Clinician Reviews

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

COPENHAGEN – Vedolizumab (ENTYVIO) a monoclonal antibody drug, shows a higher overall 1- and 2-year persistence of use – the overall time that a patient stays on a medication – compared with two anti–tumor necrosis factor inhibitors (anti-TNFi) in both Crohn’s disease and ulcerative colitis, according to the first meta-analysis of their real-world effectiveness.

The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.

“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.

The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.

In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).

“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.

Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”

“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.  

Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”   

A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu.  “These findings suggested that alternative biologics with high effectiveness should be considered.”

Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.

Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”

As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.

Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).

Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).

In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.

In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.

In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.

Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”  

Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”

“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.

“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.” 

Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
 

Physician interactions with nurse practitioners (NPs) and physician assistants (PAs) are only going to increase in frequency. – The U.S. Bureau of Labor Statistics forecasts a 40% increase in the NP workforce by 2031, coupled with a 28% rise in PAs.

In recent reports on the quality of the relationships involving these health care professions, survey respondents mostly gave positive accounts of collaboration, using words such as like “comradery,” “teamwork,” “congenial,” and “cohesion.” But all was not perfect. Where and how could these important health care provider relationships improve?
 

PAs: “Competition and collaboration’ with RNs

In a Medscape survey of more than 770 PAs about their working relationships with other health care professionals; 83% of them supported the idea of PAs and NPs practicing more independently from physicians, but sometimes it’s not easy to stay in their individual lanes.

One PA respondent complained that NPs get “more opportunities and preference,” another pointed to PA-NP “turf issues,” and a third griped about NPs’ “strong unions,” which have stoked more fighting about practice abilities and available settings.

Robert Blumm, MA, PA-C, a retired surgical and emergency medicine PA who regards himself as an advocate for both PAs and NPs, describes their interaction as a “mixture of competition and collaboration.”

On one hand, the two groups typically “cooperate and do an excellent job, incurring patient errors similar to or less than physician colleagues or senior residents.” On the other hand, Mr. Blumm conceded, there is some jealousy among PAs over NPs’ advantage in staffing and hiring decisions, “since they don’t need [direct physician] supervision ... and there are limits on how many PAs can be supervised by one physician.”

Most PA-NP interactions are collaborative, although many people emphasize the relatively few conflicts, said Jennifer Orozco, DMSc, PA-C, president and chair of the American Academy of PAs.

“We see that a lot in this country,” she said. “People try to drive a wedge, but it’s often a misnomer that there’s a lot of arguing and infighting.”
 

NPs: Different backgrounds, same goal

The Medscape survey also included information from 750 NPs on working relationships; 93% of them favored nurses and PAs working more independently from doctors.

April Kapu, DNP, ARPN, has worked closely with PAs for more than 20 years. “In my experience ... they complement one another as health team members, although the education and training are somewhat different,” said Ms. Kapu, , president of the American Association of Nurse Practitioners.

Some respondents noted the different educational trajectories for NPs and PAs. “Doctors and PAs are taught using the same model, but NPs are taught under the nursing model,” wrote a family medicine PA.

In emergency departments where Mr. Blumm has worked, ICU NPs have an edge over PAs in terms of preparation, organization, and the tabulation of formulas. On the other hand, some of Mr. Blumm’s fellow PAs were also emergency medicine technicians or respiratory therapists, who had “2 years of classroom training, on par with that of medical students.”

Must these differences in training and education foment conflict between NPs and PAs? “We all bring something different to the table,” said Ms. Kapu, who also is associate dean for clinical and community partnerships at Vanderbilt University, Nashville, Tenn. “It is important to respect each person’s entry point, education, and training.”
 

Differing personalities and environments

Numerous PA respondents said that individual personalities and work environments are more likely to trigger issues with NPs than are differences in training.

“It depends on the team and situation and who the people are, not the letters behind their names,” an emergency medicine PA wrote. A surgical PA noted that “group dynamics and work culture differ from place to place,” while a third PA agreed that “it’s personality dependent, not title dependent.”

No single formula will resolve areas of NP-PA conflict, Ms. Orozco said. “What works in Chicago might not work in rural Colorado or Texas or California, but we do have to come together. The overall focus should be on greater flexibility for PAs and NPs. Patients will fare better.”
 

Joint research, publishing could help

About a decade ago, Mr. Blumm joined with another PA and an NP to form the American College of Clinicians, the first joint PA-NP national professional organization. Although it disbanded after 6 years, owing to low membership, he hopes a similar collaboration will take off in the future.

“I also recommend that PAs and NPs publish articles together, with research as an excellent place to start,” he added. “PAs and NPs should stand together and be a source of healing for all our patients. Regardless of our titles, our responsibility is to bring healing together.”

