PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1–selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti–PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are available at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCLC are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are available at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are available at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on Aug. 25 at Stanford (Calif.) University. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are available at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on Sept. 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are available at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1–selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti–PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are available at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCLC are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are available at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are available at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on Aug. 25 at Stanford (Calif.) University. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are available at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on Sept. 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are available at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1–selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti–PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are available at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCLC are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are available at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are available at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on Aug. 25 at Stanford (Calif.) University. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are available at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on Sept. 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are available at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

I put a Christmas tree up early in November.

It’s not like it’s a real tree, or even a fancy one. For that matter, I’m Jewish.

Growing up in the 1970s one thing that could be relied on every year was the Charlie Brown Christmas special. It never changed. By age 5 you knew most of the lines, and loved the highlight when Charlie Brown brings home the saddest-looking tree ever, which collapses when he puts a single bauble on it.

Courtesy Dr. Allan M. Block

Years ago, my kids gave me a Charlie Brown tree as a gift. It even plays the late Vince Guaraldi’s immortal Peanuts theme when you push a button. I forgot about it for a few years, then discovered it, and immediately brought it to my office.

I’m not a fan of holiday creep, where they move up earlier in the year, so I used to put it up after Thanksgiving. But we close the office 2-3 weeks later for the rest of the year. I like the tree, my staff likes the tree, and my patients like the tree, so I just started putting it up in early November so we can enjoy it for a month.

It’s whimsical and brings back memories of innocence, childhood, and (of course) Peanuts. It sets a cheerful tone when you see it there. Very few of my patients can resist pressing the button and playing the music as they go by.

The start of a new year is a relatively arbitrary date, chosen long ago. But its approach is always a reminder that life goes on. We continue our trips around the sun. Good times and bad times come and go, but time never stops.

In bad years the tree reminds me that it’s coming to an end, and to look toward the next. In good years it reminds me that it’s time to be ready for the surprises of the coming one. With the stresses of the holidays and things (like getting taxes ready) that the year’s end brings, as well as the routine daily challenges of any medical practice, the Charlie Brown Christmas is a reminder to keep a sense of humor.

In mid-December, after the patients are done for the last day of the year, I quietly put it away. It’s a vaguely somber moment, but at the same time I’m glad to know I now have 2-3 weeks of home time. It mostly involves working at my desk and returning phone calls, but there’s also time to relax with my kids, do jigsaw puzzles, and enjoy the Phoenix winter weather as a break before the next round starts.

To those who disagree with my choice of decoration or its timing, I simply respond: “Good grief!”

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I put a Christmas tree up early in November.

It’s not like it’s a real tree, or even a fancy one. For that matter, I’m Jewish.

Growing up in the 1970s one thing that could be relied on every year was the Charlie Brown Christmas special. It never changed. By age 5 you knew most of the lines, and loved the highlight when Charlie Brown brings home the saddest-looking tree ever, which collapses when he puts a single bauble on it.

Courtesy Dr. Allan M. Block

Years ago, my kids gave me a Charlie Brown tree as a gift. It even plays the late Vince Guaraldi’s immortal Peanuts theme when you push a button. I forgot about it for a few years, then discovered it, and immediately brought it to my office.

I’m not a fan of holiday creep, where they move up earlier in the year, so I used to put it up after Thanksgiving. But we close the office 2-3 weeks later for the rest of the year. I like the tree, my staff likes the tree, and my patients like the tree, so I just started putting it up in early November so we can enjoy it for a month.

It’s whimsical and brings back memories of innocence, childhood, and (of course) Peanuts. It sets a cheerful tone when you see it there. Very few of my patients can resist pressing the button and playing the music as they go by.

The start of a new year is a relatively arbitrary date, chosen long ago. But its approach is always a reminder that life goes on. We continue our trips around the sun. Good times and bad times come and go, but time never stops.

In bad years the tree reminds me that it’s coming to an end, and to look toward the next. In good years it reminds me that it’s time to be ready for the surprises of the coming one. With the stresses of the holidays and things (like getting taxes ready) that the year’s end brings, as well as the routine daily challenges of any medical practice, the Charlie Brown Christmas is a reminder to keep a sense of humor.

In mid-December, after the patients are done for the last day of the year, I quietly put it away. It’s a vaguely somber moment, but at the same time I’m glad to know I now have 2-3 weeks of home time. It mostly involves working at my desk and returning phone calls, but there’s also time to relax with my kids, do jigsaw puzzles, and enjoy the Phoenix winter weather as a break before the next round starts.

To those who disagree with my choice of decoration or its timing, I simply respond: “Good grief!”

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I put a Christmas tree up early in November.

It’s not like it’s a real tree, or even a fancy one. For that matter, I’m Jewish.

