User login
MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Should ctDNA guide clinical decisions in GI cancers?
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
FROM ASCO 2024
Rethinking Management of Skin Cancer in Older Patients
WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.
“ Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.
Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.
“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”
Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.
By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.
“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
NMSC Increasing in the Older Population
The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.
As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.
Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.
Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.
The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.
The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.
A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.
Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.
“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
Underutilized Management Options for NMSC
In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.
The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”
Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”
Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.
Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.
A Personal Story, a Word on Melanoma
Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.
The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.
“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”
Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.
With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.
“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”
Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.
A version of this article appeared on Medscape.com.
WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.
“ Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.
Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.
“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”
Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.
By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.
“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
NMSC Increasing in the Older Population
The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.
As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.
Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.
Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.
The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.
The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.
A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.
Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.
“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
Underutilized Management Options for NMSC
In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.
The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”
Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”
Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.
Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.
A Personal Story, a Word on Melanoma
Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.
The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.
“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”
Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.
With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.
“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”
Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.
A version of this article appeared on Medscape.com.
WASHINGTON — In 2013, Vishal A. Patel, MD, was completing a fellowship in Mohs surgery and cutaneous oncology at Columbia University Irving Medical Center, New York City, when a study was published showing that most nonmelanoma skin cancers (NMSCs) were treated with surgery, regardless of the patient’s life expectancy. Life expectancy “should enter into treatment decisions,” the authors concluded.
“ Dr. Patel recalled at the ElderDerm conference hosted by the Department of Dermatology at George Washington University, Washington, DC, and described as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.
Today, however, more than a decade later, guidelines still promote surgical therapy as the gold standard across the board, and questions raised by the study are still unaddressed, Dr. Patel, associate professor of dermatology and medicine/oncology at George Washington University, said at the meeting. These questions are becoming increasingly urgent as the incidence of skin cancer, especially NMSC, rises in the older adult population, especially in patients older than 85 years. “It’s a function of our training and our treatment guidelines that we reach for the most definitive treatment, which happens to be the most aggressive, in these patients,” added Dr. Patel, who is also director of the cutaneous oncology program at the GW Cancer Center.
“Sometimes we lose track of what ... we need to do” to provide care that reflects the best interests of the older patient, he continued. “Surgery may be the gold standard for treating the majority of NMSCs ... but is it the [best option] for what our older patients and patients with limited life expectancy need?”
Learning about what truly matters to the patient is a key element of the “age-friendly, whole-person care” that dermatologists must embrace as older adults become an increasingly large subset of their patient population, Christina Prather, MD, director and associate professor of geriatrics and palliative medicine at George Washington University, said at the meeting.
By 2040, projections are that the number of adults aged 85 years and older in the United States will be nearly quadruple the number in 2000, according to one estimate.
“We know that there are less than 6000 practicing geriatricians in the country ... [so the healthcare system] needs more of you who know how to bring an age-friendly approach to care,” Dr. Prather said. Dermatology is among the specialties that need to be “geriatricized.”
NMSC Increasing in the Older Population
The incidence of skin cancer is rising faster than that of any other cancer, Dr. Patel said. One window into the epidemiology, he said, comes from recently published data showing that an average of 6.1 million adults were treated each year for skin cancer during 2016-2018 (5.2 million of them for NMSC) — an increase from an average of 5.8 million annually in the 2012-2015 period. The data come from the Medical Expenditure Panel Survey (MEPS), which is conducted by the US Public Health Service through the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.
As a frame of reference, the average number of adults treated each year for nonskin cancers during these periods rose from 10.8 to 11.9 million, according to the 2023 MEPS data. “Skin cancer is about one-third of all cancers combined,” Dr. Patel said.
Not only is the incidence of NMSC significantly higher than that of melanoma but it also shows a more prominent aging trend. This was documented recently in a long-term observational study from Japan, in which researchers looked at the change in the median age of patients with NMSC and melanoma, compared with cancers of other organs, from 1991 to 2020 and found that NMSC had by far the greatest rise in median age, to a median age of 80 years in 2021.
Even more notable, Dr. Patel said, was a particularly marked increase in the number of patients with skin cancer aged 90 years and older. In 2021, this group of older adults accounted for 17% of patients receiving treatment for skin cancer at the Japanese hospital where the data were collected.
The 2013 study that stirred Dr. Patel as a fellow was of 1536 consecutive patients diagnosed with NMSC at two dermatology clinics (a University of California San Francisco–based private clinic and a Veterans Affairs Medical Center clinic) and followed for 6 years. “What’s interesting and worth thinking about is that, regardless of patients’ life expectancy, NMSCs were treated aggressively and surgically, and the choice of surgery was not influenced by the patient’s poor prognosis in a multivariate model” adjusted for tumor and patient characteristics, he said at the meeting.
The researchers defined limited life expectancy as either 85 years or older or having a Charleston Comorbidity Index ≥ 3. Approximately half of the patients with limited life expectancy died within 5 years, none of NMSC. Most patients with limited life expectancy were not often bothered by their tumors, and approximately one in five reported a treatment complication within 2 years. The 5-year tumor recurrence rate was 3.7%.
A more recent study looked at 1181 patients older than 85 years with NMSC referred for Mohs surgery. Almost all patients in the multicenter, prospective cohort study (91.3%) were treated with Mohs.
