Bone fractures more likely to occur in psoriasis, PsA patients

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Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

Dr. Alexis R. Ogdie-Beatty
Dr. Ogdie-Beatty and her coinvestigators conducted a longitudinal, population-based study involving patients with PsA and psoriasis, comparing incidences of bone fractures in those patients against patients with rheumatoid arthritis (RA) and the general population, which served as the control group. All patients screened for eligibility were between the ages of 18 and 89 years, with data collected from the Health Improvement Network of the United Kingdom from 1994 through January 2014.

A total of 9,788 PsA and 158,323 psoriasis patients were included in the study, along with 39,306 RA patients and 821,834 individuals from the general population. Psoriasis patients were divided into groups classified as mild (n = 149,809) or severe (n = 8,514). The average age of each cohort ranged from nearly 47 years to almost 59 years, with all cohorts comprising mostly females, ranging from about 51% to 69%.

“We found that the risk for any fracture in patients with PsA and severe psoriasis was similar to RA [but] patients with PsA and psoriasis had an increased incidence of fracture compared with the general population by 7%-26%,” the authors explained. “The incidence of vertebral fracture was also increased in patients with severe psoriasis and while hip fracture was elevated in both psoriasis groups, it was only statistically significant in patients with mild psoriasis relative to matched controls after adjusting for risk factors for osteoporosis.”

Dr. Ogdie-Beatty and her colleagues found that all of the conditions conferred an elevated risk for fractures anywhere in the body when compared with the general population, reaching hazard ratios of 1.16 (95% confidence interval, 1.06-1.27) for people with PsA, 1.07 (95% CI, 1.05-1.10) for mild psoriasis, 1.26 for severe psoriasis (95% CI, 1.15-1.39), and 1.23 for RA (95% CI, 1.18-1.28). The risk for hip fractures was only significantly higher for mild (hazard ratio, 1.13; 95% CI, 1.04-1.22) and severe psoriasis (HR, 1.21; 95% CI, 0.88-1.66), and RA (HR, 1.55; 95% CI, 1.40-1.72). Individuals with PsA did not have a significantly higher risk for vertebral fractures (HR, 1.07; 95% CI, 0.66-1.72), whereas those with mild psoriasis (HR, 1.17; 95% CI, 1.03-1.33), severe psoriasis (HR, 2.23; 95% CI, 1.54-3.22), or RA did (HR, 1.53; 95% CI, 1.30-1.80). Each of these models were fully adjusted for multiple different osteoporosis risk factors, although they were all commonly adjusted for age, sex, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, stroke, SSRI use, tricyclic antidepressant use, oral steroids, smoking, and categorical body mass index.

Individual coauthors disclosed receiving funding for their work from the National Institutes of Health, as well as grants from the Department of Veterans Affairs and the Rheumatology Research Foundation. Three of the authors reported receiving payment for continuing medical education work related to psoriatic arthritis or psoriasis.
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Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

Dr. Alexis R. Ogdie-Beatty
Dr. Ogdie-Beatty and her coinvestigators conducted a longitudinal, population-based study involving patients with PsA and psoriasis, comparing incidences of bone fractures in those patients against patients with rheumatoid arthritis (RA) and the general population, which served as the control group. All patients screened for eligibility were between the ages of 18 and 89 years, with data collected from the Health Improvement Network of the United Kingdom from 1994 through January 2014.

A total of 9,788 PsA and 158,323 psoriasis patients were included in the study, along with 39,306 RA patients and 821,834 individuals from the general population. Psoriasis patients were divided into groups classified as mild (n = 149,809) or severe (n = 8,514). The average age of each cohort ranged from nearly 47 years to almost 59 years, with all cohorts comprising mostly females, ranging from about 51% to 69%.

“We found that the risk for any fracture in patients with PsA and severe psoriasis was similar to RA [but] patients with PsA and psoriasis had an increased incidence of fracture compared with the general population by 7%-26%,” the authors explained. “The incidence of vertebral fracture was also increased in patients with severe psoriasis and while hip fracture was elevated in both psoriasis groups, it was only statistically significant in patients with mild psoriasis relative to matched controls after adjusting for risk factors for osteoporosis.”

Dr. Ogdie-Beatty and her colleagues found that all of the conditions conferred an elevated risk for fractures anywhere in the body when compared with the general population, reaching hazard ratios of 1.16 (95% confidence interval, 1.06-1.27) for people with PsA, 1.07 (95% CI, 1.05-1.10) for mild psoriasis, 1.26 for severe psoriasis (95% CI, 1.15-1.39), and 1.23 for RA (95% CI, 1.18-1.28). The risk for hip fractures was only significantly higher for mild (hazard ratio, 1.13; 95% CI, 1.04-1.22) and severe psoriasis (HR, 1.21; 95% CI, 0.88-1.66), and RA (HR, 1.55; 95% CI, 1.40-1.72). Individuals with PsA did not have a significantly higher risk for vertebral fractures (HR, 1.07; 95% CI, 0.66-1.72), whereas those with mild psoriasis (HR, 1.17; 95% CI, 1.03-1.33), severe psoriasis (HR, 2.23; 95% CI, 1.54-3.22), or RA did (HR, 1.53; 95% CI, 1.30-1.80). Each of these models were fully adjusted for multiple different osteoporosis risk factors, although they were all commonly adjusted for age, sex, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, stroke, SSRI use, tricyclic antidepressant use, oral steroids, smoking, and categorical body mass index.

Individual coauthors disclosed receiving funding for their work from the National Institutes of Health, as well as grants from the Department of Veterans Affairs and the Rheumatology Research Foundation. Three of the authors reported receiving payment for continuing medical education work related to psoriatic arthritis or psoriasis.