Growing up in the 1970s one thing that could be relied on every year was the Charlie Brown Christmas special. It never changed. By age 5 you knew most of the lines, and loved the highlight when Charlie Brown brings home the saddest-looking tree ever, which collapses when he puts a single bauble on it.

Courtesy Dr. Allan M. Block

Years ago, my kids gave me a Charlie Brown tree as a gift. It even plays the late Vince Guaraldi’s immortal Peanuts theme when you push a button. I forgot about it for a few years, then discovered it, and immediately brought it to my office.

I’m not a fan of holiday creep, where they move up earlier in the year, so I used to put it up after Thanksgiving. But we close the office 2-3 weeks later for the rest of the year. I like the tree, my staff likes the tree, and my patients like the tree, so I just started putting it up in early November so we can enjoy it for a month.

It’s whimsical and brings back memories of innocence, childhood, and (of course) Peanuts. It sets a cheerful tone when you see it there. Very few of my patients can resist pressing the button and playing the music as they go by.

The start of a new year is a relatively arbitrary date, chosen long ago. But its approach is always a reminder that life goes on. We continue our trips around the sun. Good times and bad times come and go, but time never stops.

In bad years the tree reminds me that it’s coming to an end, and to look toward the next. In good years it reminds me that it’s time to be ready for the surprises of the coming one. With the stresses of the holidays and things (like getting taxes ready) that the year’s end brings, as well as the routine daily challenges of any medical practice, the Charlie Brown Christmas is a reminder to keep a sense of humor.

In mid-December, after the patients are done for the last day of the year, I quietly put it away. It’s a vaguely somber moment, but at the same time I’m glad to know I now have 2-3 weeks of home time. It mostly involves working at my desk and returning phone calls, but there’s also time to relax with my kids, do jigsaw puzzles, and enjoy the Phoenix winter weather as a break before the next round starts.

To those who disagree with my choice of decoration or its timing, I simply respond: “Good grief!”

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.

These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.

Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.

Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.

At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.

To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.

Dr. Pagani noted that these were not “garden-variety” statistical techniques.

“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”

She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.

For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.

“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
 

Seeing TV through a child’s eyes

According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.

“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”

Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.

Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.

“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”

She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.

“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
 

Choosing quality time over screen time

Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.

There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.

If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.

“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”

In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.

“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”

Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.

“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”

Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.

The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.

Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.

These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.

Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.

Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.

At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.

To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.

Dr. Pagani noted that these were not “garden-variety” statistical techniques.

“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”

She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.

For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.

“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
 

Seeing TV through a child’s eyes

According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.

“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”

Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.

Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.

“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”

She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.

“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
 

Choosing quality time over screen time

Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.

There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.

If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.

“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”

In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.

“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”

Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.

“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”

Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.

The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.

Preschoolers who watch violent television are more likely to have emotional and behavioral issues at the age of 12, according to investigators.

These findings align with previous studies that have shown the negative effects of watching violent content, reinforcing the importance of restricting childhood screen time, lead author Linda S. Pagani, PhD, of Université de Montréal and colleagues reported.

Past research measured the immediate or short-term effects of seeing violent media. This study examined how TV violence could be leading to issues almost a decade later, the investigators wrote in the Journal of Developmental & Behavioral Pediatrics.

Their study looked at 1,976 children from the Quebec Longitudinal Study of Child Development, a random representative cohort of boys and girls followed since their births in 1997 and 1998.

At the cohort study follow-ups at ages 3.5 and 4.5 years, the parents of these children reported if their kids watched violent TV, showing that about half of them were exposed. At age 12, the same children were scored by their teachers on a range of psychosocial outcomes, including emotional distress, inattentive behavior, disorderly behavior, social withdrawal, classroom engagement, and overall academic achievement. At this second time point, the children also scored themselves on their own academic motivation and confidence in writing.

To adjust for other factors that could be playing a role, the investigators accounted for participant characteristics at various ages between 5 months and 12 years, as well as differences in parenting styles, home environment, and socioeconomic status.

Dr. Pagani noted that these were not “garden-variety” statistical techniques.

“We did them in such a way that we set ourselves up for not finding results,” Dr. Pagani said in an interview. “That’s why this is really interesting.”

She and her colleagues found that watching TV violence during preschool was significantly associated with multiple negative outcomes at age 12.

For girls, negative outcomes included greater emotional distress, less classroom engagement, lower academic achievement, and less academic motivation. Boys showed greater emotional distress, decreased attention, disorderly behavior, social withdrawal, less classroom engagement, lower academic achievement, and less academic motivation.

“As expected, early screen violence exposure seems to come at a cost,” the investigators wrote.
 

Seeing TV through a child’s eyes

According to Dr. Pagani, many parents think that TV shows watched by preschoolers – like cartoons – are harmless, but these parents need to understand that the brains of children are not yet fully developed.

“The kid has an interpretation that’s very concrete,” Dr. Pagani said. “They don’t have abstract thinking.”

