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$150K: Average industry payment to top 1% of oncologists
A small number of U.S. medical oncologists make more than $100,000 a year in general payments from drug companies, a new study shows.
These high-payment physicians represent just 1% of all U.S. medical oncologists, yet they account for 37% of industry payments. These oncologists often hold important leadership positions, draft treatment guidelines, and sit on journal editorial boards.
The findings highlight a risk for “perceived and real conflict of interest,” corresponding author Christopher Booth, MD, of Queen’s University Cancer Research Center, Kingston, Ont., said in an interview. “Because of the leadership positions they hold, the potential impact of this small group of physicians on oncology practice and policy may be substantial.”
The study was published online in JCO Oncology Practice.
‘We have a problem’
It’s no secret that many oncologists have financial relationships with pharmaceutical companies. They receive payments for research initiatives, but they also receive more general, personal payments in the form of honoraria, consultant fees, gifts, and reimbursement for travel and meals.
Prior studies have shown that these payments are typically modest, but a small subset of medical oncologists receive more than $100,000 annually. Dr. Booth and colleagues wanted to know more about the characteristics of these “high-payment” oncologists.
Using the national Open Payments database, the researchers identified a total of 139 medical oncologists who practice in the United States and who received $100,000 or more in general payments linked to cancer medications in 2018.
In U.S. dollars, the median payment was $154,613, and the total was $24.2 million.
The majority (95%) of high-payment oncologists were active in clinical work, 56% worked in an academic setting, 31% worked at National Cancer Institute–designated cancer centers, and 23% worked at National Comprehensive Cancer Network (NCCN) centers.
Many were based in California (17%), Texas (12%), Florida (10%), and New York (8%).
Most currently hold or have held hospital leadership positions (60%) or faculty appointments (72%) and 21% have held leadership positions in specialty associations in the past 5 years. Nearly one-quarter (24%) have served on journal editorial boards, and 10% have authored clinical practice guidelines in the past 5 years.
More specifically, three physicians authored NCCN guidelines, and two authored American Society of Clinical Oncology guidelines during 2016-2021; one guideline was published in 2018 when payments were made.
“Oncology specialty associations, guideline panels, and journal editorial boards should reconsider if it is appropriate for physicians with such large payments to hold these high-profile positions,” Dr. Booth said.
Following publication of the study, some oncologists took to Twitter with reactions, including Manni Mohyuddin, MD (@ManniMD1), from the Huntsman Cancer Institute, University of Utah, Salt Lake City, who wrote: “I recognize that some conflict of interest ‘may’ be unavoidable in order to run trials. But when greater than TWICE the average American household annual salary is taken in payments from industry by those in leadership/editorial roles, we have a problem.”
Weighing in on the results, ASCO CEO Clifford A. Hudis, MD, told this news organization that the “limitations of the study make it difficult to draw conclusions about the scope or potential impact of these payments on care.”
For example, he explained, some payments attributed to individuals may have been made directly to the physicians’ institutions or employers for sponsored research expenses.
Dr. Hudis also noted that the payments examined in the study were made in 2018, whereas the potentially relevant leadership positions could have been attained at a different time.
Furthermore, in 2020, an editorial appeared in Cancer, showing that errors in Open Payments are “fairly common,” Dr. Hudis said. It’s also unclear whether the reported financial relationships were appropriately disclosed and were managed at the time under relevant conflict of interest policies, he said.
“The question left unanswered by this study is whether or not these relationships influence patient care,” said Dr. Hudis. He noted that decisions about care should come from physicians and patients who are informed of the best available, unbiased, peer-reviewed, scientific evidence.
“The potential impact of financial conflicts of interest on this effort is an issue of concern, even if this study does not directly address it,” Dr. Hudis said.
The study had no specific funding. Dr. Booth has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article. Dr. Hudis has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A small number of U.S. medical oncologists make more than $100,000 a year in general payments from drug companies, a new study shows.
These high-payment physicians represent just 1% of all U.S. medical oncologists, yet they account for 37% of industry payments. These oncologists often hold important leadership positions, draft treatment guidelines, and sit on journal editorial boards.