 

Individuals who have psoriasis or psoriatic arthritis are at a significantly higher risk of also suffering bone fractures, particularly in their hip and vertebrae, according to a new study published in the Annals of the Rheumatic Diseases.

“To our knowledge, these are the first population-based estimates of the risk for incident fracture and osteoporosis in patients with psoriasis and/or PsA [psoriatic arthritis] and the first longitudinal cohort study to address this issue,” wrote the authors of the study, led by Alexis Ogdie-Beatty, MD, of the University of Pennsylvania in Philadelphia (Ann Rheum Dis. 2017 Jan 16. doi: 10.1136/annrheumdis-2016-210441).

Dr. Alexis R. Ogdie-Beatty
Dr. Ogdie-Beatty and her coinvestigators conducted a longitudinal, population-based study involving patients with PsA and psoriasis, comparing incidences of bone fractures in those patients against patients with rheumatoid arthritis (RA) and the general population, which served as the control group. All patients screened for eligibility were between the ages of 18 and 89 years, with data collected from the Health Improvement Network of the United Kingdom from 1994 through January 2014.

A total of 9,788 PsA and 158,323 psoriasis patients were included in the study, along with 39,306 RA patients and 821,834 individuals from the general population. Psoriasis patients were divided into groups classified as mild (n = 149,809) or severe (n = 8,514). The average age of each cohort ranged from nearly 47 years to almost 59 years, with all cohorts comprising mostly females, ranging from about 51% to 69%.

“We found that the risk for any fracture in patients with PsA and severe psoriasis was similar to RA [but] patients with PsA and psoriasis had an increased incidence of fracture compared with the general population by 7%-26%,” the authors explained. “The incidence of vertebral fracture was also increased in patients with severe psoriasis and while hip fracture was elevated in both psoriasis groups, it was only statistically significant in patients with mild psoriasis relative to matched controls after adjusting for risk factors for osteoporosis.”

Dr. Ogdie-Beatty and her colleagues found that all of the conditions conferred an elevated risk for fractures anywhere in the body when compared with the general population, reaching hazard ratios of 1.16 (95% confidence interval, 1.06-1.27) for people with PsA, 1.07 (95% CI, 1.05-1.10) for mild psoriasis, 1.26 for severe psoriasis (95% CI, 1.15-1.39), and 1.23 for RA (95% CI, 1.18-1.28). The risk for hip fractures was only significantly higher for mild (hazard ratio, 1.13; 95% CI, 1.04-1.22) and severe psoriasis (HR, 1.21; 95% CI, 0.88-1.66), and RA (HR, 1.55; 95% CI, 1.40-1.72). Individuals with PsA did not have a significantly higher risk for vertebral fractures (HR, 1.07; 95% CI, 0.66-1.72), whereas those with mild psoriasis (HR, 1.17; 95% CI, 1.03-1.33), severe psoriasis (HR, 2.23; 95% CI, 1.54-3.22), or RA did (HR, 1.53; 95% CI, 1.30-1.80). Each of these models were fully adjusted for multiple different osteoporosis risk factors, although they were all commonly adjusted for age, sex, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, stroke, SSRI use, tricyclic antidepressant use, oral steroids, smoking, and categorical body mass index.

Individual coauthors disclosed receiving funding for their work from the National Institutes of Health, as well as grants from the Department of Veterans Affairs and the Rheumatology Research Foundation. Three of the authors reported receiving payment for continuing medical education work related to psoriatic arthritis or psoriasis.
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Key clinical point: Psoriasis and psoriatic arthritis significantly increase the risk of bone fractures.

Major finding: The risk of fracture for patients with PsA and psoriasis had a risk of fracture that was increased by 7%-26% in comparison with the general U.K. population.

Data source: Population-based, longitudinal cohort study of 9,788 PsA patients and 158,323 psoriasis patients in the United Kingdom during 1994-2014.

Disclosures: Individual coauthors disclosed receiving funding for their work from the National Institutes of Health, as well as grants from the Department of Veterans Affairs and the Rheumatology Research Foundation. Three of the authors reported receiving payment for continuing medical education work related to psoriatic arthritis or psoriasis.

Nivolumab effective in PD-L1–deficient lung cancers

Further optimization of immunotherapy needed
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– The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.

“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

Mitchel L. Zoler/Frontline Medical News
Dr. Solange Peters
As a result, nivolumab (Opdivo) is now the standard of care for second-line treatment of advanced squamous or nonsquamous non–small cell lung cancer (NSCLC) regardless of the tumor’s expression of programmed death–1 ligand (PD-1L), said Dr. Peters, a thoracic oncologist at the University of Lausanne (Switzerland). The 2015 Food and Drug Administration approval cited results from the Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic NSCLC (CheckMate057) trial. Those results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen (New Engl J Med. 2015 Oct. 22;373[17]:1627-39).

But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.

A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.

Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.

In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.

CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
 
Body

 

The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.

In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.

Mitchel L. Zoler/Frontline Medical News
Dr. Paul Mitchell
Immunotherapy must become better optimized. The majority of patients treated with immunotherapy today do not receive substantial benefit. We need to address these patients with new treatment strategies. We currently do not know the optimal duration of initial immunotherapy treatment, or whether subsequent treatment with the same or a different agent will provide additional benefit to patients.

The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.

Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
 

Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.

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The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.

In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.

