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Expert shares hyperhidrosis treatment pearls
Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.
Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.
A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.
“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”
The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.
“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.
Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.
“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”
Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.
There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”
He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.
For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”
For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.
On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.
A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”
Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.
Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.
Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.
A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.
“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”
The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.
“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.
Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.
“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”
Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.
There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”
He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.
For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”
For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.
On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.
A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”
Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.
Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.
Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.
A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.
“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”
The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.
“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.
Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.
“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”
Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.
There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”
He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.
For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”
For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.
On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.
A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”
Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.
FROM ODAC 2021
Bariatric surgery gives 10-year cure for some advanced diabetes
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
Oral contraceptives may reduce ovarian and endometrial cancer risk 35 years after discontinuation
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
FROM CANCER RESEARCH
Plant-based or keto diet? Novel study yields surprising results
For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.
In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.
“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.
The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.
In this study, Dr. Hall and colleagues tested these two hypotheses head to head.
“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.
“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”
The study was published online Jan. 21, 2021 in Nature Medicine.
Pros and cons to both diets
For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m2.
The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g−1), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g−1) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.
Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.
One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.
They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d−1, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.
Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.
“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.
“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.
Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.
“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.
“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
Diet ‘tribes’
In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.
“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”
Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”
The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.
In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.
“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.
The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.
In this study, Dr. Hall and colleagues tested these two hypotheses head to head.
“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.
“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”
The study was published online Jan. 21, 2021 in Nature Medicine.
Pros and cons to both diets
For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m2.
The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g−1), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g−1) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.
Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.
One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.
They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d−1, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.
Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.
“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.
“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.
Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.
“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.
“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
Diet ‘tribes’
In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.
“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”
Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”
The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
For appetite control, a low-fat, plant-based diet has advantages over a low-carbohydrate, animal-based ketogenic diet, although the keto diet wins when it comes to keeping post-meal glucose and insulin levels in check, new research suggests.
In a highly controlled crossover study conducted at the National Institutes of Health, people consumed fewer daily calories when on a low-fat, plant-based diet, but their insulin and blood glucose levels were higher than when they followed a low-carbohydrate, animal-based diet.
“There is this somewhat-outdated idea now that higher-fat diets, because they have more calories per gram, tend to make people overeat – something called the passive overconsumption model,” senior investigator Kevin Hall, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, said in an interview.
The other more popular model these days, he explained, is the carbohydrate-insulin model, which holds that following a diet high in carbohydrates and sugar that causes insulin levels to spike will increase hunger and cause a person to overeat.
In this study, Dr. Hall and colleagues tested these two hypotheses head to head.
“The short answer is that we got exactly the opposite predictions from the carbohydrate-insulin model of obesity. In other words, instead of making people eat more and gaining weight and body fat, they actually ended up eating less on that diet and losing body fat compared to the higher-fat diet,” Dr. Hall said.
“Yet, the passive overconsumption model also failed, because despite them eating a very energy-dense diet and high fat, they didn’t gain weight and gain body fat. And so both of these models of why people overeat and gain weight seem to be inadequate in our study,” he said. “This suggests that things are a little bit more complicated.”
The study was published online Jan. 21, 2021 in Nature Medicine.
Pros and cons to both diets
For the study, the researchers housed 20 healthy adults who did not have diabetes for 4 continuous weeks at the NIH Clinical Center. The mean age of the participants was 29.9 years, and the mean body mass index was 27.8 kg/m2.
The participants were randomly allocated to consume ad libitum either a plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with low-energy density (about 1 kcal/g−1), or an animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with high energy density (about 2 kcal/g−1) for 2 weeks. They then crossed over to the alternate diet for 2 weeks.
Both diets contained about 14% protein and were matched for total calories, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. Participants could eat what and however much they chose of the meals they were given.
One participant withdrew, owing to hypoglycemia during the low-carbohydrate diet phase. For the primary outcome, the researchers compared mean daily ad libitum energy intake between each 2-week diet period.
They found that energy intake from the low-fat diet was reduced by approximately 550-700 kcal/d−1, compared with the low-carbohydrate keto diet. Yet, despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets.
Participants lost weight on both diets (about 1-2 kg on average), but only the low-fat diet led to a significant loss of body fat.
“Interestingly, our findings suggest benefits to both diets, at least in the short term,” Dr. Hall said in a news release.
“While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels. We don’t yet know if these differences would be sustained over the long term,” he said.
Dr. Hall added that it’s important to note that the study was not designed to make diet recommendations for weight loss, and the results might have been different had the participants been actively trying to lose weight.
“In fact, they didn’t even know what the study was about; we just said we want you to eat the two diets, and we’re going to see what happens in your body either as you eat as much or as little as you want,” he said.
