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FDA OKs low-dose colchicine for broad CV indication
The Food and Drug Administration has approved the anti-inflammatory drug colchicine 0.5 mg tablets (Lodoco) as the first specific anti-inflammatory drug demonstrated to reduce the risk for myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.
The drug, which targets residual inflammation as an underlying cause of atherosclerotic cardiovascular disease, has a dosage of 0.5 mg once daily, and can be used alone or in combination with cholesterol-lowering medications. 
The drug’s manufacturer, Agepha Pharma, said it anticipates that Lodoco will be available for prescription in the second half of 2023.
Colchicine has been available for many years and used at higher doses for the acute treatment of gout and pericarditis, but the current formulation is a much lower dose for long-term use in patients with atherosclerotic heart disease.
Data supporting the approval has come from two major randomized trials, LoDoCo-2 and COLCOT.
In the LoDoCo-2 trial, the anti-inflammatory drug cut the risk of cardiovascular events by one third when added to standard prevention therapies in patients with chronic coronary disease. And in the COLCOT study, use of colchicine reduced cardiovascular events by 23% compared with placebo in patients with a recent MI.
Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, who has been a pioneer in establishing inflammation as an underlying cause of atherosclerotic cardiovascular disease, welcomed the Lodoco approval.
‘A very big day for cardiology’
“This is a very big day for cardiology,” Dr. Ridker said in an interview.
“The FDA approval of colchicine for patients with atherosclerotic disease is a huge signal that physicians need to be aware of inflammation as a key player in cardiovascular disease,” he said.
Dr. Ridker was the lead author of a recent study showing that among patients receiving contemporary statins, inflammation assessed by high-sensitivity C-reactive protein (hsCRP) was a stronger predictor for risk of future cardiovascular events and death than LDL cholesterol.
He pointed out that
“That is virtually identical to the indication approved for statin therapy. That shows just how important the FDA thinks this is,” he commented.
But Dr. Ridker added that, while the label does not specify that Lodoco has to be used in addition to statin therapy, he believes that it will be used as additional therapy to statins in the vast majority of patients.
“This is not an alternative to statin therapy. In the randomized trials, the benefits were seen on top of statins,” he stressed.
Dr. Ridker believes that physicians will need time to feel comfortable with this new approach.
“Initially, I think, it will be used mainly by cardiologists who know about inflammation, but I believe over time it will be widely prescribed by internists, in much the same way as statins are used today,” he commented.
Dr. Ridker said he already uses low dose colchicine in his high-risk patients who have high levels of inflammation as seen on hsCRP testing. He believes this is where the drug will mostly be used initially, as this is where it is likely to be most effective.
The prescribing information states that Lodoco is contraindicated in patients who are taking strong CYP3A4 inhibitors or P-glycoprotein inhibitors, such as ketoconazole, fluconazole, and clarithromycin, and in patients with preexisting blood dyscrasias, renal failure, and severe hepatic impairment.
Common side effects reported in published clinical studies and literature with the use of colchicine are gastrointestinal symptoms (diarrhea, vomiting, abdominal cramping) and myalgia.
More serious adverse effects are listed as blood dyscrasias such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia; and neuromuscular toxicity in the form of myotoxicity including rhabdomyolysis, which may occur, especially in combination with other drugs known to cause this effect. If these adverse effects occur, it is recommended that the drug be stopped.
The prescribing information also notes that Lodoco may rarely and transiently impair fertility in males; and that patients with renal or hepatic impairment should be monitored closely for adverse effects of colchicine.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the anti-inflammatory drug colchicine 0.5 mg tablets (Lodoco) as the first specific anti-inflammatory drug demonstrated to reduce the risk for myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.
The drug, which targets residual inflammation as an underlying cause of atherosclerotic cardiovascular disease, has a dosage of 0.5 mg once daily, and can be used alone or in combination with cholesterol-lowering medications.
The drug’s manufacturer, Agepha Pharma, said it anticipates that Lodoco will be available for prescription in the second half of 2023.
Colchicine has been available for many years and used at higher doses for the acute treatment of gout and pericarditis, but the current formulation is a much lower dose for long-term use in patients with atherosclerotic heart disease.
Data supporting the approval has come from two major randomized trials, LoDoCo-2 and COLCOT.
In the LoDoCo-2 trial, the anti-inflammatory drug cut the risk of cardiovascular events by one third when added to standard prevention therapies in patients with chronic coronary disease. And in the COLCOT study, use of colchicine reduced cardiovascular events by 23% compared with placebo in patients with a recent MI.
Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, who has been a pioneer in establishing inflammation as an underlying cause of atherosclerotic cardiovascular disease, welcomed the Lodoco approval.
‘A very big day for cardiology’
“This is a very big day for cardiology,” Dr. Ridker said in an interview.
“The FDA approval of colchicine for patients with atherosclerotic disease is a huge signal that physicians need to be aware of inflammation as a key player in cardiovascular disease,” he said.
Dr. Ridker was the lead author of a recent study showing that among patients receiving contemporary statins, inflammation assessed by high-sensitivity C-reactive protein (hsCRP) was a stronger predictor for risk of future cardiovascular events and death than LDL cholesterol.
