CHEST Physician

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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

Patients with rheumatoid arthritis who carry a specific allele of the gene MUC5B have about double the risk of developing interstitial lung disease when compared with noncarriers, according to a large Finnish biobank study presented at the annual European Congress of Rheumatology.

“The risk difference [or carriers relative to noncarriers] started at about age 65, with a bigger difference [for] men than women,” reported Antti Palomäki, MD, PhD, of the center for rheumatology and clinical immunology at Turku (Finland) University.

The gain-of-function MUC5B variant, which encodes mucin 5B, was first linked to RA-associated interstitial lung disease (ILD) more than 3 years ago. At that time, it was already a known genetic risk factor for idiopathic pulmonary fibrosis in the general population. The new data confirm the association in a longitudinal analysis of a large biobank and suggest the association might have clinical utility.

“This is not ready for clinical practice at the moment. We do not yet know whether we can change therapy to reduce risk,” Dr. Palomäki said, adding “in the future we can look.”

One question that might be asked in clinical studies using MUC5B as a tool to assess and modify risk of ILD in patients with RA is whether one therapy is better than another in avoiding or delaying development of lung fibrosis. Dr. Palomäki noted that biologics, for example, might be a more favorable choice in patients with RA who are at high risk of developing ILD.


The association of the MUC5B variant with increased ILD incidence in patients with RA was drawn from a data set known as FinnGen, a biobank collection of epidemiologic cohorts and hospital samples with genotypes of about 10% of the Finnish population. Follow-up extends to 46 years in some of these individuals.

When 248,4000 individuals in this data set were evaluated, 5,534 had a diagnosis of RA. Of these, 178 (3.2%) developed ILD. About 20% of both those with and without RA were MUC5B variant carriers, meaning the remainder were not.

Sex and age factor into lifetime risk

In patients with RA, the lifetime rate of ILD among MUC5B variant carriers was 16.8% versus only 6.1% among noncarriers. This finding translated into a hazard ratio for ILD of 2.27 (95% confidence interval, 1.75–2.96) for variant carriers versus noncarriers.

The lifetime rate of ILD in patients with RA was greater in men versus women regardless of carrier status (18.5% vs. 8.5%). For women, the lifetime rate was lower for carriers, although the difference relative to female noncarriers was greater (14.5% vs. 4.7%).

ILD, whether in the general population or in patients with RA, is a disease of advancing age. When Dr. Palomäki showed a graph, the rise in ILD incidence did not start in any population, whether those with or without RA and regardless of carrier status, until about age 55. In those without RA and in noncarriers of the variant, ILD incidence remained low and began a discernible climb at around age 70.

In those who did not have RA but were positive for the variant, the rates rose more than twice as fast, particularly after age 70. In people who had RA but not the variant, the rate of ILD was greater than in patients who carried the variant without RA, starting the climb earlier and rising more steeply with age. In those with RA and the variant, the climb in ILD incidence rose rapidly after age 65 years even though the incidence remained fairly similar between all of these groups at age 60.
 

Putting the findings into context

The need to develop ways to prevent ILD in RA is urgent. ILD is one of the most common extraarticular manifestations of RA, developing in up to 60% of patients with RA in older age groups when evaluated with imaging, according to Dr. Palomäki. Although it develops into a clinically significant complication in only about 10% of these patients, ILD still is a significant cause of illness and death in elderly patients with RA.

In the 2018 study that first linked the MUC5B variant to RA-ILD, the investigators also found that the variant was associated with an increased likelihood of developing the usual interstitial pneumonia type of ILD on imaging. David Schwartz, MD, professor of medicine, pulmonary sciences, and critical care and chair of the department of medicine at the University of Colorado at Denver, Aurora, was a senior author of that study. He said these findings build on the 2018 study.

“While the gain-of-function MUC5B promoter variant is important in predicting who will develop RA-ILD, these findings also suggest that MUC5B may be involved in the etiology of RA-ILD, at least for those with the MUC5B variant,” he said.

“The study also raises the possibility that there are several subtypes of RA-ILD, and the subtype that is driven by MUC5B may respond differently to RA biologics or therapeutic agents to treat ILD,” he added.

In the discussion following the presentation by Dr. Palomäki, others agreed, with that statement including Dr. Palomäki. He expressed interest in clinical studies comparing different classes of RA therapies for their relative impact on the risk of developing ILD.Dr. Palomäki reported financial relationships with AbbVie, Merck, Pfizer, and Sanofi. Dr. Schwartz is the founder of Eleven P15, which is developing methods for early diagnosis and treatment of pulmonary fibrosis.