Mitchel L. Zoler/Frontline Medical News
Dr. Paul Mitchell
Immunotherapy must become better optimized. The majority of patients treated with immunotherapy today do not receive substantial benefit. We need to address these patients with new treatment strategies. We currently do not know the optimal duration of initial immunotherapy treatment, or whether subsequent treatment with the same or a different agent will provide additional benefit to patients.

The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.

Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
 

Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.

Body

 

The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.

In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.

Mitchel L. Zoler/Frontline Medical News
Dr. Paul Mitchell
Immunotherapy must become better optimized. The majority of patients treated with immunotherapy today do not receive substantial benefit. We need to address these patients with new treatment strategies. We currently do not know the optimal duration of initial immunotherapy treatment, or whether subsequent treatment with the same or a different agent will provide additional benefit to patients.

The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.

Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
 

Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.

Title
Further optimization of immunotherapy needed
Further optimization of immunotherapy needed

 

– The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.

“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

Mitchel L. Zoler/Frontline Medical News
Dr. Solange Peters
As a result, nivolumab (Opdivo) is now the standard of care for second-line treatment of advanced squamous or nonsquamous non–small cell lung cancer (NSCLC) regardless of the tumor’s expression of programmed death–1 ligand (PD-1L), said Dr. Peters, a thoracic oncologist at the University of Lausanne (Switzerland). The 2015 Food and Drug Administration approval cited results from the Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic NSCLC (CheckMate057) trial. Those results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen (New Engl J Med. 2015 Oct. 22;373[17]:1627-39).

But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.

A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.

Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.

In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.

CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
 

 

– The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.

“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

Mitchel L. Zoler/Frontline Medical News
Dr. Solange Peters
As a result, nivolumab (Opdivo) is now the standard of care for second-line treatment of advanced squamous or nonsquamous non–small cell lung cancer (NSCLC) regardless of the tumor’s expression of programmed death–1 ligand (PD-1L), said Dr. Peters, a thoracic oncologist at the University of Lausanne (Switzerland). The 2015 Food and Drug Administration approval cited results from the Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic NSCLC (CheckMate057) trial. Those results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen (New Engl J Med. 2015 Oct. 22;373[17]:1627-39).

But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.

A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.

Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.

In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.

CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
 
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Key clinical point: A detailed analysis of nivolumab’s performance in a pivotal trial with non–small cell lung cancer patients showed similar efficacy to docetaxel for tumors with no or very low PD-L1 expression and superior efficacy for tumors with higher levels of PD-L1.

Major finding: When tumors had at least 1% PD-L1 expression, objective response rates were 31% with nivolumab and 12% with docetaxel.

Data source: CheckMate057, a pivotal trial of nivolumab that enrolled 592 patients with advanced, nonsquamous non–small cell lung cancer.

Disclosures: CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.

Vagus Nerve Stimulation Reduces Seizures and Improves Quality of Life

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Patients with epilepsy saw improvements in alertness, mood, and verbal communication.

Patients with epilepsy who do not respond to drug therapy and who are not candidates for surgery sometimes respond to vagus nerve stimulation (VNS). Research suggests that VNS reduces the frequency of seizures, but a recent study now suggests it may also improve patients’ quality of life. Englot et al found that the therapy improves alertness, post-ictal state, cluster seizures, mood, verbal communication, school and professional achievements, and memory. Several factors predicted patients’ improvement, including a shorter time to implant, female gender, generalized seizure type, and being Caucasian.

Englot DJ, Hassnain KH, Rolston JD, et al. Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data. Epilepsy Behav. 2017;66:4-9.

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Patients with epilepsy saw improvements in alertness, mood, and verbal communication.
Patients with epilepsy saw improvements in alertness, mood, and verbal communication.

Patients with epilepsy who do not respond to drug therapy and who are not candidates for surgery sometimes respond to vagus nerve stimulation (VNS). Research suggests that VNS reduces the frequency of seizures, but a recent study now suggests it may also improve patients’ quality of life. Englot et al found that the therapy improves alertness, post-ictal state, cluster seizures, mood, verbal communication, school and professional achievements, and memory. Several factors predicted patients’ improvement, including a shorter time to implant, female gender, generalized seizure type, and being Caucasian.

Englot DJ, Hassnain KH, Rolston JD, et al. Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data. Epilepsy Behav. 2017;66:4-9.

Patients with epilepsy who do not respond to drug therapy and who are not candidates for surgery sometimes respond to vagus nerve stimulation (VNS). Research suggests that VNS reduces the frequency of seizures, but a recent study now suggests it may also improve patients’ quality of life. Englot et al found that the therapy improves alertness, post-ictal state, cluster seizures, mood, verbal communication, school and professional achievements, and memory. Several factors predicted patients’ improvement, including a shorter time to implant, female gender, generalized seizure type, and being Caucasian.

Englot DJ, Hassnain KH, Rolston JD, et al. Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data. Epilepsy Behav. 2017;66:4-9.

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Auditory Auras May Signal Poor Surgical Outcomes

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Drug-resistant patients with temporal lobe epilepsy and auras had a poorer prognosis.

Patients with temporal lobe epilepsy are more likely to fare poorly after surgery if they experience auditory auras. When Ali A. Asadi-Pooya and associates performed a retrospective analysis of 1186 drug-resistant patients who had had a temporal resection, they found that those with auditory auras were more likely to relapse after surgery, when compared to those who did not experience the auras (P=.03). The side of the head in which the procedure was performed did not affect postoperative prognosis.

Asadi-Pooya AA, Wyeth D, Nei M, et al. Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy. Epilepsy Behav. 2017;66:49-52.

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Drug-resistant patients with temporal lobe epilepsy and auras had a poorer prognosis.
Drug-resistant patients with temporal lobe epilepsy and auras had a poorer prognosis.

