Pharmacology

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

Immune checkpoint inhibitor (ICI) therapy does not increase the risk of developing or dying from COVID-19, according to a pair of studies presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.

However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.

In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).

In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).

Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
 

COVID-19 incidence with ICIs

Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.

The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).

In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).

Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.

“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”

COVID-19 mortality with ICIs

For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.

Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.

In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.

Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).

At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.

The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.

“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.

“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
 

ICI therapy can continue, with precautions

“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.

“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.

SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.

“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.

In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.

Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
 

CVD history produced heterogeneity for the primary endpoint

In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.

In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.

“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.

Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”

Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”

In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.

Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.

Finerenone looks better for safety

Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.

mzoler@mdedge.com

Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.

“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.

In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.

Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
 

CVD history produced heterogeneity for the primary endpoint

In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.

In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.

“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.

Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”

Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”

In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.

Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.

Finerenone looks better for safety

Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.

mzoler@mdedge.com

Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist to complete a phase 3 trial, showed cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease, regardless of whether they entered the study with a history of cardiovascular disease, in follow-up analyses of the FIDELIO-DKD trial, which included 5,674 patients.

“Finerenone demonstrated benefits for primary and secondary cardiovascular disease protection,” said Gerasimos Filippatos, MD, at the American Heart Association scientific sessions. Finerenone treatment cut the rate of cardiovascular death, nonfatal MI or stroke, or heart failure hospitalization, when compared with placebo, by a relative 15% among patients with a history of cardiovascular disease (CVD), and by a relative 14% in patients without this history, differences that met a statistical test for consistency. But the absolute, drug-associated increments in benefit over placebo differed between the two CVD subgroups because of a sharp underlying difference in event rates.

In contrast, the analyses reported by Dr. Filippatos and associates from the FIDELIO-DKD study showed significant heterogeneity based on the presence or absence of CVD for the study’s primary endpoint, a composite renal metric that tallied the combined rate of death from renal causes, renal failure, or a sustained drop in estimated glomerular filtration rate of at least 40%. Researchers enrolled patients into FIDELIO-DKD based on having type 2 diabetes (T2D) and chronic kidney disease (CKD). The prevalence of a history of CVD was 46%.

Among patients with a history of CVD, the composite adverse CVD outcome occurred at a rate of 8.5/100 patient-years in patients on placebo and in 7.18/100 patients years among those on finerenone during a median of 2.6 years of follow-up, a 1.32/100–patient-year absolute between-group difference. Among patients in a primary prevention setting, incident CVD event rates during follow-up were roughly half that in the secondary prevention patients. The upshot was that, in the placebo group, the rate was 3.92/100 patient- years, and in those on finerenone was 3.43/100 patient-years, a 0.49/100–patient-year absolute difference.
 

CVD history produced heterogeneity for the primary endpoint

In the analysis that focused on the study’s primary, renal endpoint, among patients identified as having CVD at study entry, the outcome occurred at a rate of 9.06/100 patient-years in the placebo subgroup and at a rate of 6.6/100 patient years in those who received finerenone, a significant 30% relative risk reduction and an absolute between-group difference of 2.46/100 patient-years.

In contrast, among patients without a CVD history, the composite renal endpoint occurred at a rate of 9.1/100 patient-years in the placebo patients and 8.42/100 patient-years in those on finerenone, a 6% relative risk reduction that was not significant, and a 0.68/100–patient-year absolute difference. This disparity in the primary event rate between the two treatment arms reached statistical significance (P = .016), the investigators reported in the published version of the report in Circulation that simultaneously appeared online.

“The totality of evidence suggests that finerenone could be used in patients with T2D with or without a history of CVD,” explained Dr. Filippatos in an interview. “The P-interaction for the composite kidney outcome is significant, but it is not corrected for multiple testing; therefore, it might be a false-chance finding and must be interpreted cautiously.

Furthermore, in another prespecified kidney composite outcome the results were consistent in patients with and without a history of CVD. In sum, all the FIDELIO-DKD analyses so far are “suggestive of a beneficial effect in patients without a history of CVD.”

