The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

Dear colleagues,

The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.

AGA Institute

The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.

As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.

This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.

Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?

Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.

For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.

If you have interest in contributing or have ideas for future TNG topics, please contact me (vijayarao@medicine.bsd.uchicago.edu), or Ryan Farrell (rfarrell@gastro.org), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition

Dear colleagues,

The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.

AGA Institute

The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.

As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.

This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.

Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?

Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.

For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.

If you have interest in contributing or have ideas for future TNG topics, please contact me (vijayarao@medicine.bsd.uchicago.edu), or Ryan Farrell (rfarrell@gastro.org), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition

Dear colleagues,

The August issue of The New Gastroenterologist has arrived! The summer of 2020 certainly looks different from years past, as the COVID-19 pandemic rages on and we continue to adjust to the new realities of our personal and professional lives. Our third-year fellows have graduated amidst these unusual circumstances, some facing an uncertain job landscape. Yet their hard work is not lost upon us – as we must step back to recognize their achievements and bid them congratulations on the culmination of several years of training.

AGA Institute

The pandemic has been pervasive in medical education with a profound effect on our training programs. Two very resourceful fellows, Indira Bhavsar-Burke and Claire Jansson-Knodell (Indiana University), share their experience with COVID-19 and how they used this time to create an online curriculum for medical students who were pulled from their gastroenterology clinical rotations.

As we remain socially distanced, connecting through virtual platforms and social media seems more important than ever, but digital media can be difficult to navigate as physicians. Austin Chiang (Thomas Jefferson University) offers a candid snapshot of the benefits and pitfalls of social media as a gastroenterologist, with advice on how to optimize one’s professional presence online.

This quarter’s “In Focus” feature is an excellent, high-yield review of eosinophilic esophagitis. Ronak Vashi Patel and Ikuo Hirano (Northwestern University) seek to answer frequently asked questions about diagnostic considerations and the approach to management by reviewing therapeutic options – a truly valuable clinical piece to guide any young gastroenterologist.

Our medical ethics series features a poignant piece written by Diana Anderson (University of California, San Francisco) and David Seres (Columbia University) on the role of nutritional support in patients with restrictive eating disorders. The article addresses the complex interplay between certain diagnoses and our emotive response as clinicians – a critical piece of patient care that is seldom discussed. The authors implore us to consider this difficult question: Could our unconscious partiality as physicians be worse than intentional harm?

Adjoa Anyane-Yeboa (Harvard University) discusses how her interest in health equity and health care policy led her to the Commonwealth Fund Fellowship in Minority Health Policy. Her passion for health care delivery reform and the care of vulnerable populations shines through as she describes how this post-GI fellowship pathway has been formative in shaping her career as a dynamic new gastroenterologist.

For those interested in serving as an expert witness, seasoned malpractice attorneys Daniel Mills and Courtney Lindbert (Cunningham, Meyer & Vedrine P.C.) offer a salient list of the “do’s and don’ts” of the medical expert. Finally, this summer’s DHPA Private Practice Perspectives article, written by Michael Weinstein (Capital Digestive Care), offers important considerations for evaluating independent GI practices and how their response to COVID-19 can dictate their preparedness for future crises.

If you have interest in contributing or have ideas for future TNG topics, please contact me (vijayarao@medicine.bsd.uchicago.edu), or Ryan Farrell (rfarrell@gastro.org), managing editor of TNG.
 

Stay well,

Vijaya L. Rao, MD
Editor-in-Chief
Assistant professor of medicine, University of Chicago, section of gastroenterology, hepatology & nutrition

The top three contact allergens in patients younger than 18 years of age are hydroperoxides of linalool, nickel sulfate, and methylisothiazolinone, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.

The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”

To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.

For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.

The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).

Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).

The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).

“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”

The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.

dbrunk@mdedge.com

The top three contact allergens in patients younger than 18 years of age are hydroperoxides of linalool, nickel sulfate, and methylisothiazolinone, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.

The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”

To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.

For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.

The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).

Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).

The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).

“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”

The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.

dbrunk@mdedge.com

The top three contact allergens in patients younger than 18 years of age are hydroperoxides of linalool, nickel sulfate, and methylisothiazolinone, according to an analysis of data from the Pediatric Allergic Contact Dermatitis Registry.

The registry is the first multicenter prospective database in the United States with a focus on pediatric allergic contact dermatitis. JiaDe (Jeff) Yu, MD, a dermatologist at Massachusetts General Hospital, Boston, was awarded a Dermatology Foundation Career Development Grant and formed the registry in 2018 “in an effort to gain a better understanding of allergic contact dermatitis in children,” Idy Tam, MS, said during the virtual annual meeting of the Society for Pediatric Dermatology. “There is currently limited data regarding the pediatric allergic contact dermatitis in the U.S., despite as many as 20% of children having allergic contact dermatitis.”