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

Physician interactions with nurse practitioners (NPs) and physician assistants (PAs) are only going to increase in frequency. – The U.S. Bureau of Labor Statistics forecasts a 40% increase in the NP workforce by 2031, coupled with a 28% rise in PAs.

In recent reports on the quality of the relationships involving these health care professions, survey respondents mostly gave positive accounts of collaboration, using words such as like “comradery,” “teamwork,” “congenial,” and “cohesion.” But all was not perfect. Where and how could these important health care provider relationships improve?
 

PAs: “Competition and collaboration’ with RNs

In a Medscape survey of more than 770 PAs about their working relationships with other health care professionals; 83% of them supported the idea of PAs and NPs practicing more independently from physicians, but sometimes it’s not easy to stay in their individual lanes.

One PA respondent complained that NPs get “more opportunities and preference,” another pointed to PA-NP “turf issues,” and a third griped about NPs’ “strong unions,” which have stoked more fighting about practice abilities and available settings.

Robert Blumm, MA, PA-C, a retired surgical and emergency medicine PA who regards himself as an advocate for both PAs and NPs, describes their interaction as a “mixture of competition and collaboration.”

On one hand, the two groups typically “cooperate and do an excellent job, incurring patient errors similar to or less than physician colleagues or senior residents.” On the other hand, Mr. Blumm conceded, there is some jealousy among PAs over NPs’ advantage in staffing and hiring decisions, “since they don’t need [direct physician] supervision ... and there are limits on how many PAs can be supervised by one physician.”

Most PA-NP interactions are collaborative, although many people emphasize the relatively few conflicts, said Jennifer Orozco, DMSc, PA-C, president and chair of the American Academy of PAs.

“We see that a lot in this country,” she said. “People try to drive a wedge, but it’s often a misnomer that there’s a lot of arguing and infighting.”
 

NPs: Different backgrounds, same goal

The Medscape survey also included information from 750 NPs on working relationships; 93% of them favored nurses and PAs working more independently from doctors.

April Kapu, DNP, ARPN, has worked closely with PAs for more than 20 years. “In my experience ... they complement one another as health team members, although the education and training are somewhat different,” said Ms. Kapu, , president of the American Association of Nurse Practitioners.

Some respondents noted the different educational trajectories for NPs and PAs. “Doctors and PAs are taught using the same model, but NPs are taught under the nursing model,” wrote a family medicine PA.

In emergency departments where Mr. Blumm has worked, ICU NPs have an edge over PAs in terms of preparation, organization, and the tabulation of formulas. On the other hand, some of Mr. Blumm’s fellow PAs were also emergency medicine technicians or respiratory therapists, who had “2 years of classroom training, on par with that of medical students.”

Must these differences in training and education foment conflict between NPs and PAs? “We all bring something different to the table,” said Ms. Kapu, who also is associate dean for clinical and community partnerships at Vanderbilt University, Nashville, Tenn. “It is important to respect each person’s entry point, education, and training.”
 

Differing personalities and environments

Numerous PA respondents said that individual personalities and work environments are more likely to trigger issues with NPs than are differences in training.

“It depends on the team and situation and who the people are, not the letters behind their names,” an emergency medicine PA wrote. A surgical PA noted that “group dynamics and work culture differ from place to place,” while a third PA agreed that “it’s personality dependent, not title dependent.”

No single formula will resolve areas of NP-PA conflict, Ms. Orozco said. “What works in Chicago might not work in rural Colorado or Texas or California, but we do have to come together. The overall focus should be on greater flexibility for PAs and NPs. Patients will fare better.”
 

Joint research, publishing could help

About a decade ago, Mr. Blumm joined with another PA and an NP to form the American College of Clinicians, the first joint PA-NP national professional organization. Although it disbanded after 6 years, owing to low membership, he hopes a similar collaboration will take off in the future.

“I also recommend that PAs and NPs publish articles together, with research as an excellent place to start,” he added. “PAs and NPs should stand together and be a source of healing for all our patients. Regardless of our titles, our responsibility is to bring healing together.”

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

Physician interactions with nurse practitioners (NPs) and physician assistants (PAs) are only going to increase in frequency. – The U.S. Bureau of Labor Statistics forecasts a 40% increase in the NP workforce by 2031, coupled with a 28% rise in PAs.

In recent reports on the quality of the relationships involving these health care professions, survey respondents mostly gave positive accounts of collaboration, using words such as like “comradery,” “teamwork,” “congenial,” and “cohesion.” But all was not perfect. Where and how could these important health care provider relationships improve?
 