Despite these patients receiving guideline directed therapies, “there remains a high unmet medical need in patients with T2D and CKD,” added Dr. Filippatos, professor of cardiology at the University of Athens. “We use multiple treatments for patients with heart failure, and we should use the same mindset for treating patients with T2D and CKD. The costs of dialysis and kidney transplant are very high, so it is important to consider options that slow progression of CKD in these patients.”

In FIDELIO-DKD, virtually all patients were on background therapy with a renin-angiotensin-system (RAS) inhibitor, so the trial’s results suggest that treatment should at least involve dual therapy with finerenone and a RAS inhibitor. Fewer than 5% were on background therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a drug class recently established as another key agent for treating CKD in patients with T2D, setting up the prospect for triple therapy, although this approach has not yet undergone prospective testing.

Combining RAS inhibition, finerenone, and an SGLT2 inhibitor is “potentially a marriage made in diabetes heaven,” commented Deepak L. Bhatt, MD, a professor of medicine at Harvard Medical School, Boston, who has not participated in finerenone studies.

Finerenone looks better for safety

Regardless of subgroup analyses based on history of CVD, the findings from all patients enrolled in FIDELIO-DKD were positive for the both the primary renal outcome and key secondary outcome of composite CVD events. In the total randomized cohort, treatment with finerenone on top of optimized treatment with an ACE inhibitor or angiotensin receptor blocker (RAS inhibition) led to a significant 18% relative risk reduction, compared with placebo, for the primary renal endpoint, and a significant 14% relative drop in the key secondary CVD outcome. Those results were published in October in the New England Journal of Medicine.

mzoler@mdedge.com

Early treatment with the antidepressant fluvoxamine (Luvox) may help prevent respiratory deterioration in patients with mild symptomatic COVID-19, results of a preliminary randomized controlled trial suggest.

In the trial, none of the patients who took fluvoxamine within 7 days of first symptoms developed serious breathing difficulties or required hospitalization for respiratory deterioration.

Antiviral effects?

The study included 152 nonhospitalized adults (mean age, 46 years; 72% women) with confirmed SARS-CoV-2 infection and mild COVID-19 symptoms starting within 7 days and oxygen saturation of 92% or greater.

Eighty were randomly assigned to 100 mg of fluvoxamine three times daily for 15 days and 72 to matching placebo.

The primary outcome was clinical deterioration within 15 days of randomization defined by meeting two criteria. These included shortness of breath or hospitalization for shortness of breath or pneumonia and oxygen saturation <92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Clinical deterioration occurred in none of the 80 patients taking fluvoxamine compared with 6 of 72 (8.3%) patients taking placebo, an absolute difference of 8.7% (95% confidence interval, 1.8%-16.4%).

Clinical deterioration in the placebo group happened from 1 to 7 days after randomization and from 3 to 12 days after the onset of COVID-19 symptoms. Four of the 6 patients with clinical deterioration were admitted to the hospital for 4-21 days. One patient required mechanical ventilation for 10 days. No patients died.
 

Hypothesis generating

The authors cautioned that the study was small and with short follow-up and that the findings “need to be interpreted as hypothesis generating rather than as a demonstration of efficacy.”

However, they noted, if the drug turns out to be effective for COVID-19, the potential advantages of fluvoxamine for outpatient use include its safety, widespread availability, low cost, and oral administration.

Carolyn Machamer, PhD, member of the COVID-19 Early Treatment Fund (CETF) scientific advisory board, which funded the study, noted that there are several reasons fluvoxamine might be helpful in COVID-19.

“The preliminary data suggest the mechanism involves activation of the sigma-1 receptor, which has a number of documented activities. One strong possibility is that activation dampens cytokine release and thus the inflammatory response,” she said in an interview.

“Other possible mechanisms can include inhibition of platelet activation and modulation of autophagy. Coronaviruses usurp some autophagy machinery to remodel membranes for replicating their genomes, so this last mechanism might actually be antiviral,” said Dr. Machamer.

She added that a much larger trial is “crucial to see if the initial striking results can be reproduced, and the Healthy Mind Lab and CETF are currently coordinating these next steps.”