He pointed out that
“That is virtually identical to the indication approved for statin therapy. That shows just how important the FDA thinks this is,” he commented.
But Dr. Ridker added that, while the label does not specify that Lodoco has to be used in addition to statin therapy, he believes that it will be used as additional therapy to statins in the vast majority of patients.
“This is not an alternative to statin therapy. In the randomized trials, the benefits were seen on top of statins,” he stressed.
Dr. Ridker believes that physicians will need time to feel comfortable with this new approach.
“Initially, I think, it will be used mainly by cardiologists who know about inflammation, but I believe over time it will be widely prescribed by internists, in much the same way as statins are used today,” he commented.
Dr. Ridker said he already uses low dose colchicine in his high-risk patients who have high levels of inflammation as seen on hsCRP testing. He believes this is where the drug will mostly be used initially, as this is where it is likely to be most effective.
The prescribing information states that Lodoco is contraindicated in patients who are taking strong CYP3A4 inhibitors or P-glycoprotein inhibitors, such as ketoconazole, fluconazole, and clarithromycin, and in patients with preexisting blood dyscrasias, renal failure, and severe hepatic impairment.
Common side effects reported in published clinical studies and literature with the use of colchicine are gastrointestinal symptoms (diarrhea, vomiting, abdominal cramping) and myalgia.
More serious adverse effects are listed as blood dyscrasias such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia; and neuromuscular toxicity in the form of myotoxicity including rhabdomyolysis, which may occur, especially in combination with other drugs known to cause this effect. If these adverse effects occur, it is recommended that the drug be stopped.
The prescribing information also notes that Lodoco may rarely and transiently impair fertility in males; and that patients with renal or hepatic impairment should be monitored closely for adverse effects of colchicine.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the anti-inflammatory drug colchicine 0.5 mg tablets (Lodoco) as the first specific anti-inflammatory drug demonstrated to reduce the risk for myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.
The drug, which targets residual inflammation as an underlying cause of atherosclerotic cardiovascular disease, has a dosage of 0.5 mg once daily, and can be used alone or in combination with cholesterol-lowering medications.
The drug’s manufacturer, Agepha Pharma, said it anticipates that Lodoco will be available for prescription in the second half of 2023.
Colchicine has been available for many years and used at higher doses for the acute treatment of gout and pericarditis, but the current formulation is a much lower dose for long-term use in patients with atherosclerotic heart disease.
Data supporting the approval has come from two major randomized trials, LoDoCo-2 and COLCOT.
In the LoDoCo-2 trial, the anti-inflammatory drug cut the risk of cardiovascular events by one third when added to standard prevention therapies in patients with chronic coronary disease. And in the COLCOT study, use of colchicine reduced cardiovascular events by 23% compared with placebo in patients with a recent MI.
Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, who has been a pioneer in establishing inflammation as an underlying cause of atherosclerotic cardiovascular disease, welcomed the Lodoco approval.
‘A very big day for cardiology’
“This is a very big day for cardiology,” Dr. Ridker said in an interview.
“The FDA approval of colchicine for patients with atherosclerotic disease is a huge signal that physicians need to be aware of inflammation as a key player in cardiovascular disease,” he said.
Dr. Ridker was the lead author of a recent study showing that among patients receiving contemporary statins, inflammation assessed by high-sensitivity C-reactive protein (hsCRP) was a stronger predictor for risk of future cardiovascular events and death than LDL cholesterol.
He pointed out that
“That is virtually identical to the indication approved for statin therapy. That shows just how important the FDA thinks this is,” he commented.
But Dr. Ridker added that, while the label does not specify that Lodoco has to be used in addition to statin therapy, he believes that it will be used as additional therapy to statins in the vast majority of patients.
“This is not an alternative to statin therapy. In the randomized trials, the benefits were seen on top of statins,” he stressed.
Dr. Ridker believes that physicians will need time to feel comfortable with this new approach.
“Initially, I think, it will be used mainly by cardiologists who know about inflammation, but I believe over time it will be widely prescribed by internists, in much the same way as statins are used today,” he commented.
Dr. Ridker said he already uses low dose colchicine in his high-risk patients who have high levels of inflammation as seen on hsCRP testing. He believes this is where the drug will mostly be used initially, as this is where it is likely to be most effective.
The prescribing information states that Lodoco is contraindicated in patients who are taking strong CYP3A4 inhibitors or P-glycoprotein inhibitors, such as ketoconazole, fluconazole, and clarithromycin, and in patients with preexisting blood dyscrasias, renal failure, and severe hepatic impairment.
Common side effects reported in published clinical studies and literature with the use of colchicine are gastrointestinal symptoms (diarrhea, vomiting, abdominal cramping) and myalgia.
More serious adverse effects are listed as blood dyscrasias such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia; and neuromuscular toxicity in the form of myotoxicity including rhabdomyolysis, which may occur, especially in combination with other drugs known to cause this effect. If these adverse effects occur, it is recommended that the drug be stopped.
The prescribing information also notes that Lodoco may rarely and transiently impair fertility in males; and that patients with renal or hepatic impairment should be monitored closely for adverse effects of colchicine.
A version of this article first appeared on Medscape.com.
Aspirin warning: Anemia may increase with daily use
, according to results from a new randomized controlled trial.