Patients with temporal lobe epilepsy are more likely to fare poorly after surgery if they experience auditory auras. When Ali A. Asadi-Pooya and associates performed a retrospective analysis of 1186 drug-resistant patients who had had a temporal resection, they found that those with auditory auras were more likely to relapse after surgery, when compared to those who did not experience the auras (P=.03). The side of the head in which the procedure was performed did not affect postoperative prognosis.

Asadi-Pooya AA, Wyeth D, Nei M, et al. Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy. Epilepsy Behav. 2017;66:49-52.

Patients with temporal lobe epilepsy are more likely to fare poorly after surgery if they experience auditory auras. When Ali A. Asadi-Pooya and associates performed a retrospective analysis of 1186 drug-resistant patients who had had a temporal resection, they found that those with auditory auras were more likely to relapse after surgery, when compared to those who did not experience the auras (P=.03). The side of the head in which the procedure was performed did not affect postoperative prognosis.

Asadi-Pooya AA, Wyeth D, Nei M, et al. Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy. Epilepsy Behav. 2017;66:49-52.

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Older, Poorer Patients With Epilepsy Less Likely to Take their Medication

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Researchers also found that minority patients were less adherent.

Approximately one-third of older adults with epilepsy do not adhere very well to their antiepileptic drug regimen, with older minority patients even less compliant. That’s the conclusion reached by researchers who analyzed Medicare claims from 2008 to 2010, using a 5% random sample of beneficiaries and augmenting it with minority patients. Piper et al looked at 36,912 cases of epilepsy and found 31.8% were nonadherent; that included 24.1% of whites and 34.3% of African Americans. They also found that Medicare beneficiaries who lived in high poverty areas were more likely to be noncompliant.

Piper K, Richman J, Faught E, at al. Adherence to antiepileptic drugs among diverse older Americans on Part D Medicare.  Epilepsy Behav. 2017;66:68-73.

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Researchers also found that minority patients were less adherent.
Researchers also found that minority patients were less adherent.

Approximately one-third of older adults with epilepsy do not adhere very well to their antiepileptic drug regimen, with older minority patients even less compliant. That’s the conclusion reached by researchers who analyzed Medicare claims from 2008 to 2010, using a 5% random sample of beneficiaries and augmenting it with minority patients. Piper et al looked at 36,912 cases of epilepsy and found 31.8% were nonadherent; that included 24.1% of whites and 34.3% of African Americans. They also found that Medicare beneficiaries who lived in high poverty areas were more likely to be noncompliant.

Piper K, Richman J, Faught E, at al. Adherence to antiepileptic drugs among diverse older Americans on Part D Medicare.  Epilepsy Behav. 2017;66:68-73.

Approximately one-third of older adults with epilepsy do not adhere very well to their antiepileptic drug regimen, with older minority patients even less compliant. That’s the conclusion reached by researchers who analyzed Medicare claims from 2008 to 2010, using a 5% random sample of beneficiaries and augmenting it with minority patients. Piper et al looked at 36,912 cases of epilepsy and found 31.8% were nonadherent; that included 24.1% of whites and 34.3% of African Americans. They also found that Medicare beneficiaries who lived in high poverty areas were more likely to be noncompliant.

Piper K, Richman J, Faught E, at al. Adherence to antiepileptic drugs among diverse older Americans on Part D Medicare.  Epilepsy Behav. 2017;66:68-73.

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Senate takes first step toward repealing ACA

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With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act.

Republican Senators will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage.

The budget resolution contains no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

Sen. Lamar Alexander (R-Tenn.)
However, in a floor speech Jan. 11, Sen. Lamar Alexander (R-Tenn.), chairman of the U.S. Senate Committee on Health, Education, Labor, and Pensions, offered some nuggets on how repeal-and-replace would proceed.

Senate Republicans “plan to rescue those trapped in a failing system, to replace that system with a functional market, or markets, and then repeal Obamacare for good,” he said.

Sen. Alexander said the process will come in three parts. The first will protect the 11 million people who have purchased health insurance through the exchanges so that they don’t lose coverage.

“Second, we will build better systems providing Americans with more choices that cost less,” he said. “Note I say systems, not one system. If anyone is expecting [Senate Majority Leader Mitch] McConnell [R-Ky.] to roll a wheelbarrow on the Senate floor with a comprehensive Republican health care plan, they’re going to be waiting a long time because we don’t believe in that. We don’t want to replace a failed Obamacare federal system with another failed federal system.”

The last part will be to repeal what remains of the law after the new plan is in place.

Sen. Alexander reiterated that any future bill will keep the ban on coverage denials for preexisting conditions and the allowance of coverage of children up to the age of 26 who are on their parents’ plans.

He stated that this reform effort will not address Medicare reform, which will be the subject of separate legislative action.

The AGA opposes repealing the ACA unless a viable, equitable replacement is in place. Patients who have received coverage through the ACA should be able to maintain coverage without interruption, and any replacement package must ensure patient access and coverage of specialty care, provide for preventive screenings without cost-sharing, not discriminate on the basis of a pre-existing condition or gender, cover children until they are age 26, and ban annual and lifetime caps on coverage.
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With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act.

Republican Senators will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage.

The budget resolution contains no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

Sen. Lamar Alexander (R-Tenn.)
However, in a floor speech Jan. 11, Sen. Lamar Alexander (R-Tenn.), chairman of the U.S. Senate Committee on Health, Education, Labor, and Pensions, offered some nuggets on how repeal-and-replace would proceed.