To date, the Pediatric Allergic Contact Dermatitis Registry consists of 10 academic medical centers with high volume pediatric patch testing across the United States: Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; the University of Missouri–Columbia; Stanford (Calif.) University; the Medical University of South Carolina, Charleston; Texas Children’s Hospital, Houston; Northwestern University, Chicago; Emory University, Atlanta; Washington University, St. Louis; and the University of California, San Diego.

For the current analysis, Ms. Tam, a research fellow in the department of dermatology at Massachusetts General Hospital, and colleagues collected data on 218 patients under age 18 who were referred for an evaluation of allergic contact dermatitis at one of the 10 participating sites between January 2016 and June 2020.

The mean age of children at the time of their patch testing was 10 years, 62% were girls, and 66% had a history of atopic dermatitis (AD). Most (75%) were White, 14% were Black, 6% were Asian, the rest were from other racial backgrounds. The distribution of dermatitis varied; the top five most commonly affected sites were the face (62%), arms (35%), legs (29%), hands (27%), and neck (20%).

Ms. Tam reported that the mean number of allergens patch tested per child was 78. In all, 81% of children had one or more positive patch test reactions, with a similar rate among those with and without a history of AD (80% vs. 82%, respectively; P = .21). The five most common allergens were hydroperoxides of linalool (22%), nickel sulfate (19%), methylisothiazolinone (17%), cobalt chloride (13%), and fragrance mix I (12%).

The top two treatments at the time of patch testing were a topical corticosteroid (78%) and a topical calcineurin inhibitor (26%).

“This study has allowed for the increased collaboration among dermatologists with expertise in pediatric dermatology and allergic contact dermatitis,” concluded Ms. Tam, a fourth-year medical student at Tufts University, Boston. “We continue to actively seek further collaboration with a goal of creating the most comprehensive pediatric allergic contact dermatitis registry, which can improve our understanding of this condition in children and hopefully guide future research in this field.”

The work was recognized as one of the top poster abstracts at the meeting. The researchers reported having no relevant disclosures.

dbrunk@mdedge.com

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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

For the fifth consecutive year, the Mayo Clinic in Rochester, Minnesota, claimed the number one spot in the annual honor roll of best hospitals, published today by US News & World Report.

This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.

“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.

“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.

“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.

Mayo Clinic Still Number One

Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”

Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.

Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.

2020–2021 Best Hospitals Honor Roll

1. Mayo Clinic, Rochester, Minnesota

2. Cleveland Clinic, Ohio

3. Johns Hopkins Hospital, Baltimore, Maryland

4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City

4. (tie) UCLA Medical Center, Los Angeles

6. Massachusetts General Hospital, Boston

7. Cedars-Sinai Medical Center, San Francisco

8. UCSF Medical Center, San Francisco

9. NYU Langone Hospitals, New York, New York City

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor

12. Brigham and Women’s Hospital, Boston

13. Stanford Health Care–Stanford Hospital, Palo Alto, California

14. Mount Sinai Hospital, New York City

15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

16. Mayo Clinic–Phoenix

17. Rush University Medical Center, Chicago

18. (tie) Barnes-Jewish Hospital, Saint Louis

18. (tie) Keck Hospital of USC, Los Angeles

20. Houston Methodist Hospital, Texas

In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.

For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.

Top Five for Cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York City

3. Mayo Clinic, Rochester, Minnesota

4. Johns Hopkins Hospital, Baltimore, Maryland

5. Cleveland Clinic, Ohio

 

Top Five for Cardiology and Heart Surgery

1. Cleveland Clinic, Ohio

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, NYC

5. Massachusetts General Hospital, Boston

 

Top Five for Orthopedics

1. Hospital for Special Surgery, New York City

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York City

5. Rush University Medical Center, Chicago

For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.

The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report on hospital ranking is available online.
 

This article first appeared on Medscape.com.

For the fifth consecutive year, the Mayo Clinic in Rochester, Minnesota, claimed the number one spot in the annual honor roll of best hospitals, published today by US News & World Report.

This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.

“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.

“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.

“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.

Mayo Clinic Still Number One

Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”

Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.

Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.