The findings highlight a risk for “perceived and real conflict of interest,” corresponding author Christopher Booth, MD, of Queen’s University Cancer Research Center, Kingston, Ont., said in an interview. “Because of the leadership positions they hold, the potential impact of this small group of physicians on oncology practice and policy may be substantial.”
The study was published online in JCO Oncology Practice.
‘We have a problem’
It’s no secret that many oncologists have financial relationships with pharmaceutical companies. They receive payments for research initiatives, but they also receive more general, personal payments in the form of honoraria, consultant fees, gifts, and reimbursement for travel and meals.
Prior studies have shown that these payments are typically modest, but a small subset of medical oncologists receive more than $100,000 annually. Dr. Booth and colleagues wanted to know more about the characteristics of these “high-payment” oncologists.
Using the national Open Payments database, the researchers identified a total of 139 medical oncologists who practice in the United States and who received $100,000 or more in general payments linked to cancer medications in 2018.
In U.S. dollars, the median payment was $154,613, and the total was $24.2 million.
The majority (95%) of high-payment oncologists were active in clinical work, 56% worked in an academic setting, 31% worked at National Cancer Institute–designated cancer centers, and 23% worked at National Comprehensive Cancer Network (NCCN) centers.
Many were based in California (17%), Texas (12%), Florida (10%), and New York (8%).
Most currently hold or have held hospital leadership positions (60%) or faculty appointments (72%) and 21% have held leadership positions in specialty associations in the past 5 years. Nearly one-quarter (24%) have served on journal editorial boards, and 10% have authored clinical practice guidelines in the past 5 years.
More specifically, three physicians authored NCCN guidelines, and two authored American Society of Clinical Oncology guidelines during 2016-2021; one guideline was published in 2018 when payments were made.
“Oncology specialty associations, guideline panels, and journal editorial boards should reconsider if it is appropriate for physicians with such large payments to hold these high-profile positions,” Dr. Booth said.
Following publication of the study, some oncologists took to Twitter with reactions, including Manni Mohyuddin, MD (@ManniMD1), from the Huntsman Cancer Institute, University of Utah, Salt Lake City, who wrote: “I recognize that some conflict of interest ‘may’ be unavoidable in order to run trials. But when greater than TWICE the average American household annual salary is taken in payments from industry by those in leadership/editorial roles, we have a problem.”
Weighing in on the results, ASCO CEO Clifford A. Hudis, MD, told this news organization that the “limitations of the study make it difficult to draw conclusions about the scope or potential impact of these payments on care.”
For example, he explained, some payments attributed to individuals may have been made directly to the physicians’ institutions or employers for sponsored research expenses.
Dr. Hudis also noted that the payments examined in the study were made in 2018, whereas the potentially relevant leadership positions could have been attained at a different time.
Furthermore, in 2020, an editorial appeared in Cancer, showing that errors in Open Payments are “fairly common,” Dr. Hudis said. It’s also unclear whether the reported financial relationships were appropriately disclosed and were managed at the time under relevant conflict of interest policies, he said.
“The question left unanswered by this study is whether or not these relationships influence patient care,” said Dr. Hudis. He noted that decisions about care should come from physicians and patients who are informed of the best available, unbiased, peer-reviewed, scientific evidence.
“The potential impact of financial conflicts of interest on this effort is an issue of concern, even if this study does not directly address it,” Dr. Hudis said.
The study had no specific funding. Dr. Booth has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article. Dr. Hudis has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A small number of U.S. medical oncologists make more than $100,000 a year in general payments from drug companies, a new study shows.
These high-payment physicians represent just 1% of all U.S. medical oncologists, yet they account for 37% of industry payments. These oncologists often hold important leadership positions, draft treatment guidelines, and sit on journal editorial boards.
The findings highlight a risk for “perceived and real conflict of interest,” corresponding author Christopher Booth, MD, of Queen’s University Cancer Research Center, Kingston, Ont., said in an interview. “Because of the leadership positions they hold, the potential impact of this small group of physicians on oncology practice and policy may be substantial.”