Senate Republicans “plan to rescue those trapped in a failing system, to replace that system with a functional market, or markets, and then repeal Obamacare for good,” he said.

Sen. Alexander said the process will come in three parts. The first will protect the 11 million people who have purchased health insurance through the exchanges so that they don’t lose coverage.

“Second, we will build better systems providing Americans with more choices that cost less,” he said. “Note I say systems, not one system. If anyone is expecting [Senate Majority Leader Mitch] McConnell [R-Ky.] to roll a wheelbarrow on the Senate floor with a comprehensive Republican health care plan, they’re going to be waiting a long time because we don’t believe in that. We don’t want to replace a failed Obamacare federal system with another failed federal system.”

The last part will be to repeal what remains of the law after the new plan is in place.

Sen. Alexander reiterated that any future bill will keep the ban on coverage denials for preexisting conditions and the allowance of coverage of children up to the age of 26 who are on their parents’ plans.

He stated that this reform effort will not address Medicare reform, which will be the subject of separate legislative action.

The AGA opposes repealing the ACA unless a viable, equitable replacement is in place. Patients who have received coverage through the ACA should be able to maintain coverage without interruption, and any replacement package must ensure patient access and coverage of specialty care, provide for preventive screenings without cost-sharing, not discriminate on the basis of a pre-existing condition or gender, cover children until they are age 26, and ban annual and lifetime caps on coverage.


With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act.

Republican Senators will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage.

The budget resolution contains no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

Sen. Lamar Alexander (R-Tenn.)
However, in a floor speech Jan. 11, Sen. Lamar Alexander (R-Tenn.), chairman of the U.S. Senate Committee on Health, Education, Labor, and Pensions, offered some nuggets on how repeal-and-replace would proceed.

Senate Republicans “plan to rescue those trapped in a failing system, to replace that system with a functional market, or markets, and then repeal Obamacare for good,” he said.

Sen. Alexander said the process will come in three parts. The first will protect the 11 million people who have purchased health insurance through the exchanges so that they don’t lose coverage.

“Second, we will build better systems providing Americans with more choices that cost less,” he said. “Note I say systems, not one system. If anyone is expecting [Senate Majority Leader Mitch] McConnell [R-Ky.] to roll a wheelbarrow on the Senate floor with a comprehensive Republican health care plan, they’re going to be waiting a long time because we don’t believe in that. We don’t want to replace a failed Obamacare federal system with another failed federal system.”

The last part will be to repeal what remains of the law after the new plan is in place.

Sen. Alexander reiterated that any future bill will keep the ban on coverage denials for preexisting conditions and the allowance of coverage of children up to the age of 26 who are on their parents’ plans.

He stated that this reform effort will not address Medicare reform, which will be the subject of separate legislative action.

The AGA opposes repealing the ACA unless a viable, equitable replacement is in place. Patients who have received coverage through the ACA should be able to maintain coverage without interruption, and any replacement package must ensure patient access and coverage of specialty care, provide for preventive screenings without cost-sharing, not discriminate on the basis of a pre-existing condition or gender, cover children until they are age 26, and ban annual and lifetime caps on coverage.
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CMS nixes Part B drug payment demonstration

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A controversial demonstration project that would have tested new methods to pay for the drugs administered in medical offices has been canceled by the Centers for Medicare & Medicaid Services. The agency received considerable backlash from physicians, Congress, and others when the demonstration project was announced in March 2016.

anttohoho/Thinkstock
“After considering comments, CMS will not finalize the Medicare Part B Drug Payment Model during this administration,” the agency said in a statement. “The proposal was intended to test whether alternative drug payment structures would improve the quality of patient care and the value of Medicare drug spending.”

The agency said it received “a great deal of support from some” for the proposed demonstration. However, “a number of stakeholders expressed strong concerns about the model. While CMS was working to address these concerns, the complexity of the issues and the limited time available led to the decision not to finalize the rule at this time.”

The demonstration project was designed to test new methods to “improve how Medicare Part B pays for prescription drugs and supports physicians and other clinicians in delivering high quality care,” according to a fact sheet published in March.

Under the project, medical practices would have been divided into two groups. A control group would continue to be paid for Part B drugs at the current rate of 106% of average sales price (ASP), while the other would have been paid at 102.5% of ASP plus a flat fee of $16.80 per drug payment. Starting in January 2017, each group would have been further subdivided with a portion of each being subjected to value-based purchasing tools.

One key criticism of the demonstration project centered on the proposed randomization of practices, which was based on primary care service areas (clusters of zip codes with similar Part B medical care patterns). That randomization scheme could have caused different payment levels – and patient out-of-pocket spending – for geographically close areas. Further, participation in the demonstration project would have been mandatory, with no mechanism to opt out.

“This is a model for how Washington should, but often doesn’t, work,” American Medical Association President Andrew W. Gurman, MD, said in a statement. “We are grateful that CMS came to the right decision after listening to stakeholders.”

An analysis of the proposed demonstration project by Avalere found that specialists would likely see a decrease in their drug payments under the proposal, while primary care doctors would likely see an increase, and that 7 of the 10 drugs most affected by this proposal were drugs used to treat cancer.

The AGA expressed concern that many of the drugs that gastroenterologists administer would be included in this proposed new payment model and that the model would affect the patients treated for the most complex conditions, such as Crohn’s disease and ulcerative colitis. Ultimately, this payment model would limit patient access to specialist care. The AGA urged CMS to include all stakeholders in the development of approaches to control Part B costs.

