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10 Important VA Studies You Might Have Missed at ASH
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
How often is AED treatment delayed for patients with epilepsy?
NEW ORLEANS – , according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.
“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.
Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.
The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.
In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.
Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.
Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.
Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.
“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.
More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.
This study was supported by a grant from UCB Pharma.
SOURCE: Chen Z et al. AES 2018, Abstract 3.421.
NEW ORLEANS – , according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.
“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.
Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.
The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.
In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.
Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.
Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.
Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.
“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.
More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.
This study was supported by a grant from UCB Pharma.
SOURCE: Chen Z et al. AES 2018, Abstract 3.421.
NEW ORLEANS – , according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.
“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.
Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.
The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.
In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.
Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.
Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.
Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.
“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.
More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.
This study was supported by a grant from UCB Pharma.
SOURCE: Chen Z et al. AES 2018, Abstract 3.421.
REPORTING FROM AES 2018
Key clinical point: Delayed initiation of antiepileptic drug treatment may be more common than thought.
Major finding: More than 30% of patients with epilepsy do not initiate treatment at diagnosis.
Study details: Review of 610 patients with newly diagnosed epilepsy who were seen at clinics in Western Australia.
Disclosures: The study was supported by a grant from UCB Pharma.
Source: Chen Z et al. AES 2018, Abstract 3.421.
Motor neuron disease spasticity improved with cannabis-based oral spray, antispasticity drugs
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
FROM THE LANCET NEUROLOGY
Key clinical point:
Major finding: In the nabiximols group, Modified Ashworth Scale scores improved by mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group.
Study details: A multicenter, double-blinded, randomized, placebo-controlled, phase 2 trial of 59 participants with spasticity symptoms from motor neuron disease from four tertiary motor neuron centers in Italy.
Disclosures: The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
Source: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X
Baricitinib study highlights power of placebo effect in RA
CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology.
That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.
He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.
Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.
In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.
At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.
Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.
Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.
Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.
During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.
Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.
The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.
SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.
CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology.
That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.
He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.
Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.
In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.
At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.
Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.
Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.
Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.
During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.
Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.
The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.
SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.
CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology.
That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.
He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.
Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.
In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.
At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.
Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.
Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.
Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.
During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.
Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.
The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.
SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Never underestimate the potency of the placebo effect in RA.
Major finding: After 100 weeks on oral baricitinib, 78.2% of RA patients had low disease activity and 31.6% were in remission.
Study details: This was an analysis of 619 rheumatoid arthritis patients who participated in RA-BEYOND, a phase 3, 48-week, long-term extension study built upon the earlier 52-week RA-BEAM trial.
Disclosures: Eli Lilly sponsored the study. The presenter serves as a paid consultant to that pharmaceutical company and more than a dozen others.
Source: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.
Extended AI therapy reduces breast cancer recurrence risk, ups fracture risk
SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.
The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.
The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.
However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.
In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.
The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.
Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.
Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.
The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.
Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”
In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.
Dr. Gray reported having no disclosures.
SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.
SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.
The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.
The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.
However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.
In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.
The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.
Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.
Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.
The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.
Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”
In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.
Dr. Gray reported having no disclosures.
SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.
SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.
The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.
The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.
However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.
In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.
The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.
Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.
Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.
The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.
Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”
In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.
Dr. Gray reported having no disclosures.
SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.
REPORTING FROM SABCS 2018
Key clinical point: Five extra years of aromatase inhibitor therapy reduces breast cancer recurrence, but increases fracture risk.
Major finding: Extending AI therapy by 5 years reduces breast cancer recurrence by 20% to 35%.
Study details: A meta-analysis of more than 22,000 women from 12 trials.
Disclosures: Dr. Gray reported having no disclosures.
Source: Gray R et al. SABCS 2018: Abstract GS3-03.
Class-action suit filed against ABIM over MOC
A group of internists is suing the American Board of Internal Medicine over its maintenance of certification (MOC) process, alleging that the board is monopolizing the MOC market.
The lawsuit, filed Dec. 6 in Pennsylvania district court, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. The plaintiffs seek damages and injunctive relief, plus lawsuit and attorney costs arising from ABIM’s alleged antitrust violations.
In a statement, ABIM expressed disappointment at the lawsuit and said the organization will vigorously defend itself, adding that doing so will “consume resources far better dedicated to continuous improvement of its programs.”
ABIM declined to answer questions addressing specific accusations from the lawsuit. However, in an interview, ABIM President Richard Baron, MD, said that “ABIM board-certified physicians have taken the initiative to distinguish themselves. This is a credential that physicians earn. We offer certified physicians the opportunity to demonstrate to the medical community, their peers, and the public that they are current and have special expertise.”
ABIM has not yet filed a formal response to the lawsuit, which was due by Jan. 6. Court documents show that in January, ABIM entered the appearances of four attorneys that will represent the board in the case. From there, discovery and evidence gathering in the case will begin.
Katherine Murray Leisure, MD, an infectious disease specialist based in Plymouth, Mass., is one of the plaintiffs. While she said that she could not comment specifically on the lawsuit, she has written publicly about her ABIM concerns in the past.
In a 2015 letter to Dr. Baron and posted on an anti-MOC website, Dr. Murray outlined a litany of complaints against ABIM’s MOC process and called on the U.S. Congress to investigate ABIM’s financial, legal, and ethical conduct.
“[The American Board of Medical Specialties] and ABIM collected more than $10,000 in fees and lost practice hours every decade from each [diplomate] doing MOC,” Dr. Murray Leisure wrote. “MOC took weeks away from our offices, clinics, patients, families, specialty societies, and individual research. ABMS MOC removed hundreds, perhaps thousands … of America’s best, once board-certified physicians from full hospital careers and earnings whenever [diplomates] did not complete these high-stakes MOC programs. … The righteous and fast solution to such moral, ethical, scientific, and constitutional problems is to end MOC now.”