In the study, which was published in Annals of Internal Medicine, investigators analyzed data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial and examined hemoglobin concentrations among 19,114 healthy, community-dwelling older patients.
“We knew from large clinical trials, including our ASPREE trial, that daily low-dose aspirin increased the risk of clinically significant bleeding,” said Zoe McQuilten, MBBS, PhD, a hematologist at Monash University in Australia and the study’s lead author. “From our study, we found that low-dose aspirin also increased the risk of anemia during the trial, and this was most likely due to bleeding that was not clinically apparent.”
Anemia is common among elderly patients. It can cause fatigue, fast or irregular heartbeat, headache, chest pain, and pounding or whooshing sounds in the ear, according to the Cleveland Clinic. It can also worsen conditions such as heart failure, cognitive impairment, and depression in people aged 65 and older.
The U.S. Preventive Services Task Force changed its recommendation on aspirin for the primary prevention of cardiovascular disease in 2022, recommending against initiating low-dose aspirin for adults aged 60 years or older. For adults aged 40-59 who have a 10% or greater 10-year risk for cardiovascular disease, the agency recommends that patients and clinicians make the decision to initiate low-dose aspirin use on a case-by-case basis, as the net benefit is small.
Dr. McQuilten said she spent the last 5 years designing substages of anemia and conditions such as blood cancer. In many cases of anemia, doctors are unable to determine the underlying cause, she said. One study published in the Journal of American Geriatrics Society in 2021 found that in about one-third of anemia cases, the etiology was not clear.
About 50% of people older than 60 who were involved in the latest study took aspirin for prevention from 2011 to 2018. That number likely dropped after changes were made to the guidelines in 2022, according to Dr. McQuilten, but long-term use may have continued among older patients. The researchers also examined ferritin levels, which serve as a proxy for iron levels, at baseline and after 3 years.
The incidence of anemia was 51 events per 1,000 person-years in the aspirin group compared with 43 events per 1,000 person-years in the placebo group, according to the researchers. The estimated probability of experiencing anemia within 5 years was 23.5% (95% confidence interval [CI], 22.4%-24.6%) in the aspirin group and 20.3% (95% CI: 19.3% to 21.4%) in the placebo group. Aspirin therapy resulted in a 20% increase in the risk for anemia (95% CI, 1.12-1.29).
People who took aspirin were more likely to have lower serum levels of ferritin at the 3-year mark than were those who received placebo. The average decrease in ferritin among participants who took aspirin was 11.5% greater (95% CI, 9.3%-13.7%) than among those who took placebo.
Basil Eldadah, MD, PhD, supervisory medical officer at the National Institute on Aging, part of the National Institutes of Health, said the findings should encourage clinicians to pay closer attention to hemoglobin levels and have conversations with patients to discuss their need for taking aspirin.
“If somebody is already taking aspirin for any reason, keep an eye on hemoglobin,” said Dr. Eldadah, who was not involved in the study. “For somebody who’s taking aspirin and who’s older, and it’s not for an indication like cardiovascular disease, consider seriously whether that’s the best treatment option.”
The study did not examine the functional consequences of anemia on participants, which Dr. Eldadah said could be fodder for future research. The researchers said one limitation was that it was not clear whether anemia was sufficient to cause symptoms that affected participants’ quality of life or whether occult bleeding caused the anemia. The researchers also did not document whether patients saw their regular physicians and received treatment for anemia over the course of the trial.
The study was funded through grants from the National Health and Medical Research Council and the Bill and Melinda Gates Foundation. The authors reported receiving consulting fees, honoraria, and stock options, and have participated on data monitoring boards not related to the study for Vifor Pharma, ITL Biomedical, Pfizer, Boehringer Ingelheim, Bayer Healthcare, AbbVie, and Abbott Diagnostics.
A version of this article originally appeared on Medscape.com.
, according to results from a new randomized controlled trial.
In the study, which was published in Annals of Internal Medicine, investigators analyzed data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial and examined hemoglobin concentrations among 19,114 healthy, community-dwelling older patients.
“We knew from large clinical trials, including our ASPREE trial, that daily low-dose aspirin increased the risk of clinically significant bleeding,” said Zoe McQuilten, MBBS, PhD, a hematologist at Monash University in Australia and the study’s lead author. “From our study, we found that low-dose aspirin also increased the risk of anemia during the trial, and this was most likely due to bleeding that was not clinically apparent.”
Anemia is common among elderly patients. It can cause fatigue, fast or irregular heartbeat, headache, chest pain, and pounding or whooshing sounds in the ear, according to the Cleveland Clinic. It can also worsen conditions such as heart failure, cognitive impairment, and depression in people aged 65 and older.
The U.S. Preventive Services Task Force changed its recommendation on aspirin for the primary prevention of cardiovascular disease in 2022, recommending against initiating low-dose aspirin for adults aged 60 years or older. For adults aged 40-59 who have a 10% or greater 10-year risk for cardiovascular disease, the agency recommends that patients and clinicians make the decision to initiate low-dose aspirin use on a case-by-case basis, as the net benefit is small.
Dr. McQuilten said she spent the last 5 years designing substages of anemia and conditions such as blood cancer. In many cases of anemia, doctors are unable to determine the underlying cause, she said. One study published in the Journal of American Geriatrics Society in 2021 found that in about one-third of anemia cases, the etiology was not clear.