The editors of JAMA published an “Editor’s Note” with the study. In it, they wrote the pilot study addresses a “critically important question during the pandemic of how to prevent individuals who acquire COVID-19 from deteriorating to serious illness. If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide.”

However, the study has “important limitations, and the findings should be interpreted as only hypothesis generating; they should not be used as the basis for current treatment decisions,” cautioned authors Christopher Seymour, MD, Howard Bauchner, MD, and Robert Golub, MD.

This study was supported by the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University and the CETF. Additional support was provided by the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation, and the National Institutes of Health.

Dr. Lenze has received grants from the Patient-Centered Outcomes Research Institute, Takeda, Alkermes, Janssen, Acadia, and the Barnes Jewish Hospital Foundation and has received consulting fees from Janssen and Jazz Pharmaceuticals. Dr. Machamer has disclosed no relevant financial relationships. Dr. Seymour has received grants from the National Institutes of Health and personal fees from Beckman Coulter and Edwards Lifesciences.

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

Early treatment with the antidepressant fluvoxamine (Luvox) may help prevent respiratory deterioration in patients with mild symptomatic COVID-19, results of a preliminary randomized controlled trial suggest.

In the trial, none of the patients who took fluvoxamine within 7 days of first symptoms developed serious breathing difficulties or required hospitalization for respiratory deterioration.

Antiviral effects?

The study included 152 nonhospitalized adults (mean age, 46 years; 72% women) with confirmed SARS-CoV-2 infection and mild COVID-19 symptoms starting within 7 days and oxygen saturation of 92% or greater.

Eighty were randomly assigned to 100 mg of fluvoxamine three times daily for 15 days and 72 to matching placebo.

The primary outcome was clinical deterioration within 15 days of randomization defined by meeting two criteria. These included shortness of breath or hospitalization for shortness of breath or pneumonia and oxygen saturation <92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Clinical deterioration occurred in none of the 80 patients taking fluvoxamine compared with 6 of 72 (8.3%) patients taking placebo, an absolute difference of 8.7% (95% confidence interval, 1.8%-16.4%).

Clinical deterioration in the placebo group happened from 1 to 7 days after randomization and from 3 to 12 days after the onset of COVID-19 symptoms. Four of the 6 patients with clinical deterioration were admitted to the hospital for 4-21 days. One patient required mechanical ventilation for 10 days. No patients died.
 

Hypothesis generating

The authors cautioned that the study was small and with short follow-up and that the findings “need to be interpreted as hypothesis generating rather than as a demonstration of efficacy.”

However, they noted, if the drug turns out to be effective for COVID-19, the potential advantages of fluvoxamine for outpatient use include its safety, widespread availability, low cost, and oral administration.

Carolyn Machamer, PhD, member of the COVID-19 Early Treatment Fund (CETF) scientific advisory board, which funded the study, noted that there are several reasons fluvoxamine might be helpful in COVID-19.

“The preliminary data suggest the mechanism involves activation of the sigma-1 receptor, which has a number of documented activities. One strong possibility is that activation dampens cytokine release and thus the inflammatory response,” she said in an interview.

“Other possible mechanisms can include inhibition of platelet activation and modulation of autophagy. Coronaviruses usurp some autophagy machinery to remodel membranes for replicating their genomes, so this last mechanism might actually be antiviral,” said Dr. Machamer.

She added that a much larger trial is “crucial to see if the initial striking results can be reproduced, and the Healthy Mind Lab and CETF are currently coordinating these next steps.”

The editors of JAMA published an “Editor’s Note” with the study. In it, they wrote the pilot study addresses a “critically important question during the pandemic of how to prevent individuals who acquire COVID-19 from deteriorating to serious illness. If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide.”

However, the study has “important limitations, and the findings should be interpreted as only hypothesis generating; they should not be used as the basis for current treatment decisions,” cautioned authors Christopher Seymour, MD, Howard Bauchner, MD, and Robert Golub, MD.

This study was supported by the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University and the CETF. Additional support was provided by the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation, and the National Institutes of Health.