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A controversial demonstration project that would have tested new methods to pay for the drugs administered in medical offices has been canceled by the Centers for Medicare & Medicaid Services. The agency received considerable backlash from physicians, Congress, and others when the demonstration project was announced in March 2016.

anttohoho/Thinkstock
“After considering comments, CMS will not finalize the Medicare Part B Drug Payment Model during this administration,” the agency said in a statement. “The proposal was intended to test whether alternative drug payment structures would improve the quality of patient care and the value of Medicare drug spending.”

The agency said it received “a great deal of support from some” for the proposed demonstration. However, “a number of stakeholders expressed strong concerns about the model. While CMS was working to address these concerns, the complexity of the issues and the limited time available led to the decision not to finalize the rule at this time.”

The demonstration project was designed to test new methods to “improve how Medicare Part B pays for prescription drugs and supports physicians and other clinicians in delivering high quality care,” according to a fact sheet published in March.

Under the project, medical practices would have been divided into two groups. A control group would continue to be paid for Part B drugs at the current rate of 106% of average sales price (ASP), while the other would have been paid at 102.5% of ASP plus a flat fee of $16.80 per drug payment. Starting in January 2017, each group would have been further subdivided with a portion of each being subjected to value-based purchasing tools.

One key criticism of the demonstration project centered on the proposed randomization of practices, which was based on primary care service areas (clusters of zip codes with similar Part B medical care patterns). That randomization scheme could have caused different payment levels – and patient out-of-pocket spending – for geographically close areas. Further, participation in the demonstration project would have been mandatory, with no mechanism to opt out.

“This is a model for how Washington should, but often doesn’t, work,” American Medical Association President Andrew W. Gurman, MD, said in a statement. “We are grateful that CMS came to the right decision after listening to stakeholders.”

An analysis of the proposed demonstration project by Avalere found that specialists would likely see a decrease in their drug payments under the proposal, while primary care doctors would likely see an increase, and that 7 of the 10 drugs most affected by this proposal were drugs used to treat cancer.

The AGA expressed concern that many of the drugs that gastroenterologists administer would be included in this proposed new payment model and that the model would affect the patients treated for the most complex conditions, such as Crohn’s disease and ulcerative colitis. Ultimately, this payment model would limit patient access to specialist care. The AGA urged CMS to include all stakeholders in the development of approaches to control Part B costs.

 

A controversial demonstration project that would have tested new methods to pay for the drugs administered in medical offices has been canceled by the Centers for Medicare & Medicaid Services. The agency received considerable backlash from physicians, Congress, and others when the demonstration project was announced in March 2016.

anttohoho/Thinkstock
“After considering comments, CMS will not finalize the Medicare Part B Drug Payment Model during this administration,” the agency said in a statement. “The proposal was intended to test whether alternative drug payment structures would improve the quality of patient care and the value of Medicare drug spending.”

The agency said it received “a great deal of support from some” for the proposed demonstration. However, “a number of stakeholders expressed strong concerns about the model. While CMS was working to address these concerns, the complexity of the issues and the limited time available led to the decision not to finalize the rule at this time.”

The demonstration project was designed to test new methods to “improve how Medicare Part B pays for prescription drugs and supports physicians and other clinicians in delivering high quality care,” according to a fact sheet published in March.

Under the project, medical practices would have been divided into two groups. A control group would continue to be paid for Part B drugs at the current rate of 106% of average sales price (ASP), while the other would have been paid at 102.5% of ASP plus a flat fee of $16.80 per drug payment. Starting in January 2017, each group would have been further subdivided with a portion of each being subjected to value-based purchasing tools.

One key criticism of the demonstration project centered on the proposed randomization of practices, which was based on primary care service areas (clusters of zip codes with similar Part B medical care patterns). That randomization scheme could have caused different payment levels – and patient out-of-pocket spending – for geographically close areas. Further, participation in the demonstration project would have been mandatory, with no mechanism to opt out.

“This is a model for how Washington should, but often doesn’t, work,” American Medical Association President Andrew W. Gurman, MD, said in a statement. “We are grateful that CMS came to the right decision after listening to stakeholders.”

An analysis of the proposed demonstration project by Avalere found that specialists would likely see a decrease in their drug payments under the proposal, while primary care doctors would likely see an increase, and that 7 of the 10 drugs most affected by this proposal were drugs used to treat cancer.

The AGA expressed concern that many of the drugs that gastroenterologists administer would be included in this proposed new payment model and that the model would affect the patients treated for the most complex conditions, such as Crohn’s disease and ulcerative colitis. Ultimately, this payment model would limit patient access to specialist care. The AGA urged CMS to include all stakeholders in the development of approaches to control Part B costs.

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Continuous glucose monitoring benefits patients with type 1 diabetes

A few concerns with CGM
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A 6-month course of continuous glucose monitoring modestly cut hemoglobin A1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

Body

 

Both of these studies show a clear benefit with continuous glucose monitoring in patients with type 1 diabetes, but there are a few concerns.

First, CGM is expensive, and insurers may be reluctant to pay for this device in light of the relatively modest benefits reported by Beck et al. and Lind et al. Second, CGM is invasive and still requires patients to monitor their blood glucose with needle sticks several times per day – two factors that may limit its acceptability to many patients.

Third, the clinicians in these trials were experienced with using CGM and instructing patients in its use. Most clinicians who are not endocrinologists, and even some endocrinologists, would not have the time to manage the volume of data generated by the device and to guide patients’ lifestyle and insulin dosage changes accordingly, given the current time constraints in managing diabetes care.

