Clinical Topics & News

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.

However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.

sodapix/thinkstockphotos.com

These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.

“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.

“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.

“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.

“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.

“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.

On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.

But he noted that the task force did not find any significant harms from taking multivitamins.

“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.

Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.

“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
 

‘Any benefit likely to be small’

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.

The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
 

Possible benefit for older adults?

Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”

However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.

“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.

Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.

But do quicker review times translate to wins for patients?

“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”

Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.

In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.

The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.

Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.

“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.

In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.

“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.

Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”

“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”

The author of an invited commentary in JAMA Network Open had a different take on the study findings.

“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.

Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.

Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”

The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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

Although breast cancer occurs less frequently in Black women, compared with White women, they have a much higher risk of dying from the disease.

In the United States, age-adjusted breast cancer mortality between 2014 and 2018 was approximately 40% higher among Black women than among non-Hispanic White women.

This mortality gap likely reflects the fact that Black women face substantial barriers to obtaining timely, high-quality medical care, compared with White women, lead author Ismail Jatoi, MD, PhD, University of Texas Health Science Center, San Antonio, and colleagues suggest in a recent opinion piece.

The article was published online  in The New England Journal of Medicine.

When the team examined the statistics for breast cancer mortality, they found a surprise: The mortality gap between races only dates back to 1980.

Prior to 1980, mortality from breast cancer among Black women was slightly lower than White women, Dr. Jatoi and colleagues point out.

That year was a turning point in breast cancer management, as in 1980, both mammography screening and adjuvant endocrine therapy became available.

This was also when the mortality gap between the races started to show up.

It was disparities in access to the two new interventions that precipitated the divergence, as the authors suggest. Why this occurred is fairly self-evident, they comment.

“Black women are more likely than White women to lack health insurance or to have inadequate coverage, which has limited their access to mammography screening and adversely affected therapeutic decisionmaking,” researchers point out.

Moreover, both mammography screening and endocrine therapy primarily benefit patients with hormone receptor (HR)-positive breast cancer, which is equally common in Black and White patients. However, Black women have a 65% higher rate of HR-negative cancers than White women – and HR-negative tumors are often detected during the interval between mammography screening exams as palpable cancers.

Black women also have an 81% higher rate of triple-negative breast cancer, so they have benefited less from mammography screening and adjuvant endocrine therapy, both of which favor the detection and treatment of HR-positive breast cancer, the authors emphasize.

Some have suggested that the excess HR-negative breast cancer in Black women might be explained by hereditary factors. Yet as Dr. Jatoi and colleagues point out, the incidence of HR-negative breast cancer has actually been falling across all races in the United States since 1992.

However, the declines have been slower among Black women, and reductions in its incidence have been smaller among White women living in less affluent regions of the United States compared with White women from more affluent regions.

These patterns suggest that social determinants of health influence not only access to and quality of health care but also the development of HR-negative breast cancers, as the authors observe.

“If all people with breast cancer benefited equally from effective medical interventions, racial differences in mortality for individual tumor subtypes would largely reflect differences in incidence,” Dr. Jatoi and colleagues continue.

Yet the statistics show that the substantial racial disparities in mortality for both HR-positive and HR-negative cancers between Black and White women cannot be explained by differences in the incidence of either tumor alone, they write.

For example, mortality for HR-positive breast cancer is 19% higher among Black women than among White women, yet the incidence of HR-positive breast cancer is 22% lower among Black women.

Similarly, mortality from HR-negative breast cancer is over twice as high among Black women as it is among White women – a substantially larger disparity, compared with the 65% relative difference in the incidence of HR-negative breast cancer between the two races.

“Universal health care coverage could reduce disparities in treatment for cancers of all subtypes, including triple-negative breast cancer,” Dr. Jatoi and colleagues emphasize.

“Ensuring universal access to high-quality medical care can substantially narrow the racial disparity in U.S. breast-cancer mortality,” they conclude. 

The authors have reported no relevant financial relationships.

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

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

It all began with the question, “Has your butt been getting enough attention?”

Though that may seem unorthodox, it led researchers to discovering a treatment that may help prevent anal cancer in people with HIV/AIDS. It’s still featured on their study’s website, with this further explanation: “You get your viral load checked, your T-cell count checked, but what about your anus? Did you know that half of HIV+ men have cell changes in their anus caused by HPV?”

The Anal Cancer/HSIL Outcomes Research (ANCHOR) study, led by Joel Palefsky, MD, was published  in The New England Journal of Medicine. Dr. Palefsky, an infectious disease expert at the University of California, San Francisco, and his team set out to determine whether a treatment that prevents cervical cancer in people with human papillomavirus (HPV) would benefit people with HIV/AIDS. The new treatment reduced the likelihood of anal cancer by more than 50%.

The team worked over 7 years, during which time they tested 4,459 men, women, transgender, and nonbinary individuals at 25 sites across the United States. The participants were sorted into two groups: Some received treatment for high-grade squamous intraepithelial lesions (HSILs), and some did not but were monitored for signs of disease. These included individuals over 35 who were living with HIV/AIDS and who were found to have patches of abnormal cells in their rectal lining.