Treated patients were more likely to have facial tumors and higher functional status than those not treated with Mohs surgery, and the most common reasons provided by surgeons for proceeding with the surgery were a patient desire for a high cure rate (66%), higher functional status for age (57%), and high-risk tumor type (40%). Almost 42% of the referred patients were 89 years or older.
“Granted, [the reasons] are justified indications for surgery,” Dr. Patel said. Yet the study brings up the question of “whether we need to do Mohs surgery this frequently in elderly patients?” In an email after the meeting, he added, “it’s a question we may need to reconsider as the elderly population continues to increase and median age of NMSC rises.”
Underutilized Management Options for NMSC
In his practice, discussions of treatment options are preceded by a thorough discussion of the disease itself. Many lesions are low risk, and helping patients understand risks, as well as understanding what is important to the patient — especially those with limited life expectancy — will guide shared decision-making to choose the best treatment, Dr. Patel said at the meeting.
The dermatologist’s risk assessment — both staging and stratifying risk as it relates to specific outcomes such as recurrence, metastases, or death — takes on added importance in the older patient, he emphasized. “I think we underutilize the risk assessment.”
Also underutilized is the option of shave removal for low-risk squamous cell carcinomas and basal cell carcinomas, Dr. Patel said, noting that, in the National Comprehensive Cancer Network guidelines, “there’s an option for shave removal and nothing more if you have clear margins.”
Alternatively, disc excision with the initial biopsy can often be considered. “Having that intent to treat at the time of biopsy may be all that needs to be done” in older patients with obvious or highly suspicious lesions, he said.
Systemic immunotherapy has joined the treatment armamentarium for advanced basal cell carcinoma and advanced cutaneous squamous cell carcinoma, and if early, ongoing research of intralesional programmed cell death protein 1 inhibitor treatment advances, this could be another option for older adults in the future, Dr. Patel said. Targeting drug delivery directly to the tumor would lower the total dose, decrease systemic exposure, and could be used to avoid surgery for some groups of patients, such as those with limited life expectancy.
A Personal Story, a Word on Melanoma
Dr. Prather recalled when her 97-year-old grandfather had a skin lesion on his forehead removed, and a conversation he had with her mother about whether he really needed to have the procedure because he had cognitive impairment and was on oral anticoagulants.
The clinician “said it absolutely had to go. ... I can’t tell you how much his doctors’ visits and wound care consumed my family’s life for the next few years — for this thing that never quite healed,” she said.
“Was it necessary? The more I’ve learned over time is that it wasn’t,” Dr. Prather added. “We have to take time [with our older patients] and think critically. What is feasible? What makes the most sense? What is the most important thing I need to know about the patient?”
Also important, Dr. Patel noted, is the big-picture consideration of skin cancer treatment costs. The MEPS survey data showing the rising prevalence of skin cancer treatment also documented the economic burden: A nearly 30% increase in the average annual cost of treating NMSC from $5 billion in 2012-2015 to $6.5 billion in 2016-2018. (The average annual costs of treating melanoma decreased slightly.) “Skin cancer is a big drain on our limited resources,” he said.
With melanoma as well, dermatologists must think critically and holistically about the individual patient — and not have “a single view lens of the disease and how we treat the disease,” said Dr. Patel, urging the audience to read a “Sounding Board” article published in The New England Journal of Medicine in 2021. The article argued that there is overdiagnosis of cutaneous melanoma stemming from increased screening, falling clinical thresholds for biopsy, and falling pathological thresholds for labeling morphologic changes as cancer.
“There’s a diagnostic disconnect and a problem of overdiagnosis ... because we’re afraid to miss or make a mistake,” he said. “It leads to the question, do all lesions denoted as skin cancers need aggressive treatment? What does it mean for the patient in front of you?”
Dr. Patel reported receiving honoraria from Regeneron, Almirall, Biofrontera, Sun Pharma, and SkylineDx and serving on the speaker bureau of Regeneron and Almirall. He is chief medical officer for Lazarus AI and is cofounder of the Skin Cancer Outcomes consortium. Dr. Prather disclosed relationships with the National Institutes of Health, AHRQ, The Washington Home Foundation, and the Alzheimer’s Association.
A version of this article appeared on Medscape.com.
Nurse-Led Care for Gout Generates Best Uric Acid Control
VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.
“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.
The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.
The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.
“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.
A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.
Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.
Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.
At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.
(83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).
The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.
Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.
The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).
Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
Potential Advantages of Nurse-Led Care
Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.
“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.
“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.
Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.
Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.
Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.
“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.
The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.
The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.
“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.
A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.
Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.
Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.
At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.
(83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).
The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.
Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.
The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).
Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
Potential Advantages of Nurse-Led Care
Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.
“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.
“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.
Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.
Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.
Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.
“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.
The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.
The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.
“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.
A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.
Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.
Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.
At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.
(83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).
The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.
Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.
The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).
Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
Potential Advantages of Nurse-Led Care
Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.
“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.
“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.
Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.
Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.
Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM EULAR 2024
Why Do Investigational OA Drugs Need Better Trial Endpoints? Lorecivivint Serves as an Example
VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.
For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.
Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.
Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
OA Is Not a Cartilage-Only Disease
“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.
There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.
Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.
In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.
In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.
Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.
In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
New Follow-Up Data Support DMOAD Activity
Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.
The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.
Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.
In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.
At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
At 3 Years, Benefit Is Finally Potentially Significant
If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.
Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.
While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.