Because of this, kids who see “good guys” beating up “bad guys” don’t understand that the violence is comical and justified; they just see violence being used to address social disagreement, Dr. Pagani said. This leads children to believe that violence is an acceptable way to solve problems in daily life. Children are also more likely to see hostility in others when it isn’t present, leading to conflict.

Although the natural response to these findings is to restrict childhood exposure to violent content, this may be easier said than done, the investigators noted, particularly because TV is no longer the only screen in the home, as it was when this study began. Nowadays, parents need to monitor multiple devices, including smartphones, tablets, and computers, all of which may negatively impact normal brain development.

“People think this technology is innocuous,” Dr. Pagani said. “We are asleep at the wheel.”

She advised parents to wake up and follow the World Health Organization guidelines for sedentary screen time. The guidelines call for no screen time at all until a child is at least 2 years old, and then less than 1 hour per day until age 5.

“It’s the parents who should be in charge,” she said. “They’re the ones who have the cognitive ability to make decisions for their children.”
 

Choosing quality time over screen time

Loredana Marchica, PhD, of Montreal Children’s Hospital and McGill University, also in Montreal, expressed confidence in the study findings, because the results line up with past research, and because the investigators accounted for other explanations.

There is a “very strong probability” that watching violent TV in preschool leads to psychological issues down the line, Dr. Marchica said.

If a child is exposed to violent content, then parents should help children understand the difference between what happens in TV shows and real life, she added, as this can reduce negative effects on behavior.

“Parents need to explain that it’s a TV show,” Dr. Marchica said. “It’s not real, and if [that violent act] happened in real life, it would actually hurt a person.”

In addition to limiting screen time and explaining any violent content, she encouraged parents to spend quality time with their children, especially during the preschool years.

“Those are the years to fortify the attachment you have with that child,” Dr. Marchica said. “Even 15 minutes a day of quality, interactive play time can make such a difference in their development, their imagination, and their social engagement and abilities.”

Parents should also try to have conversations with their young children, she said, noting that it’s okay to share personal feelings, as this teaches kids how to manage their own emotions.

“Not everything is wonderful in life, and we’re allowed to talk about that,” Dr. Marchica said. “[Parents can say,] ‘Mommy had a bad day today. This bad thing happened. But here’s what I did to make myself feel better.’ ”

Dr. Pagani and coauthors termed their findings “robust,” but also cautioned that, in their correlational study, TV violence cannot be interpreted as causal. In other limitations, they noted that the study relies on a single parent-reported item that yielded a low rate of reported exposure. Or the findings could result from other things, such as family chaos or parenting style or something else.

The longitudinal study was supported by Fondation Lucie et André Chagnon, the Institut de la Statistique du Québec, the Ministère de l’Éducation et de l’Enseignement supérieur, and others. The investigators and Dr. Marchica reported no relevant conflicts of interest.

Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.

Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.

Click_and_Photo/Thinkstock

‘An idea whose time has come?’

Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”

The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.

Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.

Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.

As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.

But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”

Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”

Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.

“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
 

What to do with the data?

The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.

Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.  

Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”

He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”

In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”

Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.

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

Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.

Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.

Click_and_Photo/Thinkstock

‘An idea whose time has come?’

Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”

The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.

Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.

Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.

As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.

But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”

Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”

Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.

“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
 

What to do with the data?

The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.

Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.  

Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”

He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”

In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”

Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.

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

Use of continuous glucose monitoring (CGM) by people without diabetes is becoming increasingly popular despite little evidence of benefit thus far, prompting discussion in the diabetes technology community about best practices.

Emerging uses for CGM outside of diabetes include improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivation for healthy behavior change. Such uses are not approved by the Food and Drug Administration and not covered by health insurance, yet a growing number of people are paying digital health companies for the devices as part of wellness packages.

Click_and_Photo/Thinkstock

‘An idea whose time has come?’

Dr. Espinoza was a co-author on a review published online in the Journal of Diabetes Science and Technology, entitled, “Use of Continuous Glucose Monitors by People Without Diabetes: An Idea Whose Time Has Come?”

The review examines several aspects of the issue, beginning with studies that used CGM to investigate glucose concentrations in people with normal fasting glucose and glucose tolerance tests. Nearly all those individuals – from populations around the world – fell in the blood glucose range of 70-140 mg/dL.

Also reviewed are studies using CGM to study effects of diet, exercise, and stress on glucose levels in people without diabetes. Subsequent sections summarize the limited data that are available suggesting potential benefit for use of CGM in metabolic disease including prediabetes and obesity, non-metabolic conditions such as steroid treatment or parenteral nutrition, health and wellness, and among elite athletes. In that last group, glucose levels in both the hypoglycemic and hyperglycemic ranges during intensive activity have been documented.