About 50% of people older than 60 who were involved in the latest study took aspirin for prevention from 2011 to 2018. That number likely dropped after changes were made to the guidelines in 2022, according to Dr. McQuilten, but long-term use may have continued among older patients. The researchers also examined ferritin levels, which serve as a proxy for iron levels, at baseline and after 3 years.
The incidence of anemia was 51 events per 1,000 person-years in the aspirin group compared with 43 events per 1,000 person-years in the placebo group, according to the researchers. The estimated probability of experiencing anemia within 5 years was 23.5% (95% confidence interval [CI], 22.4%-24.6%) in the aspirin group and 20.3% (95% CI: 19.3% to 21.4%) in the placebo group. Aspirin therapy resulted in a 20% increase in the risk for anemia (95% CI, 1.12-1.29).
People who took aspirin were more likely to have lower serum levels of ferritin at the 3-year mark than were those who received placebo. The average decrease in ferritin among participants who took aspirin was 11.5% greater (95% CI, 9.3%-13.7%) than among those who took placebo.
Basil Eldadah, MD, PhD, supervisory medical officer at the National Institute on Aging, part of the National Institutes of Health, said the findings should encourage clinicians to pay closer attention to hemoglobin levels and have conversations with patients to discuss their need for taking aspirin.
“If somebody is already taking aspirin for any reason, keep an eye on hemoglobin,” said Dr. Eldadah, who was not involved in the study. “For somebody who’s taking aspirin and who’s older, and it’s not for an indication like cardiovascular disease, consider seriously whether that’s the best treatment option.”
The study did not examine the functional consequences of anemia on participants, which Dr. Eldadah said could be fodder for future research. The researchers said one limitation was that it was not clear whether anemia was sufficient to cause symptoms that affected participants’ quality of life or whether occult bleeding caused the anemia. The researchers also did not document whether patients saw their regular physicians and received treatment for anemia over the course of the trial.
The study was funded through grants from the National Health and Medical Research Council and the Bill and Melinda Gates Foundation. The authors reported receiving consulting fees, honoraria, and stock options, and have participated on data monitoring boards not related to the study for Vifor Pharma, ITL Biomedical, Pfizer, Boehringer Ingelheim, Bayer Healthcare, AbbVie, and Abbott Diagnostics.
A version of this article originally appeared on Medscape.com.
, according to results from a new randomized controlled trial.
In the study, which was published in Annals of Internal Medicine, investigators analyzed data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial and examined hemoglobin concentrations among 19,114 healthy, community-dwelling older patients.
“We knew from large clinical trials, including our ASPREE trial, that daily low-dose aspirin increased the risk of clinically significant bleeding,” said Zoe McQuilten, MBBS, PhD, a hematologist at Monash University in Australia and the study’s lead author. “From our study, we found that low-dose aspirin also increased the risk of anemia during the trial, and this was most likely due to bleeding that was not clinically apparent.”
Anemia is common among elderly patients. It can cause fatigue, fast or irregular heartbeat, headache, chest pain, and pounding or whooshing sounds in the ear, according to the Cleveland Clinic. It can also worsen conditions such as heart failure, cognitive impairment, and depression in people aged 65 and older.
The U.S. Preventive Services Task Force changed its recommendation on aspirin for the primary prevention of cardiovascular disease in 2022, recommending against initiating low-dose aspirin for adults aged 60 years or older. For adults aged 40-59 who have a 10% or greater 10-year risk for cardiovascular disease, the agency recommends that patients and clinicians make the decision to initiate low-dose aspirin use on a case-by-case basis, as the net benefit is small.
Dr. McQuilten said she spent the last 5 years designing substages of anemia and conditions such as blood cancer. In many cases of anemia, doctors are unable to determine the underlying cause, she said. One study published in the Journal of American Geriatrics Society in 2021 found that in about one-third of anemia cases, the etiology was not clear.
About 50% of people older than 60 who were involved in the latest study took aspirin for prevention from 2011 to 2018. That number likely dropped after changes were made to the guidelines in 2022, according to Dr. McQuilten, but long-term use may have continued among older patients. The researchers also examined ferritin levels, which serve as a proxy for iron levels, at baseline and after 3 years.
The incidence of anemia was 51 events per 1,000 person-years in the aspirin group compared with 43 events per 1,000 person-years in the placebo group, according to the researchers. The estimated probability of experiencing anemia within 5 years was 23.5% (95% confidence interval [CI], 22.4%-24.6%) in the aspirin group and 20.3% (95% CI: 19.3% to 21.4%) in the placebo group. Aspirin therapy resulted in a 20% increase in the risk for anemia (95% CI, 1.12-1.29).
People who took aspirin were more likely to have lower serum levels of ferritin at the 3-year mark than were those who received placebo. The average decrease in ferritin among participants who took aspirin was 11.5% greater (95% CI, 9.3%-13.7%) than among those who took placebo.
Basil Eldadah, MD, PhD, supervisory medical officer at the National Institute on Aging, part of the National Institutes of Health, said the findings should encourage clinicians to pay closer attention to hemoglobin levels and have conversations with patients to discuss their need for taking aspirin.