The study was published online in JCO Oncology Practice.
‘We have a problem’
It’s no secret that many oncologists have financial relationships with pharmaceutical companies. They receive payments for research initiatives, but they also receive more general, personal payments in the form of honoraria, consultant fees, gifts, and reimbursement for travel and meals.
Prior studies have shown that these payments are typically modest, but a small subset of medical oncologists receive more than $100,000 annually. Dr. Booth and colleagues wanted to know more about the characteristics of these “high-payment” oncologists.
Using the national Open Payments database, the researchers identified a total of 139 medical oncologists who practice in the United States and who received $100,000 or more in general payments linked to cancer medications in 2018.
In U.S. dollars, the median payment was $154,613, and the total was $24.2 million.
The majority (95%) of high-payment oncologists were active in clinical work, 56% worked in an academic setting, 31% worked at National Cancer Institute–designated cancer centers, and 23% worked at National Comprehensive Cancer Network (NCCN) centers.
Many were based in California (17%), Texas (12%), Florida (10%), and New York (8%).
Most currently hold or have held hospital leadership positions (60%) or faculty appointments (72%) and 21% have held leadership positions in specialty associations in the past 5 years. Nearly one-quarter (24%) have served on journal editorial boards, and 10% have authored clinical practice guidelines in the past 5 years.
More specifically, three physicians authored NCCN guidelines, and two authored American Society of Clinical Oncology guidelines during 2016-2021; one guideline was published in 2018 when payments were made.
“Oncology specialty associations, guideline panels, and journal editorial boards should reconsider if it is appropriate for physicians with such large payments to hold these high-profile positions,” Dr. Booth said.
Following publication of the study, some oncologists took to Twitter with reactions, including Manni Mohyuddin, MD (@ManniMD1), from the Huntsman Cancer Institute, University of Utah, Salt Lake City, who wrote: “I recognize that some conflict of interest ‘may’ be unavoidable in order to run trials. But when greater than TWICE the average American household annual salary is taken in payments from industry by those in leadership/editorial roles, we have a problem.”
Weighing in on the results, ASCO CEO Clifford A. Hudis, MD, told this news organization that the “limitations of the study make it difficult to draw conclusions about the scope or potential impact of these payments on care.”
For example, he explained, some payments attributed to individuals may have been made directly to the physicians’ institutions or employers for sponsored research expenses.
Dr. Hudis also noted that the payments examined in the study were made in 2018, whereas the potentially relevant leadership positions could have been attained at a different time.
Furthermore, in 2020, an editorial appeared in Cancer, showing that errors in Open Payments are “fairly common,” Dr. Hudis said. It’s also unclear whether the reported financial relationships were appropriately disclosed and were managed at the time under relevant conflict of interest policies, he said.
“The question left unanswered by this study is whether or not these relationships influence patient care,” said Dr. Hudis. He noted that decisions about care should come from physicians and patients who are informed of the best available, unbiased, peer-reviewed, scientific evidence.
“The potential impact of financial conflicts of interest on this effort is an issue of concern, even if this study does not directly address it,” Dr. Hudis said.
The study had no specific funding. Dr. Booth has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article. Dr. Hudis has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JCO ONCOLOGY PRACTICE
COVID vaccination in DMT-treated MS patients: New data
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.
AT CMSC 2022
FDA okays cancer drugs faster than EMA. But at what cost?
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.
“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.
“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.
“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.
FROM JAMA NETWORK OPEN
What’s the best time of day to exercise? It depends on your goals
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
FROM FRONTIERS IN PHYSIOLOGY
Venetoclax combos prolong progression-free CLL survival
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EHA 2022
How we treat acute pain could be wrong
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
FROM SCIENCE TRANSLATIONAL MEDICINE
New treatment reduces risk of anal cancer in people with HIV
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.
Experts elevate new drugs for diabetic kidney disease
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.
AT ADA 2022
Diabetes tied to risk of long COVID, too
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.”
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.”
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.”
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.
FROM ADA 2022
Prediabetes is linked independently to myocardial infarction
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.
FROM ENDO 2022