Currently, there are four CGM devices that are FDA-approved for use in people with diabetes: FreeStyle Libre (Abbott), the implantable Eversense (Senseonics), and devices from Dexcom and Medtronic.

As Dr. Espinoza and colleagues explain in their review, most of the commercial health and wellness CGM programs, such as Nutrisense, Signos, and Supersapiens, actually use sensors made by those same manufacturers. Nutrisense and Supersapiens use the Libre, and Signos uses the Dexcom.

But, rather than the manufacturer’s apps meant for use by people with diabetes, the wellness companies pair the sensors with their own specially designed apps and typically offer additional services such as health coaching or nutrition counseling “to improve general health.”

Subscribers pay a monthly fee. Signos, for example, charges $399 for 1 month, $199/month for 3 months, or $159/month for 6 months. A prescription is required, but the company’s website says, “rest assured, an independent physician will handle the prescription for you, so you won’t need to arrange for a doctor visit. It is included in the cost of membership.”

Several consumer health product companies are now developing non-invasive glucose monitors, most often as a wristwatch, for people without diabetes to measure glucose optically from the skin in the wrist.

“It remains to be determined how accurate these new devices will be and how they will be regulated,” the researchers write.
 

What to do with the data?

The dedicated health and wellness apps typically provide average glucose and trend data but not the GMI. However, in theory users could access that metric by downloading the manufacturers’ viewing apps – for example, Clarity for Dexcom or LibreView for Libre.

Moreover, a person without diabetes could always obtain an off-label prescription from their physician for a FreeStyle Libre and purchase it at a pharmacy. At Walmart, for example, the cost for two boxes of two glucose meters with 14 days of wear each is $136.77. In that situation as well, users could download the viewing app that contains the summary data including the GMI that could potentially mislead in the setting of consistent normoglycemia.  

Dr. Espinoza said: “I think there’s certainly value in glucose levels. We know the summary metrics are useful in type 1 diabetes. We don’t know which summary metrics are going to be useful in any other disease states. We may need brand new summary metrics for other disease states where it’s not about time in range. Maybe the thing that matters is the frequency or height of spikes. We don’t have a measure for that.”

He added that despite the availability of normative data, “even people without diabetes are a fairly heterogenous group. They can still have insulin resistance, so it’s tricky. From a science standpoint, we probably need studies with hundreds of patients with well-established A1c and [insulin resistance measures], weight, and body mass index. Then and only then will we be able to give an accurate glucose profile.”

In the meantime, “more data is always a good thing, but the hard thing is figuring out what do we do with it. Maybe it’s biofeedback for behavioral modification. We don’t know yet. But these are powerful tools and maybe we should learn how to use them better.”

Dr. Shah has reported receiving research grants and participating in advisory boards for Dexcom and Sanofi US. Dr. Espinoza has reported receiving research funding from the National Institutes of Health and FDA.

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

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

As we come to a close on 2022, let’s take a look at the celebrations and frustrations of the past year’s health policies so that they may act as a catalyst, encouraging us to engage with our representatives. Some of these policies include actions by major companies that rule our health care system, as well as the regulations and legislation passed (or not passed) by our governmental entities. And of course, we must consider how profits and politics influence these policies and often rule the roost!

Insurance

Once again, we are facing increased nonmedical switching of stable patients to different medications through ever-increasing formulary exclusions and higher tiering of less profitable drugs. There are some reports of patients being whipsawed back and forth yearly between reference infliximab and various biosimilars, depending on which is the most profitable to the health plan at the time. And now it’s not just the copay accumulator or maximizer programs that are abusing patient assistance programs, there are new “alternative funding companies” that are carving out expensive and specialty drugs from coverage of employers’ funded health plans. These alternative funding companies then obtain medications – sometimes from other countries – and other forms of assistance from manufacturers and foundations. There have been reports that they make the patient assign power of attorney to them and even pretend to be the patient to obtain the drug, assistance, and copay cards and then bill the employer for getting the free drug or assistance. This abuse of the system, along with copay maximizers, are causing drug manufacturers to rethink their assistance policies, with middlemen reaping the advantages of the assistance plans and not the truly needy patient.

Legislation and regulation

Substantive progress continues to be made on access issues in the states. A total of 5 states signed step-therapy legislation into law, 3 states have new copay accumulator program bans, 13 states began to debate the issue of white bagging, and 16 states began to consider the next stage of pharmacy benefit manager (PBM) reform with rebate-pass-through legislation.

At the federal level, the Inflation Reduction Act (IRA; H.R. 5376) was enacted in August and, like all major pieces of legislation, there are pros and cons. On the positive side, the legislation reforms Medicare Part D cost-sharing, including – for the first time – the creation of an annual cap on cost-sharing by beneficiaries. That will especially help patients with high, ongoing prescription drug needs. On the negative side, despite its extensive drug-pricing provisions, the IRA did not include any reform of PBM practices. In fact, Congress has delayed implementation of the so-called “rebate rule” for 10 years. That rule would have essentially ended payments from drug companies to PBMs in exchange for formulary placement by removing safe harbor protection from antikickback law for these payments, allowing patients to benefit from these payments.