PAs: “Competition and collaboration’ with RNs

In a Medscape survey of more than 770 PAs about their working relationships with other health care professionals; 83% of them supported the idea of PAs and NPs practicing more independently from physicians, but sometimes it’s not easy to stay in their individual lanes.

One PA respondent complained that NPs get “more opportunities and preference,” another pointed to PA-NP “turf issues,” and a third griped about NPs’ “strong unions,” which have stoked more fighting about practice abilities and available settings.

Robert Blumm, MA, PA-C, a retired surgical and emergency medicine PA who regards himself as an advocate for both PAs and NPs, describes their interaction as a “mixture of competition and collaboration.”

On one hand, the two groups typically “cooperate and do an excellent job, incurring patient errors similar to or less than physician colleagues or senior residents.” On the other hand, Mr. Blumm conceded, there is some jealousy among PAs over NPs’ advantage in staffing and hiring decisions, “since they don’t need [direct physician] supervision ... and there are limits on how many PAs can be supervised by one physician.”

Most PA-NP interactions are collaborative, although many people emphasize the relatively few conflicts, said Jennifer Orozco, DMSc, PA-C, president and chair of the American Academy of PAs.

“We see that a lot in this country,” she said. “People try to drive a wedge, but it’s often a misnomer that there’s a lot of arguing and infighting.”
 

NPs: Different backgrounds, same goal

The Medscape survey also included information from 750 NPs on working relationships; 93% of them favored nurses and PAs working more independently from doctors.

April Kapu, DNP, ARPN, has worked closely with PAs for more than 20 years. “In my experience ... they complement one another as health team members, although the education and training are somewhat different,” said Ms. Kapu, , president of the American Association of Nurse Practitioners.

Some respondents noted the different educational trajectories for NPs and PAs. “Doctors and PAs are taught using the same model, but NPs are taught under the nursing model,” wrote a family medicine PA.

In emergency departments where Mr. Blumm has worked, ICU NPs have an edge over PAs in terms of preparation, organization, and the tabulation of formulas. On the other hand, some of Mr. Blumm’s fellow PAs were also emergency medicine technicians or respiratory therapists, who had “2 years of classroom training, on par with that of medical students.”

Must these differences in training and education foment conflict between NPs and PAs? “We all bring something different to the table,” said Ms. Kapu, who also is associate dean for clinical and community partnerships at Vanderbilt University, Nashville, Tenn. “It is important to respect each person’s entry point, education, and training.”
 

Differing personalities and environments

Numerous PA respondents said that individual personalities and work environments are more likely to trigger issues with NPs than are differences in training.

“It depends on the team and situation and who the people are, not the letters behind their names,” an emergency medicine PA wrote. A surgical PA noted that “group dynamics and work culture differ from place to place,” while a third PA agreed that “it’s personality dependent, not title dependent.”

No single formula will resolve areas of NP-PA conflict, Ms. Orozco said. “What works in Chicago might not work in rural Colorado or Texas or California, but we do have to come together. The overall focus should be on greater flexibility for PAs and NPs. Patients will fare better.”
 

Joint research, publishing could help

About a decade ago, Mr. Blumm joined with another PA and an NP to form the American College of Clinicians, the first joint PA-NP national professional organization. Although it disbanded after 6 years, owing to low membership, he hopes a similar collaboration will take off in the future.

“I also recommend that PAs and NPs publish articles together, with research as an excellent place to start,” he added. “PAs and NPs should stand together and be a source of healing for all our patients. Regardless of our titles, our responsibility is to bring healing together.”

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.
 

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.
 

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.
 

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.

Waldemarus/iStock/Getty Images Plus

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.

The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.

Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.

The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.

Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.

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

The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.

Waldemarus/iStock/Getty Images Plus

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.

The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.

Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.

The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.

Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.

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

The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.

Waldemarus/iStock/Getty Images Plus

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.

The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.

Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.

The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.

Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.

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

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

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

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

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

Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.

Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liège University, Belgium, and colleagues.

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.

In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti–IL-5 treatment at a single center. The primary outcome was remission of asthma.

Remission was defined as meeting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV₁) of at least 80% predicted; and/or improvement of FEV₁ equal to or larger than 10%, and a blood eosinophil count lower than 300 cells/mL.

Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels in the sputum of each patient.

At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline, compared with those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission, compared with those whose asthma was not in remission (P = .007).

At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein, compared with patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).

Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.

Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti–IL-5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”

The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.

The results suggest that sputum type 2 markers are potential predictors of remission after anti–IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.

The study was supported by GlaxoSmithKline and AstraZeneca. Several coauthors have relationships with these companies. Dr. Moermans has disclosed no relevant financial relationships.

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

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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