“If somebody is already taking aspirin for any reason, keep an eye on hemoglobin,” said Dr. Eldadah, who was not involved in the study. “For somebody who’s taking aspirin and who’s older, and it’s not for an indication like cardiovascular disease, consider seriously whether that’s the best treatment option.”
The study did not examine the functional consequences of anemia on participants, which Dr. Eldadah said could be fodder for future research. The researchers said one limitation was that it was not clear whether anemia was sufficient to cause symptoms that affected participants’ quality of life or whether occult bleeding caused the anemia. The researchers also did not document whether patients saw their regular physicians and received treatment for anemia over the course of the trial.
The study was funded through grants from the National Health and Medical Research Council and the Bill and Melinda Gates Foundation. The authors reported receiving consulting fees, honoraria, and stock options, and have participated on data monitoring boards not related to the study for Vifor Pharma, ITL Biomedical, Pfizer, Boehringer Ingelheim, Bayer Healthcare, AbbVie, and Abbott Diagnostics.
A version of this article originally appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Combo treatment eases nausea and vomiting of pregnancy
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
FROM ANNALS OF INTERNAL MEDICINE
‘Deprescribing’: Should some older adults shed their meds?
Joanne Lynn, MD, has lost track of the number of times in her 40 years as a geriatrician she’s seen a new patient come to her office carrying a bucket full of prescription medications – many of which they don’t need.
Dr. Lynn, who is on the faculty of George Washington University,Washington, recalled one woman who unwittingly was taking two blood pressure medications with different names.
“The risks included all the side effects overdosing carries,” Dr. Lynn said, ranging from blurred vision and crankiness to organ failure and even death.
For doctors with patients who don’t know they’re taking too much of a medication, “you wonder whether the drug is causing the health problems, and it’s a symptom of the wrong medication,” rather than a symptom of an undiagnosed illness, she said.
Patients often assume their health providers check for drug interactions or assess if a medication is no longer needed, and will catch extra prescriptions. That could be a risky assumption. Some doctors may prescribe yet another prescription to manage the side effects of an unnecessary drug, instead of doing a medication review and potentially “deprescribing” or discontinuing, a treatment that’s no longer needed.
About 57% of people age 65 years or older take five or more medications regularly – a concept known as polypharmacy, a study published in 2020 in the Journal of the American Geriatrics Society shows. While doctors prescribe drugs to help patients manage various ailments, as a list of medications grows, so do potential complications.
An older adult might forget to tell their doctor what they’re taking, or maybe they don’t even know what they’re taking or why, Dr. Lynn said.
“In some cases, a doctor just added a drug to treat something, not realizing they were already taking something else for it,” she said. “Of course, the situation of whether these patients can even afford all these drugs matters a lot, too.”
Some older adults may pick and choose which medications to take based on cost, not knowing which prescriptions are necessary, Dr. Lynn said.
Finding the ‘right balance’
Indeed, if given the option, up to 80% of older adults ages 50-80 would be open to stopping one or more of their prescribed medications, according to a 2023 poll by researchers at the University of Michigan, Ann Arbor.
“A lot of drugs that people take might have been appropriate at one point, but might have outlived their usefulness for that individual,” said Michael Steinman, MD, a professor of medicine and a geriatrician at the University of California, San Francisco, and coprincipal investigator of the U.S. Deprescribing Research Network, a doctor group focused on improving medication use for older adults.
“Having fewer medications can actually be beneficial,” he said. “You can take too many medications; you can take too few. The optimal thing is finding what is the right balance for you.”
Defining how many medications is too many depends on each person, which is why caregivers and older adults can ask their doctor for a review of medications that have multiplied over time.
By reevaluating their medications, older adults can actually lower their chances of potentially harmful side effects, and avoid the spiral of being prescribed even more medications, said Sarah Vordenberg, PharmD, MPH, a clinical associate professor at the University of Michigan’s College of Pharmacy, Ann Arbor.
“It’s not really the number of medications, it’s [about] are they inappropriate or unnecessary medications for a patient,” she said.
Patients and caregivers can ask for an honest conversation with their doctor. The University of Michigan poll found that more than 90% of older adults who took prescription medications expected their health care provider to review their medicines during a regular visit.
But doctors often need prompting from patients to start a review.
“The clinical inertia, or maintaining the status quo, unfortunately is a lot of times easier than having time-intensive conversations,” Dr. Vordenberg said.
Ask questions
Sara Merwin spent many years helping manage her parents’ medical appointments and health as they transitioned from living independently in Colorado to a retirement community and finally a nursing home. Ms. Merwin, coauthor of “The Informed Patient,” said her father was taking a long list of medications, and she often asked his primary care doctor for a medication review.
“I felt that my father at his age and his frailty didn’t need as many meds as he was on,” said Ms. Merwin, who lives in Long Island, N.Y. “So we went over his meds, and I asked, ‘Does he really need to be on this?’ ‘Does he really need to be on that?’ ”
She questioned one medication in particular, a statin to lower his cholesterol and risk of a heart attack.
“I thought possibly the statin was causing some myalgia, some muscle aches in his legs, which is why I advocated for coming off it,” she said.
The primary care doctor discontinued the anticholesterol drug.