Finally, the IRA included extensive provisions applicable to drug manufacturers, including a mechanism for Medicare to set prices directly for medications that have been on the market for a certain number of years but are still without a biosimilar or generic. This will apply fully to selected Part B drugs as of 2028. The key for rheumatologists and our patients in the next few years will be to engage with the Centers for Medicare & Medicaid Services as it implements this provision to ensure that rheumatologists are not underwater financially on the acquisition of medications subject to the new pricing mechanism.

With regard to utilization management reform at the federal level, the Ensuring Seniors’ Timely Access to Care Act (H.R. 3173) would reform prior authorization in Medicare Advantage, but after passing in the House on Sept. 14, the bill has slowed down in the Senate. In some part, that may be because of a surprising score from the Congressional Budget Office, which projected that the bill would cost $16 billion. However, this is not insurmountable: The legislation enjoys broad bipartisan support in the Senate, and its sponsors remain committed to enactment before the end of the year. Additionally, the Safe Step Act (S. 464) would reform step therapy practices in employer-based coverage, but that legislation has not passed either chamber of Congress despite bipartisan support and is unlikely to be enacted before the end of this congressional session.

As noted above, PBMs escaped meaningful scrutiny or reform in the IRA, but the Federal Trade Commission took a different approach when it announced earlier in 2022 that it would conduct an investigation into the business practices of several major PBMs. That study is ongoing and, when finished, will likely result in some additional ideas for meaningful legislative reform.

Finally, there’s the frustration of the egregious Medicare Physician Fee Schedule that has decreased physicians’ reimbursement in a time of accelerated inflation in the cost of running a practice. At the same time, Medicare Advantage plans and everyone else in the government-reimbursed health system are getting at least an inflationary raise. This has created an ire among all physicians that we have not seen in quite a while and which we are leveraging into grassroots outreach.

The problems in the Fee Schedule result from a combination of factors, but one overarching issue is the concept of “budget neutrality,” which essentially requires CMS to make up for any new spending over a certain amount by a commensurate reduction across the whole Fee Schedule. This has the effect of turning the Fee Schedule into a fixed pie: If someone’s slice gets bigger, someone else’s slice must get smaller, but the pie itself never gets bigger. To make matters worse, the Medicare Access and CHIP Reauthorization Act of 2015 has not resulted in advancing value-driven care as the Congress had envisioned when it enacted that legislation. The good news is that there is widespread recognition in Congress that a system built on temporary legislative “patches” to avoid deep payment reductions is unsustainable and must be fixed. The Supporting Medicare Providers Act of 2022 (H.R. 8800) that’s currently pending in the House to offset the looming 2023 Fee Schedule cuts also includes a Sense of the Congress, or nonbinding resolution, establishing the need for administrative and legislative actions for long-term, meaningful reform of Medicare physician payment, along three principles: ensuring financial stability and predictability, promoting and rewarding value-based care innovation, and safeguarding timely access to high-quality care by advancing health equity and reducing disparities.

Turning frustration into action

Much of the frustration for those of us who take care of patients is that many actions and policies are based on profits and politics and not on patient care.

It is unfortunate that money plays such an important role in politics. We are all aware of the power of the well-heeled lobbyist and how money can lead to legislation that is more beneficial to one for-profit company versus another in the health care sector. But then there is the party politics of health care legislation. We see examples of great legislation offered by one party being buried because it might be beneficial to the “other side” in the next election, in spite of the fact that both sides agree on the issue. Here is where we must fight our cynicism and remember our patients. Building and maintaining a relationship with our representatives, whether we agree with them are not, is a very important part of advocacy.

As we come off the recent elections, it is important that we acquaint ourselves with our newly elected representatives and reacquaint ourselves with our re-elected officials. Recently, the Coalition of State Rheumatology Organizations had an advocacy day asking rheumatologists to invite their legislator (city, state, or federal) to their office to witness first-hand the practice of rheumatology. The importance of asking your representative to visit your office cannot be overemphasized. First, you get to know the staffer who arranges these visits. Having a good relationship with your representative’s staff is important in maintaining future communications. Having your legislator tour your office, while you share the daily challenges of getting the right medication for patients, is invaluable to their understanding of how the delay in care that utilization management tools such as prior authorizations and step therapy can cause. It is also helpful for you or your office manager to highlight how independent practices are small businesses that must be run efficiently to ensure they can stay open. Building a relationship with and educating your representatives on issues they may not be familiar with will encourage them to use you as a resource in the future.