“It’s a bit of a mixed bag in terms of which diet might be better for an individual. I think you can interpret this study as that there are positives and negatives for both diets,” Dr. Hall said.
Diet ‘tribes’
In a comment, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said it’s important to note that “a ‘low-carb diet’ has yet to be defined, and many definitions exist.
“We really need a standard definition of what constitutes ‘low-carb’ so that studies can be designed and evaluated in a consistent manner. It’s problematic because, without a standard definition, the ‘diet tribe’ researchers (keto versus plant-based) always seem to find the answer that is in their own favor,” Dr. Wallace said. “This study does seem to use less than 20 grams of carbs per day, which in my mind is pretty low carb.”
Perhaps the most important caveat, he added, is that, in the real world, “most people don’t adhere to these very strict diets – not even for 2 weeks.”
The study was supported by the NIDDK Intramural Research Program, with additional NIH support from a National Institute of Nursing Research grant. One author has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, serves on the scientific advisory council for Kerry Taste and Nutrition, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr. Hall and the other authors disclosed no relevant financial relationships. Dr. Wallace is principal and CEO of the Think Healthy Group, editor of the Journal of Dietary Supplements, and deputy editor of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
Patients with early arthritis may need tailored treatments
Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.
If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.
“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.
The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.
But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.
In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.
As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.
They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.
Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.
After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).
The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.
They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.
There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).
Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.
Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.
The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.
“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”
But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.
The authors and Dr. Deane have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.
If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.
“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.
The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.
But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.
In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.
As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.
They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.
Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.
After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).
The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.
They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.
There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).
Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.
Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.
The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.
“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”
But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.
The authors and Dr. Deane have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with early, undifferentiated arthritis may benefit from milder or stronger treatments, depending on the number of their risk factors for developing rheumatoid arthritis, researchers say.
If the finding is borne out by further research, clinicians could consider treating some of these patients with hydroxychloroquine, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) rather than methotrexate, said Pascal de Jong, MD, PhD, a rheumatologist at Erasmus Medical Center in Rotterdam, the Netherlands.
“Maybe those patients with fewer risk factors should get less intensive treatment,” he said in an interview. The study by de Jong and colleagues was published online Jan. 23 in Rheumatology.
The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate for patients who are at risk for persistent arthritis, which it says is “factually synonymous” with rheumatoid arthritis.
But these recommendations are based on studies involving patients with established rheumatoid arthritis, Dr. de Jong said.
In an earlier study, he and his colleagues found that hydroxychloroquine can be just as effective as methotrexate for patients newly diagnosed with rheumatoid arthritis who don’t have autoantibodies. This led them to wonder whether their findings might apply to some subgroups of patients with early arthritis.
As an initial test of this idea, they identified 130 patients from the Rotterdam Early Arthritis Cohort (tREACH) trial who had at least one swollen joint but who did meet the diagnostic criteria for rheumatoid arthritis.
They sorted the patients into groups on the basis of the number of risk factors for persistent arthritis. The risk factors were autoantibody positivity (rheumatoid factor and/or anticitrullinated protein antibody), polyarthritis (more than four swollen joints), erosive disease, and elevations in levels of acute-phase reactants.
Thirty-one patients had none of these risk factors, 66 patients had one risk factor, and the remaining 33 patients had at least two risk factors.
After 2 years of follow-up, 74% of the patients who had had no risk factors had recovered from their arthritis and had not taken disease-modifying antirheumatic drugs (DMARDs) for at least 6 months (DMARD-free remission). Among the patients who had had one risk factor, 48% achieved DMARD-free remission. Among those who had had two risk factors, 45% achieved DMARD-free remission. The differences between the group that had had no risk factors and the other two groups were statistically significant (P < .05).
The researchers found that those patients who had been experiencing their symptoms for fewer than 6 months were more likely to achieve disease-free remission.
They also sorted patients into different groups on the basis of the treatments they received. One group of 30 comprised all patients who had been initially treated with methotrexate and included patients who had also received other drugs. One group of 40 received hydroxychloroquine initially, and one group of 60 comprised patients who had received no DMARDs initially and included those who had received NSAIDs or glucocorticoids.
There was no statistically significant difference in DMARD-free remission rates among the treatment groups. However, among those patients who were not treated initially with DMARDs, the chance of sustaining DMARD-free remission for more than a year was lower in comparison with the patients who received methotrexate initially (odds ratio, 4.28; 95% confidence interval, 1.34-13.72; P < .05).