Local pharmacies can also serve as a starting point for older adults and caregivers, where a pharmacist can give them more information on whether a particular combination of the medications taken may be harmful. In states that allow for pharmacists to prescribe some medications, pharmacists may be able to consolidate some of the medications or advise that a patient stop taking one or more, Dr. Vordenberg said.
“All pharmacists have the training to do a comprehensive medication review,” she said. “All pharmacists have the ability to follow up with the patient to find out how the deprescribing is going.”
Ms. Merwin’s parents received their prescriptions from a “small mom-and-pop pharmacy, where they were on a first-name basis with the pharmacist who really looked out for them. So they had that expertise available to them,” she said.
With information in hand on potentially unnecessary medications, the work of shedding medications should be done along with health care providers, some of whom prescribed the medications in the first place.
Many older adults live in geographically isolated areas without pharmacies, or receive prescriptions from mail-order pharmacies. In this case, Medicare plans offer free medication reviews with a doctor or pharmacist – known as a medication therapy management program – and provide recommendations for taking each drug.
Ms. Merwin’s father died in early 2020. She sometimes questions whether he should have stayed on the statin for longer, or if the doctor agreed too quickly without doing more research. But overall, she doesn’t regret raising the question with his health care providers, and she advises other caregivers and older adults to pay attention to medication lists.
“It’s dangerous to be passive when it comes to one’s health care now,” Ms. Merwin said. “That’s a difficult message for older adults to hear because they have grown up with the primacy of the doctor and the authority of the doctor, as opposed to it being a collaborative relationship.”
A version of this article first appeared on WebMD.com.
Joanne Lynn, MD, has lost track of the number of times in her 40 years as a geriatrician she’s seen a new patient come to her office carrying a bucket full of prescription medications – many of which they don’t need.
Dr. Lynn, who is on the faculty of George Washington University,Washington, recalled one woman who unwittingly was taking two blood pressure medications with different names.
“The risks included all the side effects overdosing carries,” Dr. Lynn said, ranging from blurred vision and crankiness to organ failure and even death.
For doctors with patients who don’t know they’re taking too much of a medication, “you wonder whether the drug is causing the health problems, and it’s a symptom of the wrong medication,” rather than a symptom of an undiagnosed illness, she said.
Patients often assume their health providers check for drug interactions or assess if a medication is no longer needed, and will catch extra prescriptions. That could be a risky assumption. Some doctors may prescribe yet another prescription to manage the side effects of an unnecessary drug, instead of doing a medication review and potentially “deprescribing” or discontinuing, a treatment that’s no longer needed.
About 57% of people age 65 years or older take five or more medications regularly – a concept known as polypharmacy, a study published in 2020 in the Journal of the American Geriatrics Society shows. While doctors prescribe drugs to help patients manage various ailments, as a list of medications grows, so do potential complications.
An older adult might forget to tell their doctor what they’re taking, or maybe they don’t even know what they’re taking or why, Dr. Lynn said.
“In some cases, a doctor just added a drug to treat something, not realizing they were already taking something else for it,” she said. “Of course, the situation of whether these patients can even afford all these drugs matters a lot, too.”
Some older adults may pick and choose which medications to take based on cost, not knowing which prescriptions are necessary, Dr. Lynn said.
Finding the ‘right balance’
Indeed, if given the option, up to 80% of older adults ages 50-80 would be open to stopping one or more of their prescribed medications, according to a 2023 poll by researchers at the University of Michigan, Ann Arbor.
“A lot of drugs that people take might have been appropriate at one point, but might have outlived their usefulness for that individual,” said Michael Steinman, MD, a professor of medicine and a geriatrician at the University of California, San Francisco, and coprincipal investigator of the U.S. Deprescribing Research Network, a doctor group focused on improving medication use for older adults.
“Having fewer medications can actually be beneficial,” he said. “You can take too many medications; you can take too few. The optimal thing is finding what is the right balance for you.”
Defining how many medications is too many depends on each person, which is why caregivers and older adults can ask their doctor for a review of medications that have multiplied over time.
By reevaluating their medications, older adults can actually lower their chances of potentially harmful side effects, and avoid the spiral of being prescribed even more medications, said Sarah Vordenberg, PharmD, MPH, a clinical associate professor at the University of Michigan’s College of Pharmacy, Ann Arbor.
“It’s not really the number of medications, it’s [about] are they inappropriate or unnecessary medications for a patient,” she said.
Patients and caregivers can ask for an honest conversation with their doctor. The University of Michigan poll found that more than 90% of older adults who took prescription medications expected their health care provider to review their medicines during a regular visit.
But doctors often need prompting from patients to start a review.
“The clinical inertia, or maintaining the status quo, unfortunately is a lot of times easier than having time-intensive conversations,” Dr. Vordenberg said.
Ask questions
Sara Merwin spent many years helping manage her parents’ medical appointments and health as they transitioned from living independently in Colorado to a retirement community and finally a nursing home. Ms. Merwin, coauthor of “The Informed Patient,” said her father was taking a long list of medications, and she often asked his primary care doctor for a medication review.