To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.
“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.
Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
A version of this article first appeared on Medscape.com.
VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.
For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.
Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.
Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
OA Is Not a Cartilage-Only Disease
“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.
There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.
Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.
In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.
In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.
Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.
In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
New Follow-Up Data Support DMOAD Activity
Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.
The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.
Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.
In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.
At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
At 3 Years, Benefit Is Finally Potentially Significant
If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.
Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.
While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.
To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.
“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.
Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
A version of this article first appeared on Medscape.com.
VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.
For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.
Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.
Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
OA Is Not a Cartilage-Only Disease
“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.
There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.
Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.
In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.
In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.
Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.
In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
New Follow-Up Data Support DMOAD Activity
Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.
The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.
Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.
In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.
At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
At 3 Years, Benefit Is Finally Potentially Significant
If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.
Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.
While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.
To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.
“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.
Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
A version of this article first appeared on Medscape.com.
FROM EULAR 2024
Ixekizumab Met Phase 3 Trial Endpoint in Juvenile PsA, Enthesitis-Related Arthritis
VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.
With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.
In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.
The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
Nearly 90% Achieve ACR30
The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.
The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.
When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.
Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).
An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.
Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.
In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.
On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
Ixekizumab Might Fulfill Need for More Options
There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.
Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.
While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.
Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.
With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.
In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.
The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
Nearly 90% Achieve ACR30
The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.
The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.
When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.
Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).
An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.
Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.
In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.
On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
Ixekizumab Might Fulfill Need for More Options
There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.
Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.
While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.
Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.
With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.
In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.
The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
Nearly 90% Achieve ACR30
The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.
The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.
When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.
Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).
An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.
Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.
In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.
On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
Ixekizumab Might Fulfill Need for More Options
There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.
Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.
While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.
Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM EULAR 2024
Are Primary Care Physicians the Answer to the US Headache Neurologist Shortage?
SAN DIEGO —
It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.
However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.
Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
First Contact
To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.
The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.
After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.
The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.
About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.
Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.
“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.
The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”
However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.
“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.
Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.
These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.
In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.
The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.
Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.
“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”
The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
Improved Diagnosis, Better Care
Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.
“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”
Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”
The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.
Dr. Minen serves on the First Contact advisory board.
A version of this article appeared on Medscape.com.
SAN DIEGO —
It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.
However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.
Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
First Contact
To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.
The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.
After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.
The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.
About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.
Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.
“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.
The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”
However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.
“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.
Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.
These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.
In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.
The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.
Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.
“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”
The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
Improved Diagnosis, Better Care
Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.
“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”
Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”
The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.
Dr. Minen serves on the First Contact advisory board.
A version of this article appeared on Medscape.com.
SAN DIEGO —
It is estimated that about 4 million PCP office visits annually are headache related, and that 52.8% of all migraine encounters occur in primary care settings.
However, PCPs aren’t always adequately trained in headache management and referral times to specialist care can be lengthy.
Data published in Headache show only 564 accredited headache specialists practice in the United States, but at least 3700 headache specialists are needed to treat those affected by migraine, with even more needed to address other disabling headache types such as tension-type headache and cluster headache. To keep up with population growth, it is estimated that the United States will require 4500 headache specialists by 2040.
First Contact
To tackle this specialist shortfall, the AHS developed the First Contact program with the aim of improving headache education in primary care and help alleviate at least some of the demand for specialist care.
The national program was rolled out in 2020 and 2021. The educational symposia were delivered to PCPs at multiple locations across the country. The initiative also included a comprehensive website with numerous support resources.
After participating in the initiative, attendees were surveyed about the value of the program, and the results were subsequently analyzed and presented at the annual meeting of the American Headache Society.
The analysis included 636 survey respondents, a 38% response rate. Almost all participants (96%) were MDs and DOs. The remainder included nurse practitioners, physician assistants, and dentists.
About 85.6% of respondents reported being completely or very confident in their ability to recognize and accurately diagnose headache disorders, and 81.3% said they were completely or very confident in their ability to create tailored treatment plans.
Just over 90% of participants reported they would implement practice changes as a result of the program. The most commonly cited change was the use of diagnostic tools such as the three-question Migraine ID screener, followed closely by consideration of prescribing triptans and reducing the use of unnecessary neuroimaging.
“Overall, there was a positive response to this type of educational programming and interest in ongoing education in addressing headache disorders with both pharmaceutical and non-pharmaceutical treatment options,” said Nisha Malhotra, MD, a resident at New York University (NYU) Langone Health, New York City, who presented the findings at the conference.
The fact that so many general practitioners were keen to use this easy-to-use screen [Migraine ID screener], which can pick up about 90% of people with migraine, is “great,” said study investigator Mia Minen, MD, associate professor and chief of headache research at NYU Langone Health. “I’m pleased primary care providers said they were considering implementing this simple tool.”
However, respondents also cited barriers to change. These included cost constraints (48.9%), insurance reimbursement issues (48.6%), and lack of time (45.3%). Dr. Malhotra noted these concerns are primarily related to workflow rather than knowledge gaps or lack of training.
“This is exciting in that there doesn’t seem to be an issue with education primarily but rather with the logistical issues that exist in the workflow in a primary care setting,” said Dr. Malhotra.
Participants also noted the need for other improvements. For example, they expressed interest in differentiating migraine from other headache types and having a better understanding of how and when to refer to specialists, said Dr. Malhotra.