Those patients who had fewer baseline risk factors were more likely to have their medication dosages tapered, and they were at lower risk for flares. Patients with more risk factors were more likely to require an intensificiation of treatment, such as with the use of biologicals.
Methotrexate is more likely to cause side effects such as nausea, fatigue, and hair loss than hydroxychloroquine, Dr. de Jong said. “If the medication is better tolerated, it also influences the compliance of the patient,” he said.
The study could help rheumatologists determine which patients need the most aggressive treatment, agreed Kevin Deane, MD, PhD, associate professor of medicine, division of rheumatology, the University of Colorado, Aurora.
“That’s a common clinical problem,” he said. “Somebody comes in with sort of mild arthritis, and you don’t quite know what it is yet.”
But he added that more research is needed to understand what treatment works best for those patients whose arthritis has not yet been differentiated. Primary care physicians who suspect inflammatory arthritis should refer their patients to rheumatologists and should test for rheumatoid factors and anticyclic citrullinated peptide, Dr. Deane said.
The authors and Dr. Deane have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Aspirin linked to reduced bladder, breast cancer mortality
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.
“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open.
“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.
In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.
“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.
“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
Aspirin/cancer research in older people lacking
With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.
However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.
To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.
The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.
Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.
The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.
However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.
A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.
“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
Mechanism speculation focuses on COX-2 pathway
Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.
In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.
“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.
The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.
Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.
“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”
Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.
“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”
The study authors and Dr. McNeil disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Category 5’ COVID hurricane approaches, expert says
The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.
“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.
The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.
Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”
Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.
Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.
“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.
The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.
“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”
A version of this article first appeared on WebMD.com.
The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.
“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.
The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.
Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”
Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.
Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.
“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.
The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.
“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”
A version of this article first appeared on WebMD.com.
The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.
“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.
The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.
Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”
Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.
Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.
“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.
The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.
“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”
A version of this article first appeared on WebMD.com.
Tofacitinib for RA misses the mark in safety study
Daily treatment with tofacitinib (Xeljanz) led to more malignancies and adverse cardiovascular events in older rheumatoid arthritis patients compared with treatment with a tumor necrosis factor (TNF) inhibitor, according to the partial results of a safety study announced last week by Pfizer.
The postmarketing study known as ORAL Surveillance began in 2014 to evaluate the safety of the Janus kinase (JAK) inhibitor tofacitinib compared to a TNF inhibitor in RA patients 50 years of age or older with at least one additional cardiovascular risk factor. Its 4,362 participants were randomized to either daily doses of 5 mg (n = 1,455) or 10 mg (n = 1,456) of tofacitinib or the TNFi (n = 1,451), which was adalimumab for patients in the United States, Canada, and Puerto Rico, and etanercept elsewhere. During analysis, adverse events were pooled for all patients on tofacitinib.
Overall, 135 patients developed major adverse cardiovascular events (MACE) and 164 developed malignancies – excluding nonmelanoma skin cancer. The incidence of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNFi group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09). The rate of MACE was also higher in the combined tofacitinib group (0.98 vs. 0.73 per 100 person-years; HR, 1.33; 95% CI, 0.91-1.94). Both rates for tofacitinib did not meet the trial’s noninferiority criteria.
Among the patients on tofacitinib, the most reported MACE was myocardial infarction and the most reported malignancy was lung cancer. Study participants with noted risk factors – including older age and smoking – were more likely to experience adverse events.
In February 2019, patients in the 10-mg tofacitinib group were switched to the 5-mg because of a safety signal indicating increased risk of pulmonary embolism and death.
Tofacitinib was approved for RA in November 2012, though concerns about serious side effects had been noted during clinical trials and a boxed warning was ultimately added to the drug’s label. Tofacitinib is also approved for adults with active psoriatic arthritis, adults with moderately to severely active ulcerative colitis, and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis. Other JAK inhibitors such as baricitinib and upadacitinib have been approved for RA in the interim as well, though the higher dose of baricitinib was rejected in committee because of safety concerns and both their boxes also warn against infections, thrombosis, and cancer.
A postmarketing safety study on baricitinib is expected to be completed in 2025.
The full results of the ORAL Surveillance study – which should address safety regarding pulmonary embolism and mortality, as well as efficacy data – have not yet been released. “Pfizer is working with the [FDA] and other regulatory agencies to review the full results and analyses as they become available,” the press release said.
Daily treatment with tofacitinib (Xeljanz) led to more malignancies and adverse cardiovascular events in older rheumatoid arthritis patients compared with treatment with a tumor necrosis factor (TNF) inhibitor, according to the partial results of a safety study announced last week by Pfizer.