Mayer B. Davidson, MD, is at Charles R. Drew University of Medicine and Science, Los Angeles. He reported having no relevant financial disclosures. Dr. Davidson made these remarks in an editorial accompanying the two reports (JAMA. 2017;317:363-4).

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Both of these studies show a clear benefit with continuous glucose monitoring in patients with type 1 diabetes, but there are a few concerns.

First, CGM is expensive, and insurers may be reluctant to pay for this device in light of the relatively modest benefits reported by Beck et al. and Lind et al. Second, CGM is invasive and still requires patients to monitor their blood glucose with needle sticks several times per day – two factors that may limit its acceptability to many patients.

Third, the clinicians in these trials were experienced with using CGM and instructing patients in its use. Most clinicians who are not endocrinologists, and even some endocrinologists, would not have the time to manage the volume of data generated by the device and to guide patients’ lifestyle and insulin dosage changes accordingly, given the current time constraints in managing diabetes care.

Mayer B. Davidson, MD, is at Charles R. Drew University of Medicine and Science, Los Angeles. He reported having no relevant financial disclosures. Dr. Davidson made these remarks in an editorial accompanying the two reports (JAMA. 2017;317:363-4).

Body

 

Both of these studies show a clear benefit with continuous glucose monitoring in patients with type 1 diabetes, but there are a few concerns.

First, CGM is expensive, and insurers may be reluctant to pay for this device in light of the relatively modest benefits reported by Beck et al. and Lind et al. Second, CGM is invasive and still requires patients to monitor their blood glucose with needle sticks several times per day – two factors that may limit its acceptability to many patients.

Third, the clinicians in these trials were experienced with using CGM and instructing patients in its use. Most clinicians who are not endocrinologists, and even some endocrinologists, would not have the time to manage the volume of data generated by the device and to guide patients’ lifestyle and insulin dosage changes accordingly, given the current time constraints in managing diabetes care.

Mayer B. Davidson, MD, is at Charles R. Drew University of Medicine and Science, Los Angeles. He reported having no relevant financial disclosures. Dr. Davidson made these remarks in an editorial accompanying the two reports (JAMA. 2017;317:363-4).

Title
A few concerns with CGM
A few concerns with CGM

 

A 6-month course of continuous glucose monitoring modestly cut hemoglobin A1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

 

A 6-month course of continuous glucose monitoring modestly cut hemoglobin A1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

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Key clinical point: A 6-month course of continuous glucose monitoring modestly reduced HbA1c levels in patients with type 1 diabetes who used multiple daily insulin injections.

Major finding: Compared with usual care, continuous glucose monitoring decreased mean HbA1c by 0.6% in a multicenter open-label U.S. study involving 158 participants and by 0.4% in a multicenter open-label crossover trial in Sweden.

Data source: Two separate short-term randomized trials comparing the effect of continuous glucose monitoring against usual care in 319 adults with type 1 diabetes.

Disclosures: Dr. Beck’s study was sponsored by Dexcom, maker of the CGM device, which also participated in designing the study, writing the protocol, reviewing and approving the manuscripts, and interpreting the data. Dr. Beck reported financial relationships with Dexcom and Abbott Diabetes Care, and his associates reported ties to numerous industry sources. Dr. Lind’s study was sponsored by the NU Hospital Group and Dexcom. Dr. Lind reported financial relationships with AstraZeneca, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Rubin Medical, and his associates reported ties to numerous industry sources.

USPSTF punts on sleep apnea screening

Don’t misinterpret the USPSTF recommendation
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The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

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This recommendation must not be misinterpreted. If clinicians are discouraged from directly questioning patients about apnea signs and symptoms or from using short screening questionnaires to identify those at high risk for the disorder, it would negatively influence public health.

Dr. Susan Redline
Primary care clinicians have an important role in mitigating the adverse health consequences of obstructive sleep apnea, which can stem from years of unrecognized disease.
 

Susan Redline, MD, is at the Sleep Health Institute and in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital and Harvard Medical School and Beth Israel Deaconess Medical Center, all in Boston. She reported ties to Jazz Pharmaceuticals, RosMed Inc., and the Beckman Company, as well as serving on the American Academy of Sleep Medicine’s board of directors. Dr. Redline made these remarks in an editorial accompanying the USPSTF reports (JAMA 2017;317:368-70).

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This recommendation must not be misinterpreted. If clinicians are discouraged from directly questioning patients about apnea signs and symptoms or from using short screening questionnaires to identify those at high risk for the disorder, it would negatively influence public health.

Dr. Susan Redline
Primary care clinicians have an important role in mitigating the adverse health consequences of obstructive sleep apnea, which can stem from years of unrecognized disease.
 

Susan Redline, MD, is at the Sleep Health Institute and in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital and Harvard Medical School and Beth Israel Deaconess Medical Center, all in Boston. She reported ties to Jazz Pharmaceuticals, RosMed Inc., and the Beckman Company, as well as serving on the American Academy of Sleep Medicine’s board of directors. Dr. Redline made these remarks in an editorial accompanying the USPSTF reports (JAMA 2017;317:368-70).

Body

 

This recommendation must not be misinterpreted. If clinicians are discouraged from directly questioning patients about apnea signs and symptoms or from using short screening questionnaires to identify those at high risk for the disorder, it would negatively influence public health.

Dr. Susan Redline
Primary care clinicians have an important role in mitigating the adverse health consequences of obstructive sleep apnea, which can stem from years of unrecognized disease.
 

Susan Redline, MD, is at the Sleep Health Institute and in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital and Harvard Medical School and Beth Israel Deaconess Medical Center, all in Boston. She reported ties to Jazz Pharmaceuticals, RosMed Inc., and the Beckman Company, as well as serving on the American Academy of Sleep Medicine’s board of directors. Dr. Redline made these remarks in an editorial accompanying the USPSTF reports (JAMA 2017;317:368-70).

