T-cell-related toxicity
Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.
The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.
“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.
Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.
The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:
- Baseline brain MRI to rule out central nervous system disease
- Cardiac monitoring starting on the day of CAR T‑cell infusion
- Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
- Assessing and grading CRS at least twice daily and whenever the patient’s status changes
- Assessing and grading CRES at least every 8 hours.
CRS
One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.
The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.
The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.
The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).
The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.
The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.
CRES
One section of the guidelines is dedicated to the grading and treatment of CRES, which typically manifests as a toxic encephalopathy.
The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, aphasia, somnolence, and tremors.
Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracranial pressure, papilledema, and cerebral edema.
Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.
The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)
CARTOX-10 is a 10-point test in which patients are asked to do the following:
- Name the current month (1 point) and year (1 point)
- Name the city (1 point) and hospital they are in (1 point)
- Name the president/prime minister of their home country (1 point)
- Name 3 nearby objects (3 points)
- Write a standard sentence (1 point)
- Count backward from 100 by tens (1 point).
A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.
Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.
Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies. 
Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.
The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.
“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.
Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.
The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:
- Baseline brain MRI to rule out central nervous system disease
- Cardiac monitoring starting on the day of CAR T‑cell infusion
- Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
- Assessing and grading CRS at least twice daily and whenever the patient’s status changes
- Assessing and grading CRES at least every 8 hours.
CRS
One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.
The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.
The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.
The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).
The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.
The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.
CRES
One section of the guidelines is dedicated to the grading and treatment of CRES, which typically manifests as a toxic encephalopathy.
The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, aphasia, somnolence, and tremors.
Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracranial pressure, papilledema, and cerebral edema.
Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.
The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)
CARTOX-10 is a 10-point test in which patients are asked to do the following:
- Name the current month (1 point) and year (1 point)
- Name the city (1 point) and hospital they are in (1 point)
- Name the president/prime minister of their home country (1 point)
- Name 3 nearby objects (3 points)
- Write a standard sentence (1 point)
- Count backward from 100 by tens (1 point).
A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.
Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.
Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.
Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.
The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.
“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.
Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.
The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:
- Baseline brain MRI to rule out central nervous system disease
- Cardiac monitoring starting on the day of CAR T‑cell infusion
- Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
- Assessing and grading CRS at least twice daily and whenever the patient’s status changes
- Assessing and grading CRES at least every 8 hours.
CRS
One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.
The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.
The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.
The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).
The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.
The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.
CRES
One section of the guidelines is dedicated to the grading and treatment of CRES, which typically manifests as a toxic encephalopathy.
The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, aphasia, somnolence, and tremors.
Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracranial pressure, papilledema, and cerebral edema.
Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.
The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)
CARTOX-10 is a 10-point test in which patients are asked to do the following:
- Name the current month (1 point) and year (1 point)
- Name the city (1 point) and hospital they are in (1 point)
- Name the president/prime minister of their home country (1 point)
- Name 3 nearby objects (3 points)
- Write a standard sentence (1 point)
- Count backward from 100 by tens (1 point).
A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.
Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.
Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.
Antibody shows early promise in AML/MDS trial
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
New toolkit can help nurses use genomics in patient care
The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.
The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.
The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.
“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.
“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”
The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.
A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.
The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.
The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.
The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.
“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.
“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”
The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.
A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.
The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.
The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.
The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.
“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.
“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”
The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.
A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.
Medial Oblique Meniscomeniscal Ligament
Arthroscopic identification and evaluation of the meniscomeniscal ligament.
Arthroscopic identification and evaluation of the meniscomeniscal ligament.
Arthroscopic identification and evaluation of the meniscomeniscal ligament.
FDA approves triple-therapy inhaler for COPD
The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.
Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.
“This approval represents a significant therapeutic convenience for those appropriate patients already on Breo Ellipta, that require additional bronchodilation or for those patients already on a combination of Breo Ellipta and Incruse Ellipta,” Mike Aguiar, CEO of Innoviva said in the press release.
In results supporting the FDA approval, the IMPACT study, a 52-week phase 3 clinical trial including 10,355 COPD patients sponsored by GSK, found that patients receiving Trelegy Ellipta experienced a 25% reduction in moderate to severe exacerbations compared to patients receiving Anoro Ellipta, and a 15% reduction in moderate to severe exacerbations, compared with patients receiving Relvar/Breo Ellipta. Change from baseline FEV1, change from baseline scores on the St George’s Respiratory Questionnaire, and time to first moderate/severe COPD exacerbation also were improved in the Trelegy Ellipta study group compared to the others.
“This is the first study to report a comparison of a single inhaler triple therapy with two dual therapies, providing much needed clinical evidence about the ability of a single inhaler triple therapy to reduce exacerbations,” Patrick Vallance, President of R&D at GSK, noted in a press release announcing the results of the IMPACT study.
The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.
Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.
“This approval represents a significant therapeutic convenience for those appropriate patients already on Breo Ellipta, that require additional bronchodilation or for those patients already on a combination of Breo Ellipta and Incruse Ellipta,” Mike Aguiar, CEO of Innoviva said in the press release.
In results supporting the FDA approval, the IMPACT study, a 52-week phase 3 clinical trial including 10,355 COPD patients sponsored by GSK, found that patients receiving Trelegy Ellipta experienced a 25% reduction in moderate to severe exacerbations compared to patients receiving Anoro Ellipta, and a 15% reduction in moderate to severe exacerbations, compared with patients receiving Relvar/Breo Ellipta. Change from baseline FEV1, change from baseline scores on the St George’s Respiratory Questionnaire, and time to first moderate/severe COPD exacerbation also were improved in the Trelegy Ellipta study group compared to the others.
“This is the first study to report a comparison of a single inhaler triple therapy with two dual therapies, providing much needed clinical evidence about the ability of a single inhaler triple therapy to reduce exacerbations,” Patrick Vallance, President of R&D at GSK, noted in a press release announcing the results of the IMPACT study.
The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.
Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.
“This approval represents a significant therapeutic convenience for those appropriate patients already on Breo Ellipta, that require additional bronchodilation or for those patients already on a combination of Breo Ellipta and Incruse Ellipta,” Mike Aguiar, CEO of Innoviva said in the press release.
In results supporting the FDA approval, the IMPACT study, a 52-week phase 3 clinical trial including 10,355 COPD patients sponsored by GSK, found that patients receiving Trelegy Ellipta experienced a 25% reduction in moderate to severe exacerbations compared to patients receiving Anoro Ellipta, and a 15% reduction in moderate to severe exacerbations, compared with patients receiving Relvar/Breo Ellipta. Change from baseline FEV1, change from baseline scores on the St George’s Respiratory Questionnaire, and time to first moderate/severe COPD exacerbation also were improved in the Trelegy Ellipta study group compared to the others.
“This is the first study to report a comparison of a single inhaler triple therapy with two dual therapies, providing much needed clinical evidence about the ability of a single inhaler triple therapy to reduce exacerbations,” Patrick Vallance, President of R&D at GSK, noted in a press release announcing the results of the IMPACT study.
VIDEO: Educational intervention boosts A fib anticoagulation
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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On Twitter @mitchelzoler
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Anticoagulation rose by 12 percentage points from baseline with intervention and by 3 percentage points among controls.
Data source: IMPACT AF, which randomized 2,281 AF patients for 1 year at 48 centers in five middle-income countries.
Disclosures: IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
E-cigarettes most popular among youngest adults
Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.
When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).
Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.
When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).
Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.
When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).
FROM MMWR