HSILs are the cells gynecologists look for in performing a pap smear. They are precancerous cells commonly found in the cervix of persons with HPV. Finding HSILs during a gynecologic examination alerts clinicians to potential problems.

HSILs can also be found in the anal tract of men and women with HIV. Dr. Palefsky therefore hypothesized that, as with HPV and cervical cancer, these anal HSILs may be a precursor of anal cancer.

The scientists decided to treat these cells the same way they would treat them if found in the cervix and to see whether that reduced the risk of cancer. Doctors used lidocaine to numb the area, then removed the HSILs with an electric probe. The team then assessed whether the treatment prevented people from getting cancer.

It turns out that in many cases, it did. The study concluded after 30 of the participants developed anal cancer. Of those, 21 patients had not received HSIL treatment, compared with nine who did receive the treatment. The treatment resulted in a 57% reduction in the rate of anal cancer among patients who received treatment for their HSILs.

These results are encouraging, said Aasma Shaukat, MD, director of outcomes research in the Division of Gastroenterology and Hepatology at NYU Langone Health. Dr. Shaukat was not involved with the study. She believes it’s going to cause ripples across the field.

“The study is likely to change guidelines in favor of active and early treatment for HSIL and away from watchful waiting in individuals living with HIV to reduce the risk of developing anal squamous cell carcinoma, akin to removing polyps during colonoscopy to progression to and incidence of colorectal cancer,” she said in an email interview.

Treatments for this group of patients are more important now than ever. Since the beginning of the AIDS epidemic in the 1980s, the number of people with HIV has increased, Dr. Palefsky detailed in a press conference announcing the ANCHOR results. That’s partially because of new transmissions and partially owing to the fact that new treatments make it possible for people with HIV to live long, healthy lives. So as more people with HIV move into their sunset years, there are more people at risk for developing cancer, which is a disease associated with aging. Anal cancer sits at the intersection of risk for aging people who have HIV.

Any defense we have against the risk of cancer in this growing demographic is a good thing, says Hanna K. Sanoff, MD, a gastrointestinal oncologist at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who was also not involved in the study. Although it’s not ready to be applied in doctors’ offices now, it could be a tool in the future. “Anything we can do to try and decrease the chance of precancerous lesions progressing to a real invasive cancer is of great importance. This kind of prevention work is critical to helping minimize the burden of cancer on our communities,” Dr. Sanoff said in an interview.

The study was funded by the National Cancer Institute of the National Institutes of Health and was conducted through the NCI-supported AIDS Malignancy Consortium. Dr. Shaukat and Dr. Sanoff report no relevant financial relationships.

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

It all began with the question, “Has your butt been getting enough attention?”

Though that may seem unorthodox, it led researchers to discovering a treatment that may help prevent anal cancer in people with HIV/AIDS. It’s still featured on their study’s website, with this further explanation: “You get your viral load checked, your T-cell count checked, but what about your anus? Did you know that half of HIV+ men have cell changes in their anus caused by HPV?”

The Anal Cancer/HSIL Outcomes Research (ANCHOR) study, led by Joel Palefsky, MD, was published  in The New England Journal of Medicine. Dr. Palefsky, an infectious disease expert at the University of California, San Francisco, and his team set out to determine whether a treatment that prevents cervical cancer in people with human papillomavirus (HPV) would benefit people with HIV/AIDS. The new treatment reduced the likelihood of anal cancer by more than 50%.

The team worked over 7 years, during which time they tested 4,459 men, women, transgender, and nonbinary individuals at 25 sites across the United States. The participants were sorted into two groups: Some received treatment for high-grade squamous intraepithelial lesions (HSILs), and some did not but were monitored for signs of disease. These included individuals over 35 who were living with HIV/AIDS and who were found to have patches of abnormal cells in their rectal lining.

HSILs are the cells gynecologists look for in performing a pap smear. They are precancerous cells commonly found in the cervix of persons with HPV. Finding HSILs during a gynecologic examination alerts clinicians to potential problems.

HSILs can also be found in the anal tract of men and women with HIV. Dr. Palefsky therefore hypothesized that, as with HPV and cervical cancer, these anal HSILs may be a precursor of anal cancer.

The scientists decided to treat these cells the same way they would treat them if found in the cervix and to see whether that reduced the risk of cancer. Doctors used lidocaine to numb the area, then removed the HSILs with an electric probe. The team then assessed whether the treatment prevented people from getting cancer.

It turns out that in many cases, it did. The study concluded after 30 of the participants developed anal cancer. Of those, 21 patients had not received HSIL treatment, compared with nine who did receive the treatment. The treatment resulted in a 57% reduction in the rate of anal cancer among patients who received treatment for their HSILs.

These results are encouraging, said Aasma Shaukat, MD, director of outcomes research in the Division of Gastroenterology and Hepatology at NYU Langone Health. Dr. Shaukat was not involved with the study. She believes it’s going to cause ripples across the field.

“The study is likely to change guidelines in favor of active and early treatment for HSIL and away from watchful waiting in individuals living with HIV to reduce the risk of developing anal squamous cell carcinoma, akin to removing polyps during colonoscopy to progression to and incidence of colorectal cancer,” she said in an email interview.