Dr. Lenze has received grants from the Patient-Centered Outcomes Research Institute, Takeda, Alkermes, Janssen, Acadia, and the Barnes Jewish Hospital Foundation and has received consulting fees from Janssen and Jazz Pharmaceuticals. Dr. Machamer has disclosed no relevant financial relationships. Dr. Seymour has received grants from the National Institutes of Health and personal fees from Beckman Coulter and Edwards Lifesciences.

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

Early treatment with the antidepressant fluvoxamine (Luvox) may help prevent respiratory deterioration in patients with mild symptomatic COVID-19, results of a preliminary randomized controlled trial suggest.

In the trial, none of the patients who took fluvoxamine within 7 days of first symptoms developed serious breathing difficulties or required hospitalization for respiratory deterioration.

Antiviral effects?

The study included 152 nonhospitalized adults (mean age, 46 years; 72% women) with confirmed SARS-CoV-2 infection and mild COVID-19 symptoms starting within 7 days and oxygen saturation of 92% or greater.

Eighty were randomly assigned to 100 mg of fluvoxamine three times daily for 15 days and 72 to matching placebo.

The primary outcome was clinical deterioration within 15 days of randomization defined by meeting two criteria. These included shortness of breath or hospitalization for shortness of breath or pneumonia and oxygen saturation <92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Clinical deterioration occurred in none of the 80 patients taking fluvoxamine compared with 6 of 72 (8.3%) patients taking placebo, an absolute difference of 8.7% (95% confidence interval, 1.8%-16.4%).

Clinical deterioration in the placebo group happened from 1 to 7 days after randomization and from 3 to 12 days after the onset of COVID-19 symptoms. Four of the 6 patients with clinical deterioration were admitted to the hospital for 4-21 days. One patient required mechanical ventilation for 10 days. No patients died.
 

Hypothesis generating

The authors cautioned that the study was small and with short follow-up and that the findings “need to be interpreted as hypothesis generating rather than as a demonstration of efficacy.”

However, they noted, if the drug turns out to be effective for COVID-19, the potential advantages of fluvoxamine for outpatient use include its safety, widespread availability, low cost, and oral administration.

Carolyn Machamer, PhD, member of the COVID-19 Early Treatment Fund (CETF) scientific advisory board, which funded the study, noted that there are several reasons fluvoxamine might be helpful in COVID-19.

“The preliminary data suggest the mechanism involves activation of the sigma-1 receptor, which has a number of documented activities. One strong possibility is that activation dampens cytokine release and thus the inflammatory response,” she said in an interview.

“Other possible mechanisms can include inhibition of platelet activation and modulation of autophagy. Coronaviruses usurp some autophagy machinery to remodel membranes for replicating their genomes, so this last mechanism might actually be antiviral,” said Dr. Machamer.

She added that a much larger trial is “crucial to see if the initial striking results can be reproduced, and the Healthy Mind Lab and CETF are currently coordinating these next steps.”

The editors of JAMA published an “Editor’s Note” with the study. In it, they wrote the pilot study addresses a “critically important question during the pandemic of how to prevent individuals who acquire COVID-19 from deteriorating to serious illness. If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide.”

However, the study has “important limitations, and the findings should be interpreted as only hypothesis generating; they should not be used as the basis for current treatment decisions,” cautioned authors Christopher Seymour, MD, Howard Bauchner, MD, and Robert Golub, MD.

This study was supported by the Taylor Family Institute for Innovative Psychiatric Treatment at Washington University and the CETF. Additional support was provided by the Center for Brain Research in Mood Disorders at Washington University, the Bantly Foundation, and the National Institutes of Health.

Dr. Lenze has received grants from the Patient-Centered Outcomes Research Institute, Takeda, Alkermes, Janssen, Acadia, and the Barnes Jewish Hospital Foundation and has received consulting fees from Janssen and Jazz Pharmaceuticals. Dr. Machamer has disclosed no relevant financial relationships. Dr. Seymour has received grants from the National Institutes of Health and personal fees from Beckman Coulter and Edwards Lifesciences.

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

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

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

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

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

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

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

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.