These practitioners also want to know more about treatment options beyond first-line medications. “They were interested in understanding more advanced medication treatment options beyond just the typical triptan,” said Dr. Malhotra.
In addition, they want to become more skilled in non-pharmaceutical options such as occipital nerve blocks and in massage, acupuncture, and other complementary forms of migraine management, she said.
The study may be vulnerable to sampling bias as survey participants had just attended an educational symposium on headaches. “They were already, to some degree, interested in improving their knowledge on headache,” said Dr. Malhotra.
Another study limitation was that researchers didn’t conduct a pre-survey analysis to determine changes as a result of the symposia. And as the survey was conducted so close to the symposium, “it’s difficult to draw conclusions on the long-term effects,” she added.
“That being said, First Contact is one of the first national initiatives for primary care education, and thus far, it has been very well received.”
The next step is to continue expanding the program and to create a First Contact for women and First Contact for pediatrics, said Dr. Minen.
Improved Diagnosis, Better Care
Commenting on the initiative, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, who co-chaired the session where the survey results were presented, said it helps address the supply-demand imbalance in headache healthcare.
“Many, many people have headache disorders, and very few people are technically headache specialists, so we have to rely on our colleagues in primary care to help address the great need that’s out there for patients with headache disorders.”
Too many patients don’t get a proper diagnosis or appropriate treatment, said Dr. VanderPluym, so as time passes, “diseases can become more chronic and more refractory, and it affects people’s quality of life and productivity.”
The First Contact program, she said, helps increase providers’ comfort and confidence that they are providing the best patient care possible and lead to a reduction in the need for specialist referrals.
Dr. Minen serves on the First Contact advisory board.
A version of this article appeared on Medscape.com.
FROM AHS 2024
Migraine Linked to Cardiovascular Risk in Veterans Study
SAN DIEGO — , according to results from a retrospective analysis of Veterans Health Administration (VHA) data. Migraine was also linked to greater risk of cardiovascular disease, and the researchers found similar risk among both genders, with the exceptions of a larger stroke risk among women and larger risk of TIA among men.
Gender Matters
The research complements other studies, such as an analysis drawn from the Women’s Health Study, according to Alexandra Schwartz, a doctoral student at Yeshiva University, who presented the research at the annual meeting of the American Headache Society. That study found a 53% increased risk of stroke (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.02-2.31) among 17,531 female subjects between the ages of 25 and 42. Another, smaller study in 1,400 men drawn from the Physicians Health study found an increased risk of major cardiovascular events of 1.24 (P = .008). Previous studies have shown that around two-thirds of VHA patients with migraine are male. “Our population gives us this really unique opportunity to look at men with migraine,” Ms. Schwartz said in an interview.
The differential risk factors among men and women are tantalizing. “Gender likely matters in terms of how migraine and stroke are related, and a number of other cardiovascular diseases,” said Ms. Schwartz.
Migraine has long been considered a disease of women, but 6% of men experience the condition, making it important to understand how migraine might affect cardiovascular result in men. “We would expect that there could be different underlying mechanisms in this kind of relationship ... it is absolutely worth understanding the extent to which this disease might impact their risk of cardiovascular events,” senior author Elizabeth Seng, PhD, said in an interview. She is a professor at Yeshiva University and a research associate at Albert Einstein School of Medicine.
The researchers examined data from 2,006,905 veterans between 2008 and 2021, including 681,784 migraineurs (492,234 men; 189,430 women) and 1,325,121 controls (983,154 men; 341,967 women) that were matched based on age within a 5-year band, gender, race, ethnicity, and VHA site of care.
Among individuals diagnosed with migraine, there was an increased risk of ischemic stroke (odds ratio [OR], 2.7; 95% CI, 2.6-2.7), TIA (OR, 7.3; 95% CI, 6.8-7.7), cardiovascular disease (OR, 3.6; 95% CI, 3.5-3.6), acute myocardial infarction (OR, 1.7; 95% CI, 1.6-1.8), heart failure (OR, 1.3; 95% CI, 1.3-1.4), and unstable angina (OR, 2.7; 95% CI, 2.5-2.8). There was an association between migraine and a lower risk of hemorrhagic stroke (OR, 0.4; 95% CI, 0.4-0.5), but only in men. When the findings were analyzed by gender, the findings were generally similar with the exception of a statistically significant, larger risk of ischemic stroke in women (OR, 3.0 versus 2.6), and a trend toward greater risk of TIA in men (OR, 7.3 versus 6.5).
While the study lends unique insight due to the high proportion of men, it also comes with the limitation that the participants were veterans, and may therefore differ from the general population with respect to general health status and other characteristics, said Ms. Schwartz.
Another Piece of the Puzzle
The large number of men in the study is important, according to session moderator Laine Green, MD, who was asked for comment. “The biggest population that was studied with respect to cardiovascular risk was the Women’s Health Study, which was predominantly White nurses over time, and it is one of our biggest important pieces of information when it comes to cardiovascular risk, specifically looking at those with migraine who seem to have this doubling of their underlying stroke risk. Trying to get the same type of information from different populations is exquisitely helpful, because it’s long been thought that the risk for stroke and cardiovascular events seems to lie with females with aura. Knowing that there may be risk in other groups is important and part of the overall counseling that we do with patients,” said Dr. Green, assistant professor of neurology at Mayo Clinic Arizona.