2020–2021 Best Hospitals Honor Roll

1. Mayo Clinic, Rochester, Minnesota

2. Cleveland Clinic, Ohio

3. Johns Hopkins Hospital, Baltimore, Maryland

4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City

4. (tie) UCLA Medical Center, Los Angeles

6. Massachusetts General Hospital, Boston

7. Cedars-Sinai Medical Center, San Francisco

8. UCSF Medical Center, San Francisco

9. NYU Langone Hospitals, New York, New York City

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor

12. Brigham and Women’s Hospital, Boston

13. Stanford Health Care–Stanford Hospital, Palo Alto, California

14. Mount Sinai Hospital, New York City

15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

16. Mayo Clinic–Phoenix

17. Rush University Medical Center, Chicago

18. (tie) Barnes-Jewish Hospital, Saint Louis

18. (tie) Keck Hospital of USC, Los Angeles

20. Houston Methodist Hospital, Texas

In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.

For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.

Top Five for Cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York City

3. Mayo Clinic, Rochester, Minnesota

4. Johns Hopkins Hospital, Baltimore, Maryland

5. Cleveland Clinic, Ohio

 

Top Five for Cardiology and Heart Surgery

1. Cleveland Clinic, Ohio

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, NYC

5. Massachusetts General Hospital, Boston

 

Top Five for Orthopedics

1. Hospital for Special Surgery, New York City

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York City

5. Rush University Medical Center, Chicago

For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.

The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report on hospital ranking is available online.
 

This article first appeared on Medscape.com.

For the fifth consecutive year, the Mayo Clinic in Rochester, Minnesota, claimed the number one spot in the annual honor roll of best hospitals, published today by US News & World Report.

This year’s rankings include special recognition of the “herculean efforts” by the nation’s healthcare professionals in fighting COVID-19, often at great personal risk.

“The US News Hospital Heroes series is a cornerstone of this year’s rankings package, profiling more than 65 health care heroes from across the country, along with commentary from top executives at hospitals who faced the pandemic head on,” a news release from the magazine explains.

“The pandemic has altered, perhaps permanently, how patients get care and from whom they get it. Amid the disruption, we are steadfastly committed to providing the public with authoritative data for comparing hospital quality,” Ben Harder, managing editor and chief of health analysis at US News, said in the release.

“No hospital’s clinical team came through this unprecedented health crisis unscathed. Our Hospital Heroes series is a tribute to recognizing individuals at urban and rural hospitals in communities across the country who have gone above and beyond during this unparalleled time in history,” said Harder.

Mayo Clinic Still Number One

Following Mayo Clinic, Cleveland Clinic in Ohio takes the number two spot this year (up from number four last year) in the magazine’s annual honor roll, which highlights hospitals that deliver “exceptional treatment across multiple areas of care.”

Johns Hopkins Hospital in Baltimore, Maryland, holds the number three spot, while New York-Presbyterian Hospital–Columbia and Cornell in New York City and UCLA Medical Center, Los Angeles, tie for the number four spot.

Massachusetts General Hospital in Boston, which held the number two spot last year, has fallen to number six. Rounding out the top 10, in order, are Cedars-Sinai Medical Center, Los Angeles; UCSF Medical Center, San Francisco; NYU Langone Hospitals, New York City; Northwestern Memorial Hospital, Chicago, Illinois.

2020–2021 Best Hospitals Honor Roll

1. Mayo Clinic, Rochester, Minnesota

2. Cleveland Clinic, Ohio

3. Johns Hopkins Hospital, Baltimore, Maryland

4. (tie) New York–Presbyterian Hospital–Columbia and Cornell, New York City

4. (tie) UCLA Medical Center, Los Angeles

6. Massachusetts General Hospital, Boston

7. Cedars-Sinai Medical Center, San Francisco

8. UCSF Medical Center, San Francisco

9. NYU Langone Hospitals, New York, New York City

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor

12. Brigham and Women’s Hospital, Boston

13. Stanford Health Care–Stanford Hospital, Palo Alto, California

14. Mount Sinai Hospital, New York City

15. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

16. Mayo Clinic–Phoenix

17. Rush University Medical Center, Chicago

18. (tie) Barnes-Jewish Hospital, Saint Louis

18. (tie) Keck Hospital of USC, Los Angeles

20. Houston Methodist Hospital, Texas

In the 2020–2021 Best Hospitals: Specialty Rankings, University of Texas MD Anderson Cancer Center continues to hold the number one spot in cancer, the Hospital for Special Surgery is number one in orthopedics, and the Cleveland Clinic is number one in cardiology and heart surgery.

For this year’s rankings, US News developed a new cardiac rating that measures the quality of hospitals› transcatheter aortic valve replacement, which is rapidly being adopted as a minimally invasive alternative to aortic valve surgery.