CSRO has a legislator invitation template, and we can provide talking points if the invitation is accepted. Many state legislative sessions begin in January, so now is the time to get to know your legislator.

Let’s celebrate the wins of 2022 and not let the frustrations with the system diminish our passion – that’s the hard part! Onward to 2023 as “Rheums for Action!”

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

As we come to a close on 2022, let’s take a look at the celebrations and frustrations of the past year’s health policies so that they may act as a catalyst, encouraging us to engage with our representatives. Some of these policies include actions by major companies that rule our health care system, as well as the regulations and legislation passed (or not passed) by our governmental entities. And of course, we must consider how profits and politics influence these policies and often rule the roost!

Insurance

Once again, we are facing increased nonmedical switching of stable patients to different medications through ever-increasing formulary exclusions and higher tiering of less profitable drugs. There are some reports of patients being whipsawed back and forth yearly between reference infliximab and various biosimilars, depending on which is the most profitable to the health plan at the time. And now it’s not just the copay accumulator or maximizer programs that are abusing patient assistance programs, there are new “alternative funding companies” that are carving out expensive and specialty drugs from coverage of employers’ funded health plans. These alternative funding companies then obtain medications – sometimes from other countries – and other forms of assistance from manufacturers and foundations. There have been reports that they make the patient assign power of attorney to them and even pretend to be the patient to obtain the drug, assistance, and copay cards and then bill the employer for getting the free drug or assistance. This abuse of the system, along with copay maximizers, are causing drug manufacturers to rethink their assistance policies, with middlemen reaping the advantages of the assistance plans and not the truly needy patient.

Legislation and regulation

Substantive progress continues to be made on access issues in the states. A total of 5 states signed step-therapy legislation into law, 3 states have new copay accumulator program bans, 13 states began to debate the issue of white bagging, and 16 states began to consider the next stage of pharmacy benefit manager (PBM) reform with rebate-pass-through legislation.

At the federal level, the Inflation Reduction Act (IRA; H.R. 5376) was enacted in August and, like all major pieces of legislation, there are pros and cons. On the positive side, the legislation reforms Medicare Part D cost-sharing, including – for the first time – the creation of an annual cap on cost-sharing by beneficiaries. That will especially help patients with high, ongoing prescription drug needs. On the negative side, despite its extensive drug-pricing provisions, the IRA did not include any reform of PBM practices. In fact, Congress has delayed implementation of the so-called “rebate rule” for 10 years. That rule would have essentially ended payments from drug companies to PBMs in exchange for formulary placement by removing safe harbor protection from antikickback law for these payments, allowing patients to benefit from these payments.

Finally, the IRA included extensive provisions applicable to drug manufacturers, including a mechanism for Medicare to set prices directly for medications that have been on the market for a certain number of years but are still without a biosimilar or generic. This will apply fully to selected Part B drugs as of 2028. The key for rheumatologists and our patients in the next few years will be to engage with the Centers for Medicare & Medicaid Services as it implements this provision to ensure that rheumatologists are not underwater financially on the acquisition of medications subject to the new pricing mechanism.

With regard to utilization management reform at the federal level, the Ensuring Seniors’ Timely Access to Care Act (H.R. 3173) would reform prior authorization in Medicare Advantage, but after passing in the House on Sept. 14, the bill has slowed down in the Senate. In some part, that may be because of a surprising score from the Congressional Budget Office, which projected that the bill would cost $16 billion. However, this is not insurmountable: The legislation enjoys broad bipartisan support in the Senate, and its sponsors remain committed to enactment before the end of the year. Additionally, the Safe Step Act (S. 464) would reform step therapy practices in employer-based coverage, but that legislation has not passed either chamber of Congress despite bipartisan support and is unlikely to be enacted before the end of this congressional session.

As noted above, PBMs escaped meaningful scrutiny or reform in the IRA, but the Federal Trade Commission took a different approach when it announced earlier in 2022 that it would conduct an investigation into the business practices of several major PBMs. That study is ongoing and, when finished, will likely result in some additional ideas for meaningful legislative reform.

Finally, there’s the frustration of the egregious Medicare Physician Fee Schedule that has decreased physicians’ reimbursement in a time of accelerated inflation in the cost of running a practice. At the same time, Medicare Advantage plans and everyone else in the government-reimbursed health system are getting at least an inflationary raise. This has created an ire among all physicians that we have not seen in quite a while and which we are leveraging into grassroots outreach.