The findings could hint at causal mechanisms, according to Dr. Seng. Preliminary analyses, not yet reported, suggest that age also plays a role in the relationship between migraine and cardiovascular risks. “I think that it’s important to [determine] to what extent migraine might back up the curve on the age-related timing of these events. Migraine peaks in the 40s, and that’s well before most of these cardiovascular events peak. We want to understand not just the cross-sectional relationships, which were large, but also the extent to which migraine may be having a differential impact on risk in different age bands,” said Dr. Seng.
Ms. Schwartz, Dr. Seng, and Dr. Green have no relevant financial disclosures.
SAN DIEGO — , according to results from a retrospective analysis of Veterans Health Administration (VHA) data. Migraine was also linked to greater risk of cardiovascular disease, and the researchers found similar risk among both genders, with the exceptions of a larger stroke risk among women and larger risk of TIA among men.
Gender Matters
The research complements other studies, such as an analysis drawn from the Women’s Health Study, according to Alexandra Schwartz, a doctoral student at Yeshiva University, who presented the research at the annual meeting of the American Headache Society. That study found a 53% increased risk of stroke (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.02-2.31) among 17,531 female subjects between the ages of 25 and 42. Another, smaller study in 1,400 men drawn from the Physicians Health study found an increased risk of major cardiovascular events of 1.24 (P = .008). Previous studies have shown that around two-thirds of VHA patients with migraine are male. “Our population gives us this really unique opportunity to look at men with migraine,” Ms. Schwartz said in an interview.
The differential risk factors among men and women are tantalizing. “Gender likely matters in terms of how migraine and stroke are related, and a number of other cardiovascular diseases,” said Ms. Schwartz.
Migraine has long been considered a disease of women, but 6% of men experience the condition, making it important to understand how migraine might affect cardiovascular result in men. “We would expect that there could be different underlying mechanisms in this kind of relationship ... it is absolutely worth understanding the extent to which this disease might impact their risk of cardiovascular events,” senior author Elizabeth Seng, PhD, said in an interview. She is a professor at Yeshiva University and a research associate at Albert Einstein School of Medicine.
The researchers examined data from 2,006,905 veterans between 2008 and 2021, including 681,784 migraineurs (492,234 men; 189,430 women) and 1,325,121 controls (983,154 men; 341,967 women) that were matched based on age within a 5-year band, gender, race, ethnicity, and VHA site of care.
Among individuals diagnosed with migraine, there was an increased risk of ischemic stroke (odds ratio [OR], 2.7; 95% CI, 2.6-2.7), TIA (OR, 7.3; 95% CI, 6.8-7.7), cardiovascular disease (OR, 3.6; 95% CI, 3.5-3.6), acute myocardial infarction (OR, 1.7; 95% CI, 1.6-1.8), heart failure (OR, 1.3; 95% CI, 1.3-1.4), and unstable angina (OR, 2.7; 95% CI, 2.5-2.8). There was an association between migraine and a lower risk of hemorrhagic stroke (OR, 0.4; 95% CI, 0.4-0.5), but only in men. When the findings were analyzed by gender, the findings were generally similar with the exception of a statistically significant, larger risk of ischemic stroke in women (OR, 3.0 versus 2.6), and a trend toward greater risk of TIA in men (OR, 7.3 versus 6.5).
While the study lends unique insight due to the high proportion of men, it also comes with the limitation that the participants were veterans, and may therefore differ from the general population with respect to general health status and other characteristics, said Ms. Schwartz.
Another Piece of the Puzzle
The large number of men in the study is important, according to session moderator Laine Green, MD, who was asked for comment. “The biggest population that was studied with respect to cardiovascular risk was the Women’s Health Study, which was predominantly White nurses over time, and it is one of our biggest important pieces of information when it comes to cardiovascular risk, specifically looking at those with migraine who seem to have this doubling of their underlying stroke risk. Trying to get the same type of information from different populations is exquisitely helpful, because it’s long been thought that the risk for stroke and cardiovascular events seems to lie with females with aura. Knowing that there may be risk in other groups is important and part of the overall counseling that we do with patients,” said Dr. Green, assistant professor of neurology at Mayo Clinic Arizona.
The findings could hint at causal mechanisms, according to Dr. Seng. Preliminary analyses, not yet reported, suggest that age also plays a role in the relationship between migraine and cardiovascular risks. “I think that it’s important to [determine] to what extent migraine might back up the curve on the age-related timing of these events. Migraine peaks in the 40s, and that’s well before most of these cardiovascular events peak. We want to understand not just the cross-sectional relationships, which were large, but also the extent to which migraine may be having a differential impact on risk in different age bands,” said Dr. Seng.
Ms. Schwartz, Dr. Seng, and Dr. Green have no relevant financial disclosures.
SAN DIEGO — , according to results from a retrospective analysis of Veterans Health Administration (VHA) data. Migraine was also linked to greater risk of cardiovascular disease, and the researchers found similar risk among both genders, with the exceptions of a larger stroke risk among women and larger risk of TIA among men.