“I felt that my father at his age and his frailty didn’t need as many meds as he was on,” said Ms. Merwin, who lives in Long Island, N.Y. “So we went over his meds, and I asked, ‘Does he really need to be on this?’ ‘Does he really need to be on that?’ ”
She questioned one medication in particular, a statin to lower his cholesterol and risk of a heart attack.
“I thought possibly the statin was causing some myalgia, some muscle aches in his legs, which is why I advocated for coming off it,” she said.
The primary care doctor discontinued the anticholesterol drug.
Local pharmacies can also serve as a starting point for older adults and caregivers, where a pharmacist can give them more information on whether a particular combination of the medications taken may be harmful. In states that allow for pharmacists to prescribe some medications, pharmacists may be able to consolidate some of the medications or advise that a patient stop taking one or more, Dr. Vordenberg said.
“All pharmacists have the training to do a comprehensive medication review,” she said. “All pharmacists have the ability to follow up with the patient to find out how the deprescribing is going.”
Ms. Merwin’s parents received their prescriptions from a “small mom-and-pop pharmacy, where they were on a first-name basis with the pharmacist who really looked out for them. So they had that expertise available to them,” she said.
With information in hand on potentially unnecessary medications, the work of shedding medications should be done along with health care providers, some of whom prescribed the medications in the first place.
Many older adults live in geographically isolated areas without pharmacies, or receive prescriptions from mail-order pharmacies. In this case, Medicare plans offer free medication reviews with a doctor or pharmacist – known as a medication therapy management program – and provide recommendations for taking each drug.
Ms. Merwin’s father died in early 2020. She sometimes questions whether he should have stayed on the statin for longer, or if the doctor agreed too quickly without doing more research. But overall, she doesn’t regret raising the question with his health care providers, and she advises other caregivers and older adults to pay attention to medication lists.
“It’s dangerous to be passive when it comes to one’s health care now,” Ms. Merwin said. “That’s a difficult message for older adults to hear because they have grown up with the primacy of the doctor and the authority of the doctor, as opposed to it being a collaborative relationship.”
A version of this article first appeared on WebMD.com.
Joanne Lynn, MD, has lost track of the number of times in her 40 years as a geriatrician she’s seen a new patient come to her office carrying a bucket full of prescription medications – many of which they don’t need.
Dr. Lynn, who is on the faculty of George Washington University,Washington, recalled one woman who unwittingly was taking two blood pressure medications with different names.
“The risks included all the side effects overdosing carries,” Dr. Lynn said, ranging from blurred vision and crankiness to organ failure and even death.
For doctors with patients who don’t know they’re taking too much of a medication, “you wonder whether the drug is causing the health problems, and it’s a symptom of the wrong medication,” rather than a symptom of an undiagnosed illness, she said.
Patients often assume their health providers check for drug interactions or assess if a medication is no longer needed, and will catch extra prescriptions. That could be a risky assumption. Some doctors may prescribe yet another prescription to manage the side effects of an unnecessary drug, instead of doing a medication review and potentially “deprescribing” or discontinuing, a treatment that’s no longer needed.
About 57% of people age 65 years or older take five or more medications regularly – a concept known as polypharmacy, a study published in 2020 in the Journal of the American Geriatrics Society shows. While doctors prescribe drugs to help patients manage various ailments, as a list of medications grows, so do potential complications.
An older adult might forget to tell their doctor what they’re taking, or maybe they don’t even know what they’re taking or why, Dr. Lynn said.
“In some cases, a doctor just added a drug to treat something, not realizing they were already taking something else for it,” she said. “Of course, the situation of whether these patients can even afford all these drugs matters a lot, too.”
Some older adults may pick and choose which medications to take based on cost, not knowing which prescriptions are necessary, Dr. Lynn said.
Finding the ‘right balance’
Indeed, if given the option, up to 80% of older adults ages 50-80 would be open to stopping one or more of their prescribed medications, according to a 2023 poll by researchers at the University of Michigan, Ann Arbor.
“A lot of drugs that people take might have been appropriate at one point, but might have outlived their usefulness for that individual,” said Michael Steinman, MD, a professor of medicine and a geriatrician at the University of California, San Francisco, and coprincipal investigator of the U.S. Deprescribing Research Network, a doctor group focused on improving medication use for older adults.
“Having fewer medications can actually be beneficial,” he said. “You can take too many medications; you can take too few. The optimal thing is finding what is the right balance for you.”
Defining how many medications is too many depends on each person, which is why caregivers and older adults can ask their doctor for a review of medications that have multiplied over time.
By reevaluating their medications, older adults can actually lower their chances of potentially harmful side effects, and avoid the spiral of being prescribed even more medications, said Sarah Vordenberg, PharmD, MPH, a clinical associate professor at the University of Michigan’s College of Pharmacy, Ann Arbor.
“It’s not really the number of medications, it’s [about] are they inappropriate or unnecessary medications for a patient,” she said.
Patients and caregivers can ask for an honest conversation with their doctor. The University of Michigan poll found that more than 90% of older adults who took prescription medications expected their health care provider to review their medicines during a regular visit.
But doctors often need prompting from patients to start a review.
“The clinical inertia, or maintaining the status quo, unfortunately is a lot of times easier than having time-intensive conversations,” Dr. Vordenberg said.