The postmarketing study known as ORAL Surveillance began in 2014 to evaluate the safety of the Janus kinase (JAK) inhibitor tofacitinib compared to a TNF inhibitor in RA patients 50 years of age or older with at least one additional cardiovascular risk factor. Its 4,362 participants were randomized to either daily doses of 5 mg (n = 1,455) or 10 mg (n = 1,456) of tofacitinib or the TNFi (n = 1,451), which was adalimumab for patients in the United States, Canada, and Puerto Rico, and etanercept elsewhere. During analysis, adverse events were pooled for all patients on tofacitinib.
Overall, 135 patients developed major adverse cardiovascular events (MACE) and 164 developed malignancies – excluding nonmelanoma skin cancer. The incidence of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNFi group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09). The rate of MACE was also higher in the combined tofacitinib group (0.98 vs. 0.73 per 100 person-years; HR, 1.33; 95% CI, 0.91-1.94). Both rates for tofacitinib did not meet the trial’s noninferiority criteria.
Among the patients on tofacitinib, the most reported MACE was myocardial infarction and the most reported malignancy was lung cancer. Study participants with noted risk factors – including older age and smoking – were more likely to experience adverse events.
In February 2019, patients in the 10-mg tofacitinib group were switched to the 5-mg because of a safety signal indicating increased risk of pulmonary embolism and death.
Tofacitinib was approved for RA in November 2012, though concerns about serious side effects had been noted during clinical trials and a boxed warning was ultimately added to the drug’s label. Tofacitinib is also approved for adults with active psoriatic arthritis, adults with moderately to severely active ulcerative colitis, and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis. Other JAK inhibitors such as baricitinib and upadacitinib have been approved for RA in the interim as well, though the higher dose of baricitinib was rejected in committee because of safety concerns and both their boxes also warn against infections, thrombosis, and cancer.
A postmarketing safety study on baricitinib is expected to be completed in 2025.
The full results of the ORAL Surveillance study – which should address safety regarding pulmonary embolism and mortality, as well as efficacy data – have not yet been released. “Pfizer is working with the [FDA] and other regulatory agencies to review the full results and analyses as they become available,” the press release said.
Daily treatment with tofacitinib (Xeljanz) led to more malignancies and adverse cardiovascular events in older rheumatoid arthritis patients compared with treatment with a tumor necrosis factor (TNF) inhibitor, according to the partial results of a safety study announced last week by Pfizer.
The postmarketing study known as ORAL Surveillance began in 2014 to evaluate the safety of the Janus kinase (JAK) inhibitor tofacitinib compared to a TNF inhibitor in RA patients 50 years of age or older with at least one additional cardiovascular risk factor. Its 4,362 participants were randomized to either daily doses of 5 mg (n = 1,455) or 10 mg (n = 1,456) of tofacitinib or the TNFi (n = 1,451), which was adalimumab for patients in the United States, Canada, and Puerto Rico, and etanercept elsewhere. During analysis, adverse events were pooled for all patients on tofacitinib.
Overall, 135 patients developed major adverse cardiovascular events (MACE) and 164 developed malignancies – excluding nonmelanoma skin cancer. The incidence of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNFi group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09). The rate of MACE was also higher in the combined tofacitinib group (0.98 vs. 0.73 per 100 person-years; HR, 1.33; 95% CI, 0.91-1.94). Both rates for tofacitinib did not meet the trial’s noninferiority criteria.
Among the patients on tofacitinib, the most reported MACE was myocardial infarction and the most reported malignancy was lung cancer. Study participants with noted risk factors – including older age and smoking – were more likely to experience adverse events.
In February 2019, patients in the 10-mg tofacitinib group were switched to the 5-mg because of a safety signal indicating increased risk of pulmonary embolism and death.
Tofacitinib was approved for RA in November 2012, though concerns about serious side effects had been noted during clinical trials and a boxed warning was ultimately added to the drug’s label. Tofacitinib is also approved for adults with active psoriatic arthritis, adults with moderately to severely active ulcerative colitis, and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis. Other JAK inhibitors such as baricitinib and upadacitinib have been approved for RA in the interim as well, though the higher dose of baricitinib was rejected in committee because of safety concerns and both their boxes also warn against infections, thrombosis, and cancer.
A postmarketing safety study on baricitinib is expected to be completed in 2025.
The full results of the ORAL Surveillance study – which should address safety regarding pulmonary embolism and mortality, as well as efficacy data – have not yet been released. “Pfizer is working with the [FDA] and other regulatory agencies to review the full results and analyses as they become available,” the press release said.
High cost of pancreatic enzymes a barrier for patients with cancer
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
First mammography guidelines for older breast cancer survivors
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.