Gender Matters
The research complements other studies, such as an analysis drawn from the Women’s Health Study, according to Alexandra Schwartz, a doctoral student at Yeshiva University, who presented the research at the annual meeting of the American Headache Society. That study found a 53% increased risk of stroke (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.02-2.31) among 17,531 female subjects between the ages of 25 and 42. Another, smaller study in 1,400 men drawn from the Physicians Health study found an increased risk of major cardiovascular events of 1.24 (P = .008). Previous studies have shown that around two-thirds of VHA patients with migraine are male. “Our population gives us this really unique opportunity to look at men with migraine,” Ms. Schwartz said in an interview.
The differential risk factors among men and women are tantalizing. “Gender likely matters in terms of how migraine and stroke are related, and a number of other cardiovascular diseases,” said Ms. Schwartz.
Migraine has long been considered a disease of women, but 6% of men experience the condition, making it important to understand how migraine might affect cardiovascular result in men. “We would expect that there could be different underlying mechanisms in this kind of relationship ... it is absolutely worth understanding the extent to which this disease might impact their risk of cardiovascular events,” senior author Elizabeth Seng, PhD, said in an interview. She is a professor at Yeshiva University and a research associate at Albert Einstein School of Medicine.
The researchers examined data from 2,006,905 veterans between 2008 and 2021, including 681,784 migraineurs (492,234 men; 189,430 women) and 1,325,121 controls (983,154 men; 341,967 women) that were matched based on age within a 5-year band, gender, race, ethnicity, and VHA site of care.
Among individuals diagnosed with migraine, there was an increased risk of ischemic stroke (odds ratio [OR], 2.7; 95% CI, 2.6-2.7), TIA (OR, 7.3; 95% CI, 6.8-7.7), cardiovascular disease (OR, 3.6; 95% CI, 3.5-3.6), acute myocardial infarction (OR, 1.7; 95% CI, 1.6-1.8), heart failure (OR, 1.3; 95% CI, 1.3-1.4), and unstable angina (OR, 2.7; 95% CI, 2.5-2.8). There was an association between migraine and a lower risk of hemorrhagic stroke (OR, 0.4; 95% CI, 0.4-0.5), but only in men. When the findings were analyzed by gender, the findings were generally similar with the exception of a statistically significant, larger risk of ischemic stroke in women (OR, 3.0 versus 2.6), and a trend toward greater risk of TIA in men (OR, 7.3 versus 6.5).
While the study lends unique insight due to the high proportion of men, it also comes with the limitation that the participants were veterans, and may therefore differ from the general population with respect to general health status and other characteristics, said Ms. Schwartz.
Another Piece of the Puzzle
The large number of men in the study is important, according to session moderator Laine Green, MD, who was asked for comment. “The biggest population that was studied with respect to cardiovascular risk was the Women’s Health Study, which was predominantly White nurses over time, and it is one of our biggest important pieces of information when it comes to cardiovascular risk, specifically looking at those with migraine who seem to have this doubling of their underlying stroke risk. Trying to get the same type of information from different populations is exquisitely helpful, because it’s long been thought that the risk for stroke and cardiovascular events seems to lie with females with aura. Knowing that there may be risk in other groups is important and part of the overall counseling that we do with patients,” said Dr. Green, assistant professor of neurology at Mayo Clinic Arizona.
The findings could hint at causal mechanisms, according to Dr. Seng. Preliminary analyses, not yet reported, suggest that age also plays a role in the relationship between migraine and cardiovascular risks. “I think that it’s important to [determine] to what extent migraine might back up the curve on the age-related timing of these events. Migraine peaks in the 40s, and that’s well before most of these cardiovascular events peak. We want to understand not just the cross-sectional relationships, which were large, but also the extent to which migraine may be having a differential impact on risk in different age bands,” said Dr. Seng.
Ms. Schwartz, Dr. Seng, and Dr. Green have no relevant financial disclosures.
FROM AHS 2024
Study Finds Major CV Event Risk in Patients With AD Similar to Controls
(RA), according to an analysis of national claims data.
The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.
To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.
Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
MACE Incidence, Relative Risk
The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).
In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).
MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
Unexpected Results
“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”
Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.
Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”
In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”
Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.
AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.
A version of this article appeared on Medscape.com.
(RA), according to an analysis of national claims data.
The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.
To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.
Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
MACE Incidence, Relative Risk
The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).
In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).
MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
Unexpected Results
“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”
Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.
Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”
In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”
Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.
AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.
A version of this article appeared on Medscape.com.
(RA), according to an analysis of national claims data.
The results of the analysis were presented during a poster session at the Revolutionizing Atopic Dermatitis conference in Chicago. “While it is known that atopic dermatitis is associated with some comorbidities, the specific risk of major adverse cardiovascular events in patients with AD, especially those with moderate to severe AD within the US population, is unclear,” the study’s first author Christopher G. Bunick, MD, PhD, said in an interview following the conference.
To characterize the risk for MACE in patients with AD vs matched controls without AD (non-AD) and patients with RA, Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut, and colleagues retrospectively evaluated US claims data from Optum’s Clinformatics Data Mart. The study population consisted of 381,221 patients aged 18 years and older who were diagnosed with AD from March 2017 to March 2023. Comparator groups included 381,221 non-AD controls matched by age, sex, and cohort entry, and 97,445 patients diagnosed with RA based on at least two claims for RA ≥ 7 days apart.