Title
Don’t misinterpret the USPSTF recommendation
Don’t misinterpret the USPSTF recommendation

 

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

 

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

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FDA approves topical oxymetazoline for rosacea

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A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

In a press statement, Allergan cited results from two vehicle-controlled trials in which 885 adults with moderate to severe rosacea (79% female, 90% white) were randomized to treatment with oxymetazoline HCl or a vehicle cream for 29 days. At day 29, 12%-18% of patients in the active treatment arms had a 2-grade or better improvement from baseline (measured day 1, before the first dose) 3-12 hours after applying the medication, compared with 5%-9% for the vehicle cream arms. Outcomes were measured using combined patient and clinician erythema assessment scales.

Safety results from three pooled trials showed 2% of patients in the active treatment arms (489 people) had treatment-site dermatitis, and 1% had worsening of rosacea symptoms, pruritus, or pain. The vehicle cream groups (483 people) experienced similar rates of pruritus but negligible rates of other adverse effects, according to the prescribing information.

Brimonidine (Mirvaso) is another topical treatment approved by the FDA for treating rosacea, and its active ingredient is also an alpha-adrenergic agonist that works on the cutaneous microvasculature. However, there are differences in the two agents’ activity. Oxymetazoline acts on alpha1A receptors and brimonidine on alpha2 receptors. There have been reports of rebound erythema more severe than at baseline with brimonidine, and its manufacturer, Galderma, acknowledges the phenomenon in patient labeling.

When Allergan announced the FDA application for oxymetazoline in May 2016, it issued a press statement, describing oxymetazoline as a “sympathomimetic agonist that is selective for the alpha1A adrenoceptor or over other alpha1 adrenoceptors and nonselective for the alpha2 adrenoceptors.”In a 1-year open label trial of oxymetazoline (440 people), 3% of patients had worsening inflammatory lesions of rosacea, according to the prescribing information for oxymetazoline HCl 1%.
 

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A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

In a press statement, Allergan cited results from two vehicle-controlled trials in which 885 adults with moderate to severe rosacea (79% female, 90% white) were randomized to treatment with oxymetazoline HCl or a vehicle cream for 29 days. At day 29, 12%-18% of patients in the active treatment arms had a 2-grade or better improvement from baseline (measured day 1, before the first dose) 3-12 hours after applying the medication, compared with 5%-9% for the vehicle cream arms. Outcomes were measured using combined patient and clinician erythema assessment scales.

Safety results from three pooled trials showed 2% of patients in the active treatment arms (489 people) had treatment-site dermatitis, and 1% had worsening of rosacea symptoms, pruritus, or pain. The vehicle cream groups (483 people) experienced similar rates of pruritus but negligible rates of other adverse effects, according to the prescribing information.

Brimonidine (Mirvaso) is another topical treatment approved by the FDA for treating rosacea, and its active ingredient is also an alpha-adrenergic agonist that works on the cutaneous microvasculature. However, there are differences in the two agents’ activity. Oxymetazoline acts on alpha1A receptors and brimonidine on alpha2 receptors. There have been reports of rebound erythema more severe than at baseline with brimonidine, and its manufacturer, Galderma, acknowledges the phenomenon in patient labeling.

When Allergan announced the FDA application for oxymetazoline in May 2016, it issued a press statement, describing oxymetazoline as a “sympathomimetic agonist that is selective for the alpha1A adrenoceptor or over other alpha1 adrenoceptors and nonselective for the alpha2 adrenoceptors.”In a 1-year open label trial of oxymetazoline (440 people), 3% of patients had worsening inflammatory lesions of rosacea, according to the prescribing information for oxymetazoline HCl 1%.
 

 

A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

In a press statement, Allergan cited results from two vehicle-controlled trials in which 885 adults with moderate to severe rosacea (79% female, 90% white) were randomized to treatment with oxymetazoline HCl or a vehicle cream for 29 days. At day 29, 12%-18% of patients in the active treatment arms had a 2-grade or better improvement from baseline (measured day 1, before the first dose) 3-12 hours after applying the medication, compared with 5%-9% for the vehicle cream arms. Outcomes were measured using combined patient and clinician erythema assessment scales.

Safety results from three pooled trials showed 2% of patients in the active treatment arms (489 people) had treatment-site dermatitis, and 1% had worsening of rosacea symptoms, pruritus, or pain. The vehicle cream groups (483 people) experienced similar rates of pruritus but negligible rates of other adverse effects, according to the prescribing information.

Brimonidine (Mirvaso) is another topical treatment approved by the FDA for treating rosacea, and its active ingredient is also an alpha-adrenergic agonist that works on the cutaneous microvasculature. However, there are differences in the two agents’ activity. Oxymetazoline acts on alpha1A receptors and brimonidine on alpha2 receptors. There have been reports of rebound erythema more severe than at baseline with brimonidine, and its manufacturer, Galderma, acknowledges the phenomenon in patient labeling.

When Allergan announced the FDA application for oxymetazoline in May 2016, it issued a press statement, describing oxymetazoline as a “sympathomimetic agonist that is selective for the alpha1A adrenoceptor or over other alpha1 adrenoceptors and nonselective for the alpha2 adrenoceptors.”In a 1-year open label trial of oxymetazoline (440 people), 3% of patients had worsening inflammatory lesions of rosacea, according to the prescribing information for oxymetazoline HCl 1%.
 

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