Top Five for Cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York City

3. Mayo Clinic, Rochester, Minnesota

4. Johns Hopkins Hospital, Baltimore, Maryland

5. Cleveland Clinic, Ohio

 

Top Five for Cardiology and Heart Surgery

1. Cleveland Clinic, Ohio

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, NYC

5. Massachusetts General Hospital, Boston

 

Top Five for Orthopedics

1. Hospital for Special Surgery, New York City

2. Mayo Clinic, Rochester, Minnesota

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York City

5. Rush University Medical Center, Chicago

For the 2020–2021 rankings and ratings, US News compared more than 4500 medical centers across the country in 16 specialties and 10 procedures and conditions. Of these, 563 were recognized as Best Regional Hospitals on the basis of their strong performance in multiple areas of care. The top 20 hospitals, which deliver exceptional treatment across many areas of care, were also named to the honor roll.

The magazine notes that data for the 2020–2021 Best Hospitals rankings and ratings come from a period predating the COVID-19 pandemic and were not affected by the pandemic’s impact on hospitals. The methodologies are based largely on objective measures, such as risk-adjusted survival and discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report on hospital ranking is available online.
 

This article first appeared on Medscape.com.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

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

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

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

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

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

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at obnews@mdedge.com.

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.

A secondary analysis of a major study of polypill therapy for hypertension found that patients who don’t reach blood pressure targets are less likely to have their medications adjusted if they’re on fixed-dose combination therapy.

However, hypertension patients on low-dose, triple-pill combination therapy are more likely to achieve blood pressure control than are those on usual care.

The secondary analysis of Triple Pill vs. Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) was published online in JAMA Cardiology (2020 Jul 22. doi: 10.1001/jamacardio.2020.2739). The trial randomized 700 patients with hypertension in Sri Lanka to triple-pill fixed-dose combination (FDC) therapy or usual care during February 2016–May 2017, with follow-up ending in October 2017.

A greater proportion of FDC patients reached target BP by the end of the study compared with usual care, 70% vs. 55%. However, the study found that therapeutic inertia – the failure to intensify therapy in nonresponsive patients – was more common in the FDC group at 6- and 12-week follow-up: 87% vs. 64% and 90% vs. 65%, respectively; both differences were significant different at P < .001).

The once-daily FDC pill contained telmisartan 20 mg, amlodipine 2.5 mg; and chlorthalidone 12.5 mg.

“Using a triple low-dose combination blood-pressure pill reduced the need to uptitrate BP therapy as more patients are at target, but doctors were less likely to uptitrate with triple-pill therapy when it was needed,” lead author Nelson Wang, MD, a research fellow at the George Institute for Global Health in suburban Sydney, said in an interview.

“Overall, there were fewer treatment inertia episodes in the triple-pill group than in the usual care group, but this was driven by the fact that fewer triple-pill patients needed uptitration when coming to their follow-up visits,” Dr. Wang added.

The analysis found that clinicians who prescribed triple-pill FDC used 23 unique drug treatment regimens per 100 treated patients compared with 54 different regiments with usual care (P < .001). “There was a large simplification in care,” Dr. Wang said of the FDC approach.

Dr. Wang and colleagues called for greater efforts to address therapeutic inertia, particularly with FDC therapies, and suggested potential strategies consisting of patient education, incentives for appropriate treatment adjustments, and feedback mechanisms and reminders for physicians.

“There may also be a need for more dosage options with the FDC triple pill to allow physicians to intensify therapy without fear of overtreatment and adverse drug effects,” they wrote.

In an accompanying editorial (JAMA Cardiol. 2020 Jul 22. doi: 10.1001/jamacardio.2020.2693), Ann Marie Navar, MD, PhD, associate professor of cardiology at Duke Clinical Research Institute, Durham, N.C., noted that initiating treatment with FDC therapy doesn’t preclude a more personalized approach for patients who don’t achieve their BP target. “The real choice now is the choice of initial treatment,” she wrote, adding that future treatment guidelines should consider extending an FDC-first approach to patients with less severe levels of hypertension.

“The study showed there’s room for a both a population-based fixed-drug combination approach and a personalized approach to how we think about hypertension management with fixed-dose therapy,” she said in an interview. “It’s not a one-and-done situation.”

Dr. Wang has no financial relationships to disclose. Study coauthors received funding from the Australian National Health and Medical Research Council and the U.K. National Institute for Health Research. Dr. Navar has no relevant financial relationships to report.

SOURCE: Wang N et al. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.2739.