Patients were classified as having moderate to severe disease if they received dupilumab for AD or advanced systemic therapy for RA at any time during the follow-up period. The matched moderate to severe AD and non-AD cohorts were composed of 7134 patients each. The incidence of MACE was defined as inpatient hospitalization with myocardial infarction or stroke. The researchers used multivariable Cox proportional hazard models adjusted for baseline demographics, comorbidities, and medications to calculate the relative risk for MACE.
MACE Incidence, Relative Risk
The mean age of the AD cohort and non-AD matched controls was 58 years, and the mean age of the RA cohort was 67 years. The incidence of MACE per 100 patient-years was 1.78 among patients with AD, 1.83 among non-AD matched controls, and 2.12 among patients with RA. Patients with moderate to severe AD had a MACE incidence of 1.18 per 100 patient-years, which was lower than that of non-AD matched controls (1.52) and patients with moderate to severe RA (1.67).
In other findings, the relative risk for MACE in patients with AD was lower vs non-AD controls (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.89-0.93; P < .001) and patients with RA (aHR, 0.83; 95% CI, 0.80-0.85; P < .001). Among patients with moderate to severe AD, MACE risk was similar to that of non-AD matched controls (aHR, 0.92; 95% CI, 0.73-1.14) and lower vs those with moderate to severe RA (aHR, 0.83; 95% CI, 0.73-0.94; P < .01).
MACE risk associated with AD was greater in patients who were older (per year, aHR, 1.05; 95% CI, 1.05-1.05), male (aHR, 0.81; 95% CI, 0.79-0.84), and Black vs White (aHR, 1.16; 95% CI, 1.11-1.21), and among those who received systemic corticosteroids in the 3 months before diagnosis (aHR, 1.10; 95% CI, 1.06-1.14), were hospitalized in the year before diagnosis (aHR, 1.35; 95% CI, 1.30-1.41), and had a history of smoking (aHR, 1.20; 95% CI, 1.16-1.24) and drug abuse (aHR, 1.34; 95% CI, 1.25-1.43).
Unexpected Results
“One surprising finding was that the incidence of MACE in patients with moderate to severe AD was actually lower than that in non-AD matched controls and significantly lower compared to patients with moderate to severe RA,” Dr. Bunick said. “This contrasts with the expectation that increased systemic inflammation in moderate to severe AD would correspond with a higher incidence of MACE.”
Another unexpected result, he said, was that, among patients with moderate to severe AD, the risk for MACE was not significantly different from that of non-AD matched controls, suggesting that the inflammatory burden in AD might not translate to as high a cardiovascular risk as previously assumed.
Dr. Bunick noted that advanced treatments for AD such as Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) have a class boxed warning for MACE based on a study of another JAK inhibitor (tofacitinib) in patients with RA, but “this may not apply to AD because patients with AD have a lower risk for MACE.”
In his opinion, he said, the study “underscores the importance of understanding the specific risks associated with different inflammatory conditions.” Moreover, “it emphasizes the potential benefits of newer systemic therapies in potentially mitigating cardiovascular risks in patients with moderate to severe AD.”
Dr. Bunick acknowledged certain limitations of the study, including its retrospective design and reliance on administrative claims data, which “may introduce coding errors and misclassification,” and the generalizability of the results, which may be limited to the US population.
AbbVie funded the study, and three of the coauthors are employees of the company. Dr. Bunick disclosed that he has served as an investigator and/or a consultant for AbbVie, Almirall, Apogee, Arcutis Biotherapeutics, Connect Biopharma, Daiichi Sankyo, EPI Health/Novan, LEO, Lilly, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer, Sanofi Regeneron, Sun, Takeda, Timber, and UCB.
A version of this article appeared on Medscape.com.
Atopic Dermatitis: Study Compares Prevalence by Gender, Age, and Ethnic Background
than adults from other ethnic backgrounds.
Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.
“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.
“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”
Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.
More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.
In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.
When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.
On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).
“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”
Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”
In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”
Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.
A version of this article appeared on Medscape.com .
than adults from other ethnic backgrounds.
Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.
“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.
“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”
Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.
More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.
In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.
When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.
On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).
“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”
Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”
In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”
Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.
A version of this article appeared on Medscape.com .
than adults from other ethnic backgrounds.
Those are among the key findings from an analysis of nationally representative cross-sectional data that were presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis conference in Chicago.
“In the past few years, there has been a much-needed focus on better understanding disparities in atopic dermatitis,” one of the study authors, Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University, North Chicago, told this news organization after the conference.
“Epidemiology is one of the key ways in which we can query differences in AD at a population level.”
Drawing from the 2021 National Health Interview Survey, the researchers identified 3103 respondents who reported being diagnosed with AD or eczema. They estimated the prevalence rates of AD for the overall population and each subgroup by dividing US frequency estimates by their corresponding US population totals and used multivariable logistic regression to assess the odds of having AD.
More than half of the respondents (1643) were aged between 18 and 64 years, 522 were aged 65 years and older, and 922 were children younger than 18 years. Overall, the prevalence of AD was 7.6% in adults aged 18-64 years and 6.1% in adults aged 65 years and older, for a weighted US estimate of 15.3 and 3.2 million, respectively. The prevalence of AD varied by race/ethnicity and was highest for those from “other single and multiple races” group (12.4%), followed by Black/African American (8.5%), White (7.7%), Asian (6.5%), American Indian/Alaskan Native (4.9%), and Hispanic (4.8%) populations.