Patients with rheumatoid arthritis who carry a specific allele of the gene MUC5B have about double the risk of developing interstitial lung disease when compared with noncarriers, according to a large Finnish biobank study presented at the annual European Congress of Rheumatology.

“The risk difference [or carriers relative to noncarriers] started at about age 65, with a bigger difference [for] men than women,” reported Antti Palomäki, MD, PhD, of the center for rheumatology and clinical immunology at Turku (Finland) University.

The gain-of-function MUC5B variant, which encodes mucin 5B, was first linked to RA-associated interstitial lung disease (ILD) more than 3 years ago. At that time, it was already a known genetic risk factor for idiopathic pulmonary fibrosis in the general population. The new data confirm the association in a longitudinal analysis of a large biobank and suggest the association might have clinical utility.

“This is not ready for clinical practice at the moment. We do not yet know whether we can change therapy to reduce risk,” Dr. Palomäki said, adding “in the future we can look.”

One question that might be asked in clinical studies using MUC5B as a tool to assess and modify risk of ILD in patients with RA is whether one therapy is better than another in avoiding or delaying development of lung fibrosis. Dr. Palomäki noted that biologics, for example, might be a more favorable choice in patients with RA who are at high risk of developing ILD.


The association of the MUC5B variant with increased ILD incidence in patients with RA was drawn from a data set known as FinnGen, a biobank collection of epidemiologic cohorts and hospital samples with genotypes of about 10% of the Finnish population. Follow-up extends to 46 years in some of these individuals.

When 248,4000 individuals in this data set were evaluated, 5,534 had a diagnosis of RA. Of these, 178 (3.2%) developed ILD. About 20% of both those with and without RA were MUC5B variant carriers, meaning the remainder were not.

Sex and age factor into lifetime risk

In patients with RA, the lifetime rate of ILD among MUC5B variant carriers was 16.8% versus only 6.1% among noncarriers. This finding translated into a hazard ratio for ILD of 2.27 (95% confidence interval, 1.75–2.96) for variant carriers versus noncarriers.

The lifetime rate of ILD in patients with RA was greater in men versus women regardless of carrier status (18.5% vs. 8.5%). For women, the lifetime rate was lower for carriers, although the difference relative to female noncarriers was greater (14.5% vs. 4.7%).

ILD, whether in the general population or in patients with RA, is a disease of advancing age. When Dr. Palomäki showed a graph, the rise in ILD incidence did not start in any population, whether those with or without RA and regardless of carrier status, until about age 55. In those without RA and in noncarriers of the variant, ILD incidence remained low and began a discernible climb at around age 70.

In those who did not have RA but were positive for the variant, the rates rose more than twice as fast, particularly after age 70. In people who had RA but not the variant, the rate of ILD was greater than in patients who carried the variant without RA, starting the climb earlier and rising more steeply with age. In those with RA and the variant, the climb in ILD incidence rose rapidly after age 65 years even though the incidence remained fairly similar between all of these groups at age 60.
 

Putting the findings into context

The need to develop ways to prevent ILD in RA is urgent. ILD is one of the most common extraarticular manifestations of RA, developing in up to 60% of patients with RA in older age groups when evaluated with imaging, according to Dr. Palomäki. Although it develops into a clinically significant complication in only about 10% of these patients, ILD still is a significant cause of illness and death in elderly patients with RA.

In the 2018 study that first linked the MUC5B variant to RA-ILD, the investigators also found that the variant was associated with an increased likelihood of developing the usual interstitial pneumonia type of ILD on imaging. David Schwartz, MD, professor of medicine, pulmonary sciences, and critical care and chair of the department of medicine at the University of Colorado at Denver, Aurora, was a senior author of that study. He said these findings build on the 2018 study.

“While the gain-of-function MUC5B promoter variant is important in predicting who will develop RA-ILD, these findings also suggest that MUC5B may be involved in the etiology of RA-ILD, at least for those with the MUC5B variant,” he said.

“The study also raises the possibility that there are several subtypes of RA-ILD, and the subtype that is driven by MUC5B may respond differently to RA biologics or therapeutic agents to treat ILD,” he added.

In the discussion following the presentation by Dr. Palomäki, others agreed, with that statement including Dr. Palomäki. He expressed interest in clinical studies comparing different classes of RA therapies for their relative impact on the risk of developing ILD.Dr. Palomäki reported financial relationships with AbbVie, Merck, Pfizer, and Sanofi. Dr. Schwartz is the founder of Eleven P15, which is developing methods for early diagnosis and treatment of pulmonary fibrosis.