Treatments for this group of patients are more important now than ever. Since the beginning of the AIDS epidemic in the 1980s, the number of people with HIV has increased, Dr. Palefsky detailed in a press conference announcing the ANCHOR results. That’s partially because of new transmissions and partially owing to the fact that new treatments make it possible for people with HIV to live long, healthy lives. So as more people with HIV move into their sunset years, there are more people at risk for developing cancer, which is a disease associated with aging. Anal cancer sits at the intersection of risk for aging people who have HIV.

Any defense we have against the risk of cancer in this growing demographic is a good thing, says Hanna K. Sanoff, MD, a gastrointestinal oncologist at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who was also not involved in the study. Although it’s not ready to be applied in doctors’ offices now, it could be a tool in the future. “Anything we can do to try and decrease the chance of precancerous lesions progressing to a real invasive cancer is of great importance. This kind of prevention work is critical to helping minimize the burden of cancer on our communities,” Dr. Sanoff said in an interview.

The study was funded by the National Cancer Institute of the National Institutes of Health and was conducted through the NCI-supported AIDS Malignancy Consortium. Dr. Shaukat and Dr. Sanoff report no relevant financial relationships.

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

It all began with the question, “Has your butt been getting enough attention?”

Though that may seem unorthodox, it led researchers to discovering a treatment that may help prevent anal cancer in people with HIV/AIDS. It’s still featured on their study’s website, with this further explanation: “You get your viral load checked, your T-cell count checked, but what about your anus? Did you know that half of HIV+ men have cell changes in their anus caused by HPV?”

The Anal Cancer/HSIL Outcomes Research (ANCHOR) study, led by Joel Palefsky, MD, was published  in The New England Journal of Medicine. Dr. Palefsky, an infectious disease expert at the University of California, San Francisco, and his team set out to determine whether a treatment that prevents cervical cancer in people with human papillomavirus (HPV) would benefit people with HIV/AIDS. The new treatment reduced the likelihood of anal cancer by more than 50%.

The team worked over 7 years, during which time they tested 4,459 men, women, transgender, and nonbinary individuals at 25 sites across the United States. The participants were sorted into two groups: Some received treatment for high-grade squamous intraepithelial lesions (HSILs), and some did not but were monitored for signs of disease. These included individuals over 35 who were living with HIV/AIDS and who were found to have patches of abnormal cells in their rectal lining.

HSILs are the cells gynecologists look for in performing a pap smear. They are precancerous cells commonly found in the cervix of persons with HPV. Finding HSILs during a gynecologic examination alerts clinicians to potential problems.

HSILs can also be found in the anal tract of men and women with HIV. Dr. Palefsky therefore hypothesized that, as with HPV and cervical cancer, these anal HSILs may be a precursor of anal cancer.

The scientists decided to treat these cells the same way they would treat them if found in the cervix and to see whether that reduced the risk of cancer. Doctors used lidocaine to numb the area, then removed the HSILs with an electric probe. The team then assessed whether the treatment prevented people from getting cancer.

It turns out that in many cases, it did. The study concluded after 30 of the participants developed anal cancer. Of those, 21 patients had not received HSIL treatment, compared with nine who did receive the treatment. The treatment resulted in a 57% reduction in the rate of anal cancer among patients who received treatment for their HSILs.

These results are encouraging, said Aasma Shaukat, MD, director of outcomes research in the Division of Gastroenterology and Hepatology at NYU Langone Health. Dr. Shaukat was not involved with the study. She believes it’s going to cause ripples across the field.

“The study is likely to change guidelines in favor of active and early treatment for HSIL and away from watchful waiting in individuals living with HIV to reduce the risk of developing anal squamous cell carcinoma, akin to removing polyps during colonoscopy to progression to and incidence of colorectal cancer,” she said in an email interview.

Treatments for this group of patients are more important now than ever. Since the beginning of the AIDS epidemic in the 1980s, the number of people with HIV has increased, Dr. Palefsky detailed in a press conference announcing the ANCHOR results. That’s partially because of new transmissions and partially owing to the fact that new treatments make it possible for people with HIV to live long, healthy lives. So as more people with HIV move into their sunset years, there are more people at risk for developing cancer, which is a disease associated with aging. Anal cancer sits at the intersection of risk for aging people who have HIV.

Any defense we have against the risk of cancer in this growing demographic is a good thing, says Hanna K. Sanoff, MD, a gastrointestinal oncologist at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who was also not involved in the study. Although it’s not ready to be applied in doctors’ offices now, it could be a tool in the future. “Anything we can do to try and decrease the chance of precancerous lesions progressing to a real invasive cancer is of great importance. This kind of prevention work is critical to helping minimize the burden of cancer on our communities,” Dr. Sanoff said in an interview.

The study was funded by the National Cancer Institute of the National Institutes of Health and was conducted through the NCI-supported AIDS Malignancy Consortium. Dr. Shaukat and Dr. Sanoff report no relevant financial relationships.

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

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.