The problems in the Fee Schedule result from a combination of factors, but one overarching issue is the concept of “budget neutrality,” which essentially requires CMS to make up for any new spending over a certain amount by a commensurate reduction across the whole Fee Schedule. This has the effect of turning the Fee Schedule into a fixed pie: If someone’s slice gets bigger, someone else’s slice must get smaller, but the pie itself never gets bigger. To make matters worse, the Medicare Access and CHIP Reauthorization Act of 2015 has not resulted in advancing value-driven care as the Congress had envisioned when it enacted that legislation. The good news is that there is widespread recognition in Congress that a system built on temporary legislative “patches” to avoid deep payment reductions is unsustainable and must be fixed. The Supporting Medicare Providers Act of 2022 (H.R. 8800) that’s currently pending in the House to offset the looming 2023 Fee Schedule cuts also includes a Sense of the Congress, or nonbinding resolution, establishing the need for administrative and legislative actions for long-term, meaningful reform of Medicare physician payment, along three principles: ensuring financial stability and predictability, promoting and rewarding value-based care innovation, and safeguarding timely access to high-quality care by advancing health equity and reducing disparities.

Turning frustration into action

Much of the frustration for those of us who take care of patients is that many actions and policies are based on profits and politics and not on patient care.

It is unfortunate that money plays such an important role in politics. We are all aware of the power of the well-heeled lobbyist and how money can lead to legislation that is more beneficial to one for-profit company versus another in the health care sector. But then there is the party politics of health care legislation. We see examples of great legislation offered by one party being buried because it might be beneficial to the “other side” in the next election, in spite of the fact that both sides agree on the issue. Here is where we must fight our cynicism and remember our patients. Building and maintaining a relationship with our representatives, whether we agree with them are not, is a very important part of advocacy.

As we come off the recent elections, it is important that we acquaint ourselves with our newly elected representatives and reacquaint ourselves with our re-elected officials. Recently, the Coalition of State Rheumatology Organizations had an advocacy day asking rheumatologists to invite their legislator (city, state, or federal) to their office to witness first-hand the practice of rheumatology. The importance of asking your representative to visit your office cannot be overemphasized. First, you get to know the staffer who arranges these visits. Having a good relationship with your representative’s staff is important in maintaining future communications. Having your legislator tour your office, while you share the daily challenges of getting the right medication for patients, is invaluable to their understanding of how the delay in care that utilization management tools such as prior authorizations and step therapy can cause. It is also helpful for you or your office manager to highlight how independent practices are small businesses that must be run efficiently to ensure they can stay open. Building a relationship with and educating your representatives on issues they may not be familiar with will encourage them to use you as a resource in the future.

CSRO has a legislator invitation template, and we can provide talking points if the invitation is accepted. Many state legislative sessions begin in January, so now is the time to get to know your legislator.

Let’s celebrate the wins of 2022 and not let the frustrations with the system diminish our passion – that’s the hard part! Onward to 2023 as “Rheums for Action!”

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

As we come to a close on 2022, let’s take a look at the celebrations and frustrations of the past year’s health policies so that they may act as a catalyst, encouraging us to engage with our representatives. Some of these policies include actions by major companies that rule our health care system, as well as the regulations and legislation passed (or not passed) by our governmental entities. And of course, we must consider how profits and politics influence these policies and often rule the roost!

Insurance

Once again, we are facing increased nonmedical switching of stable patients to different medications through ever-increasing formulary exclusions and higher tiering of less profitable drugs. There are some reports of patients being whipsawed back and forth yearly between reference infliximab and various biosimilars, depending on which is the most profitable to the health plan at the time. And now it’s not just the copay accumulator or maximizer programs that are abusing patient assistance programs, there are new “alternative funding companies” that are carving out expensive and specialty drugs from coverage of employers’ funded health plans. These alternative funding companies then obtain medications – sometimes from other countries – and other forms of assistance from manufacturers and foundations. There have been reports that they make the patient assign power of attorney to them and even pretend to be the patient to obtain the drug, assistance, and copay cards and then bill the employer for getting the free drug or assistance. This abuse of the system, along with copay maximizers, are causing drug manufacturers to rethink their assistance policies, with middlemen reaping the advantages of the assistance plans and not the truly needy patient.

Legislation and regulation

Substantive progress continues to be made on access issues in the states. A total of 5 states signed step-therapy legislation into law, 3 states have new copay accumulator program bans, 13 states began to debate the issue of white bagging, and 16 states began to consider the next stage of pharmacy benefit manager (PBM) reform with rebate-pass-through legislation.

At the federal level, the Inflation Reduction Act (IRA; H.R. 5376) was enacted in August and, like all major pieces of legislation, there are pros and cons. On the positive side, the legislation reforms Medicare Part D cost-sharing, including – for the first time – the creation of an annual cap on cost-sharing by beneficiaries. That will especially help patients with high, ongoing prescription drug needs. On the negative side, despite its extensive drug-pricing provisions, the IRA did not include any reform of PBM practices. In fact, Congress has delayed implementation of the so-called “rebate rule” for 10 years. That rule would have essentially ended payments from drug companies to PBMs in exchange for formulary placement by removing safe harbor protection from antikickback law for these payments, allowing patients to benefit from these payments.