Patients with rheumatoid arthritis who carry a specific allele of the gene MUC5B have about double the risk of developing interstitial lung disease when compared with noncarriers, according to a large Finnish biobank study presented at the annual European Congress of Rheumatology.

“The risk difference [or carriers relative to noncarriers] started at about age 65, with a bigger difference [for] men than women,” reported Antti Palomäki, MD, PhD, of the center for rheumatology and clinical immunology at Turku (Finland) University.

The gain-of-function MUC5B variant, which encodes mucin 5B, was first linked to RA-associated interstitial lung disease (ILD) more than 3 years ago. At that time, it was already a known genetic risk factor for idiopathic pulmonary fibrosis in the general population. The new data confirm the association in a longitudinal analysis of a large biobank and suggest the association might have clinical utility.

“This is not ready for clinical practice at the moment. We do not yet know whether we can change therapy to reduce risk,” Dr. Palomäki said, adding “in the future we can look.”

One question that might be asked in clinical studies using MUC5B as a tool to assess and modify risk of ILD in patients with RA is whether one therapy is better than another in avoiding or delaying development of lung fibrosis. Dr. Palomäki noted that biologics, for example, might be a more favorable choice in patients with RA who are at high risk of developing ILD.


The association of the MUC5B variant with increased ILD incidence in patients with RA was drawn from a data set known as FinnGen, a biobank collection of epidemiologic cohorts and hospital samples with genotypes of about 10% of the Finnish population. Follow-up extends to 46 years in some of these individuals.

When 248,4000 individuals in this data set were evaluated, 5,534 had a diagnosis of RA. Of these, 178 (3.2%) developed ILD. About 20% of both those with and without RA were MUC5B variant carriers, meaning the remainder were not.

Sex and age factor into lifetime risk

In patients with RA, the lifetime rate of ILD among MUC5B variant carriers was 16.8% versus only 6.1% among noncarriers. This finding translated into a hazard ratio for ILD of 2.27 (95% confidence interval, 1.75–2.96) for variant carriers versus noncarriers.

The lifetime rate of ILD in patients with RA was greater in men versus women regardless of carrier status (18.5% vs. 8.5%). For women, the lifetime rate was lower for carriers, although the difference relative to female noncarriers was greater (14.5% vs. 4.7%).

ILD, whether in the general population or in patients with RA, is a disease of advancing age. When Dr. Palomäki showed a graph, the rise in ILD incidence did not start in any population, whether those with or without RA and regardless of carrier status, until about age 55. In those without RA and in noncarriers of the variant, ILD incidence remained low and began a discernible climb at around age 70.

In those who did not have RA but were positive for the variant, the rates rose more than twice as fast, particularly after age 70. In people who had RA but not the variant, the rate of ILD was greater than in patients who carried the variant without RA, starting the climb earlier and rising more steeply with age. In those with RA and the variant, the climb in ILD incidence rose rapidly after age 65 years even though the incidence remained fairly similar between all of these groups at age 60.
 

Putting the findings into context

The need to develop ways to prevent ILD in RA is urgent. ILD is one of the most common extraarticular manifestations of RA, developing in up to 60% of patients with RA in older age groups when evaluated with imaging, according to Dr. Palomäki. Although it develops into a clinically significant complication in only about 10% of these patients, ILD still is a significant cause of illness and death in elderly patients with RA.

In the 2018 study that first linked the MUC5B variant to RA-ILD, the investigators also found that the variant was associated with an increased likelihood of developing the usual interstitial pneumonia type of ILD on imaging. David Schwartz, MD, professor of medicine, pulmonary sciences, and critical care and chair of the department of medicine at the University of Colorado at Denver, Aurora, was a senior author of that study. He said these findings build on the 2018 study.

“While the gain-of-function MUC5B promoter variant is important in predicting who will develop RA-ILD, these findings also suggest that MUC5B may be involved in the etiology of RA-ILD, at least for those with the MUC5B variant,” he said.

“The study also raises the possibility that there are several subtypes of RA-ILD, and the subtype that is driven by MUC5B may respond differently to RA biologics or therapeutic agents to treat ILD,” he added.

In the discussion following the presentation by Dr. Palomäki, others agreed, with that statement including Dr. Palomäki. He expressed interest in clinical studies comparing different classes of RA therapies for their relative impact on the risk of developing ILD.Dr. Palomäki reported financial relationships with AbbVie, Merck, Pfizer, and Sanofi. Dr. Schwartz is the founder of Eleven P15, which is developing methods for early diagnosis and treatment of pulmonary fibrosis.

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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