Ask questions
Sara Merwin spent many years helping manage her parents’ medical appointments and health as they transitioned from living independently in Colorado to a retirement community and finally a nursing home. Ms. Merwin, coauthor of “The Informed Patient,” said her father was taking a long list of medications, and she often asked his primary care doctor for a medication review.
“I felt that my father at his age and his frailty didn’t need as many meds as he was on,” said Ms. Merwin, who lives in Long Island, N.Y. “So we went over his meds, and I asked, ‘Does he really need to be on this?’ ‘Does he really need to be on that?’ ”
She questioned one medication in particular, a statin to lower his cholesterol and risk of a heart attack.
“I thought possibly the statin was causing some myalgia, some muscle aches in his legs, which is why I advocated for coming off it,” she said.
The primary care doctor discontinued the anticholesterol drug.
Local pharmacies can also serve as a starting point for older adults and caregivers, where a pharmacist can give them more information on whether a particular combination of the medications taken may be harmful. In states that allow for pharmacists to prescribe some medications, pharmacists may be able to consolidate some of the medications or advise that a patient stop taking one or more, Dr. Vordenberg said.
“All pharmacists have the training to do a comprehensive medication review,” she said. “All pharmacists have the ability to follow up with the patient to find out how the deprescribing is going.”
Ms. Merwin’s parents received their prescriptions from a “small mom-and-pop pharmacy, where they were on a first-name basis with the pharmacist who really looked out for them. So they had that expertise available to them,” she said.
With information in hand on potentially unnecessary medications, the work of shedding medications should be done along with health care providers, some of whom prescribed the medications in the first place.
Many older adults live in geographically isolated areas without pharmacies, or receive prescriptions from mail-order pharmacies. In this case, Medicare plans offer free medication reviews with a doctor or pharmacist – known as a medication therapy management program – and provide recommendations for taking each drug.
Ms. Merwin’s father died in early 2020. She sometimes questions whether he should have stayed on the statin for longer, or if the doctor agreed too quickly without doing more research. But overall, she doesn’t regret raising the question with his health care providers, and she advises other caregivers and older adults to pay attention to medication lists.
“It’s dangerous to be passive when it comes to one’s health care now,” Ms. Merwin said. “That’s a difficult message for older adults to hear because they have grown up with the primacy of the doctor and the authority of the doctor, as opposed to it being a collaborative relationship.”
A version of this article first appeared on WebMD.com.
New study backs up capecitabine dosing practice in metastatic BC
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
FROM ASCO 2023
Ticagrelor may reduce brain lesions after carotid stenting
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM ESOC 2023
New EULAR lupus recommendations advise using biologics, tapering steroids
MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).
Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.
The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.
“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.
Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.
Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”
Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.
Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics
Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.
Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.
But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”
This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).
“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”
Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”
Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.
Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”
Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
Lupus nephritis
Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.
Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).
“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”
He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.
“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”
Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.
Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.
Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations
Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.
There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.
Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.
“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m2,” he remarked, completing his detailed discussion of the updated recommendations.
Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.
MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).
Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.
The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.
“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.
Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.
Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”
Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.
Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics
Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.
Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.
But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”
This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).
“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”
Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”
Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.
Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”
Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
Lupus nephritis
Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.
Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).
“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”
He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.
“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”
Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.
Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.
Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations
Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.
There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.
Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.
“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m2,” he remarked, completing his detailed discussion of the updated recommendations.
Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.
MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).
Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.
The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.
“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.
Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.
Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”
Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.
Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics
Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.
Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.
But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”
This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).
“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”
Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”
Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.
Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”
Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
Lupus nephritis
Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.
Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).
“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”
He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.
“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”
Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.
Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.
Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations
Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.
There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.
Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.
“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m2,” he remarked, completing his detailed discussion of the updated recommendations.
Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.
AT EULAR 2023
FDA OKs Injectafer for iron deficiency anemia in heart failure
“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.
Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.
The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.
In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.
No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.
According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.
A version of this article first appeared on Medscape.com.
“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.
Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.
The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.
In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.
No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.
According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.
A version of this article first appeared on Medscape.com.
“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.
Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.
The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.
In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.
No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.
According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.
A version of this article first appeared on Medscape.com.
Abrocitinib remains effective at 96 weeks, in older as well as younger adults
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
AT RAD 2023
Oral drug for brain tumor could change treatment landscape
say researchers reporting new results that could potentially change the treatment landscape.
The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.
Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.
The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).
Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.
The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.
Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.
The study was published online in the New England Journal of Medicine to coincide with the presentation.
“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.
“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.
“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
Brain-penetrating oral drug
Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.
Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.
Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.
Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
Study details
The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.
Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.
After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.
At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.
The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.
The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).
Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.
Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.
The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
say researchers reporting new results that could potentially change the treatment landscape.
The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.
Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.
The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).
Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.
The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.
Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.
The study was published online in the New England Journal of Medicine to coincide with the presentation.
“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.
“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.
“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
Brain-penetrating oral drug
Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.
Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.
Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.
Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
Study details
The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.
Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.
After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.
At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.
The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.
The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).
Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.
Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.
The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
say researchers reporting new results that could potentially change the treatment landscape.
The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.
Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.
The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).
Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.
The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.
Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.
The study was published online in the New England Journal of Medicine to coincide with the presentation.
“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.
“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.
“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
Brain-penetrating oral drug
Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.
Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.
Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.
Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
Study details
The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.
Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.
After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.
At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.
The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.
The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).
Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.
Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.
The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
AT ASCO 2023