Finally, the IRA included extensive provisions applicable to drug manufacturers, including a mechanism for Medicare to set prices directly for medications that have been on the market for a certain number of years but are still without a biosimilar or generic. This will apply fully to selected Part B drugs as of 2028. The key for rheumatologists and our patients in the next few years will be to engage with the Centers for Medicare & Medicaid Services as it implements this provision to ensure that rheumatologists are not underwater financially on the acquisition of medications subject to the new pricing mechanism.

With regard to utilization management reform at the federal level, the Ensuring Seniors’ Timely Access to Care Act (H.R. 3173) would reform prior authorization in Medicare Advantage, but after passing in the House on Sept. 14, the bill has slowed down in the Senate. In some part, that may be because of a surprising score from the Congressional Budget Office, which projected that the bill would cost $16 billion. However, this is not insurmountable: The legislation enjoys broad bipartisan support in the Senate, and its sponsors remain committed to enactment before the end of the year. Additionally, the Safe Step Act (S. 464) would reform step therapy practices in employer-based coverage, but that legislation has not passed either chamber of Congress despite bipartisan support and is unlikely to be enacted before the end of this congressional session.

As noted above, PBMs escaped meaningful scrutiny or reform in the IRA, but the Federal Trade Commission took a different approach when it announced earlier in 2022 that it would conduct an investigation into the business practices of several major PBMs. That study is ongoing and, when finished, will likely result in some additional ideas for meaningful legislative reform.

Finally, there’s the frustration of the egregious Medicare Physician Fee Schedule that has decreased physicians’ reimbursement in a time of accelerated inflation in the cost of running a practice. At the same time, Medicare Advantage plans and everyone else in the government-reimbursed health system are getting at least an inflationary raise. This has created an ire among all physicians that we have not seen in quite a while and which we are leveraging into grassroots outreach.

The problems in the Fee Schedule result from a combination of factors, but one overarching issue is the concept of “budget neutrality,” which essentially requires CMS to make up for any new spending over a certain amount by a commensurate reduction across the whole Fee Schedule. This has the effect of turning the Fee Schedule into a fixed pie: If someone’s slice gets bigger, someone else’s slice must get smaller, but the pie itself never gets bigger. To make matters worse, the Medicare Access and CHIP Reauthorization Act of 2015 has not resulted in advancing value-driven care as the Congress had envisioned when it enacted that legislation. The good news is that there is widespread recognition in Congress that a system built on temporary legislative “patches” to avoid deep payment reductions is unsustainable and must be fixed. The Supporting Medicare Providers Act of 2022 (H.R. 8800) that’s currently pending in the House to offset the looming 2023 Fee Schedule cuts also includes a Sense of the Congress, or nonbinding resolution, establishing the need for administrative and legislative actions for long-term, meaningful reform of Medicare physician payment, along three principles: ensuring financial stability and predictability, promoting and rewarding value-based care innovation, and safeguarding timely access to high-quality care by advancing health equity and reducing disparities.

Turning frustration into action

Much of the frustration for those of us who take care of patients is that many actions and policies are based on profits and politics and not on patient care.

It is unfortunate that money plays such an important role in politics. We are all aware of the power of the well-heeled lobbyist and how money can lead to legislation that is more beneficial to one for-profit company versus another in the health care sector. But then there is the party politics of health care legislation. We see examples of great legislation offered by one party being buried because it might be beneficial to the “other side” in the next election, in spite of the fact that both sides agree on the issue. Here is where we must fight our cynicism and remember our patients. Building and maintaining a relationship with our representatives, whether we agree with them are not, is a very important part of advocacy.

As we come off the recent elections, it is important that we acquaint ourselves with our newly elected representatives and reacquaint ourselves with our re-elected officials. Recently, the Coalition of State Rheumatology Organizations had an advocacy day asking rheumatologists to invite their legislator (city, state, or federal) to their office to witness first-hand the practice of rheumatology. The importance of asking your representative to visit your office cannot be overemphasized. First, you get to know the staffer who arranges these visits. Having a good relationship with your representative’s staff is important in maintaining future communications. Having your legislator tour your office, while you share the daily challenges of getting the right medication for patients, is invaluable to their understanding of how the delay in care that utilization management tools such as prior authorizations and step therapy can cause. It is also helpful for you or your office manager to highlight how independent practices are small businesses that must be run efficiently to ensure they can stay open. Building a relationship with and educating your representatives on issues they may not be familiar with will encourage them to use you as a resource in the future.

CSRO has a legislator invitation template, and we can provide talking points if the invitation is accepted. Many state legislative sessions begin in January, so now is the time to get to know your legislator.

Let’s celebrate the wins of 2022 and not let the frustrations with the system diminish our passion – that’s the hard part! Onward to 2023 as “Rheums for Action!”

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.