In children, race/ethnicity prevalence were highest for those from other single and multiple races (15.2.%), followed by Black/African American (14.2%), American Indian/Alaskan Native (12%), White (10.2%), Hispanic (9.5%), and Asian (9%) populations.
When the researchers combined all age groups, they observed higher prevalence rates of AD among females than among males. However, in an analysis limited to children, the prevalence rates were similar between girls and boys (10.8% vs 10.7%, respectively), for a weighted US estimate of 7.8 million children with AD.
On multiple regression, the odds of having AD were greater among women than among men (odds ratio [OR], 1.4), among adults aged 18-64 years than among those aged 65 years and older (OR, 1.4), among those younger than 18 years than among those aged 65 years and older (OR, 2.0), and among Black/African American individuals than among White individuals (OR, 1.2). Hispanic adults had a lower risk for AD than non-Hispanic White adults (OR, 0.69) as did Asian adults than White adults (OR, 0.82).
“We found AD prevalence rates were higher in children and adult females, Hispanic adults had a lower prevalence of AD than all other adult groups, and there were numerical differences in AD prevalence across racial groups,” Dr. Chovatiya said in the interview. “While there are of course limitations to the use of any nationally representative cross-sectional dataset that requires weighting to project results from a smaller sample to reflect a larger more heterogeneous group, these results are important for us to consider targeted strategies to address AD burden.”
Jonathan I. Silverberg, MD, PhD, professor of dermatology at The George Washington University, Washington, who was asked to comment on the study, said that while the prevalence of AD in children has been well documented in prior research, “this study fills an important gap by showing us that the prevalence does remain high in adults.”
In addition, “it has not shown any evidence of AD decreasing over time; if anything, it might be slightly increasing,” he said. “We’re also seeing differences [in AD] by race and ethnicity. We have seen that demonstrated in children but [has been] less clearly demonstrated in adults.”
Eli Lilly and Company funded the analysis. Dr. Chovatiya and Dr. Silverberg disclosed ties to several pharmaceutical companies, including Eli Lilly.
A version of this article appeared on Medscape.com .
Topical Ruxolitinib Effective for AD in Study of Children Ages 2-11 years
) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.
When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.
A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.
For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.
Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.
No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”
In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.
Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.
The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.
A version of this article appeared on Medscape.com.
) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.
When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.
A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.
For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.
Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.
No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”
In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.
Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.
The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.
A version of this article appeared on Medscape.com.
) affecting ≥ 35% or more of their body surface area (BSA), results from a small open-label maximum-use trial showed.
When approved for this age group, ruxolitinib cream will provide a topical nonsteroidal option for patients aged 2-11, which will “simplify the treatment regimen,” one of the study investigators, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session.
A topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor, ruxolitinib cream 1.5% is currently approved by the Food and Drug Administration for the short-term and noncontinuous chronic treatment of mild to moderate AD in non-immunocompromised adult and pediatric patients aged 12 years and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
In previous reports of this trial in children aged 2-11 years with ≥ 35% affected BSA, ruxolitinib cream 1.5% was generally well tolerated, with rapid anti-inflammatory and antipruritic effects and improvements in patient-reported outcomes observed with ≤ 4 weeks of continuous treatment and maintained with as-needed treatment from 4 to 8 weeks.
For the current trial, investigators evaluated data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes through 52 weeks to determine whether clinical benefits and tolerability observed through 8 weeks were sustained.
Dr. Stein Gold and colleagues reported results from 29 children who received ruxolitinib cream 1.5% from baseline through week 8. Of these, 22 continued into the long-term safety period from week 8 through 52. From baseline through week 8, patients applied a mean of 6.5 g per day of ruxolitinib cream; this dropped to a mean of 3.2 g per day from weeks 8 through 52. The mean steady-state plasma concentration of ruxolitinib throughout the study was 98.2 nM, which is “well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM),” the researchers stated in their abstract.
No treatment-related interruptions, discontinuations, or serious adverse events were observed between baseline and week 52. One patient (3.4%) had two treatment-related application site reactions (paresthesia and folliculitis). At weeks 4 and 52, 53.8% of patients achieved treatment success, which was defined as an Investigator Global Assessment of 0/1 with a ≥ 2-grade improvement from baseline. The mean affected BSA decreased from 58.0% at baseline to 11.4% at week 4 and continued to decrease to 2.2% through week 52. “I was surprised that patients could maintain control over the long-term using the medication as needed,” Dr. Stein Gold told this news organization. “I was also pleased to see that there was low systemic exposure even when used on large body surface areas.”
In other findings, the mean total Patient Oriented Eczema Measure score dropped from a baseline of 19.4 to a mean of 4.5 at week 8 and 3.6 at week 52 and the mean total Children’s Dermatology Life Quality Index score fell from a baseline of 15.4 to a mean of 5.3 at week 8 and a mean of 2.1 at week 52. Meanwhile, the mean total Infants’ Dermatology Quality of Life Index score fell from a mean of 12.3 at baseline to a mean of 2.8 at week 8 and a mean of 0.7 at week 52.
Dr. Stein Gold noted certain limitations of the study, including the fact that it did not study children aged younger than 2 years.
The study was funded by Incyte, which markets ruxolitinib cream 1.5% as Opzelura. Dr. Stein Gold disclosed that she has served as an investigator, advisor, and/or speaker for several pharmaceutical companies, including Incyte.
A version of this article appeared on Medscape.com.