Plaintiffs Glen Dela Cruz Manalo, MD; Alexa Joshua, MD; and Gerard Kenney, MD, did not return messages seeking comment. When contacted, attorneys for the plaintiffs declined to comment.
The doctors’ 32-page lawsuit characterizes ABIM as an organization motivated by money that has made its MOC process increasingly more burdensome for physicians over the years without evidence that MOC has any beneficial impact on doctors, patients, or the public. Complying with ABIM’s MOC costs internists an average of $23,607 in financial cost and time lost over 10 years, and costs up to $40,495 for some specialists, according to the suit.
The physicians allege that ABIM controls in excess of 95% of the market for MOC of internists, in violation of federal antitrust laws, and that the organization has unlawfully obtained and maintained monopoly power for MOC services.
The board’s illegal tying of its initial certification to its MOC results in burdensome conditions, including “raising the cost of the practice of medicine, constraining the supply of internists thereby harming competition, decreasing the supply of certified internists, and increasing the cost of medical services to patients and consumers,” the suit claims.
The legal challenge details how MOC has personally and professionally impacted each of the four plaintiffs. Dr. Manalo, a gastroenterologist, lost his privileges at St. Vincent Healthcare in Billings, Mont., and was subsequently terminated after he declined to maintain his ABIM certification as a gastroenterologist. In a letter to ABIM, Dr. Manalo wrote that it was “unfair and outright discriminatory that practitioners certified on or after 1990 are the only ones required to certify,” according to the lawsuit. Dr. Manalo later took a position as staff gastroenterologist at Jonathan M. Wainwright Memorial Veterans Affairs Medical Center in Walla Walla, Wash., at a substantially reduced salary. He became unemployed in 2017.
Dr. Murray Leisure obtained an initial and lifelong board certification in internal medicine from ABIM in 1984 and an infectious disease certification in 1990. ABlM terminated Dr. Murray’s infectious diseases certification after she failed her MOC examination in 2009, which led to lost privileges at Jordan Hospital in Plymouth, Mass. The loss caused significant damage to Dr. Murray, including lost income, a tarnished reputation, and the lost opportunity to help patients, according to the lawsuit. Jordan Hospital restored her privileges after Dr. Murray passed her MOC examination in 2012.
Dr. Kenney lost a job opportunity with Mount Nittany Physicians Group in State College, Pa., after he declined to renew his ABIM certification in gastroenterology. He is currently a physician with the University of Pittsburgh Medical Center in Seneca, Pa.
That the ABIM website lists him as “not certified,” is misleading, and makes it appear that his initial certifications were revoked due to failure to pass a MOC examination or misconduct, rather than because the certifications lapsed, according to the suit. The description makes Dr. Kenney appear less qualified to patients, hospitals, insurance companies, medical corporations, other employers, and others, he claims.
Dr. Joshua could not renew her consulting and admitting privileges at Detroit Medical Center after she failed an MOC examination in 2014 and became uncertified in internal medicine, according to the suit. In addition, Blue Cross Blue Shield informed Dr. Joshua it would no longer cover her because it required ABIM certification for coverage. She unsuccessfully appealed based on her certification with the National Board of Physicians and Surgeons. As a result of her certification termination, Dr. Joshua can only practice outpatient medicine at Detroit Medical Center.
In an interview, Dr. Baron emphasized the number of modifications made to its MOC process in recent years after responding to physician concerns. This includes an overhaul of the organization’s governance structure to include more than 200 practicing physicians and opening new avenues for physicians to engage in the creation of assessment content that more closely reflects what they see in practice, he said. In addition, ABIM now surveys all specialists to contribute to the exam blueprint review and the creation of the new Item Writing Task Force.
“We take all suggestions from physicians seriously, and have used it to launch many new initiatives including: the Knowledge Check-In, a new Physician Portal, partnerships to give physicians dual credit for CME and MOC, and exploration of alternative assessment models with medical societies,” he said.
Dr. Baron acknowledged past criticism of the MOC process, but said he is proud of the work ABIM has done to address physician concerns about the choice, relevance, and convenience of its MOC program.
*This story was updated on Feb. 6, 2019.
A group of internists is suing the American Board of Internal Medicine over its maintenance of certification (MOC) process, alleging that the board is monopolizing the MOC market.
The lawsuit, filed Dec. 6 in Pennsylvania district court, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. The plaintiffs seek damages and injunctive relief, plus lawsuit and attorney costs arising from ABIM’s alleged antitrust violations.
In a statement, ABIM expressed disappointment at the lawsuit and said the organization will vigorously defend itself, adding that doing so will “consume resources far better dedicated to continuous improvement of its programs.”
ABIM declined to answer questions addressing specific accusations from the lawsuit. However, in an interview, ABIM President Richard Baron, MD, said that “ABIM board-certified physicians have taken the initiative to distinguish themselves. This is a credential that physicians earn. We offer certified physicians the opportunity to demonstrate to the medical community, their peers, and the public that they are current and have special expertise.”
ABIM has not yet filed a formal response to the lawsuit, which was due by Jan. 6. Court documents show that in January, ABIM entered the appearances of four attorneys that will represent the board in the case. From there, discovery and evidence gathering in the case will begin.
Katherine Murray Leisure, MD, an infectious disease specialist based in Plymouth, Mass., is one of the plaintiffs. While she said that she could not comment specifically on the lawsuit, she has written publicly about her ABIM concerns in the past.
In a 2015 letter to Dr. Baron and posted on an anti-MOC website, Dr. Murray outlined a litany of complaints against ABIM’s MOC process and called on the U.S. Congress to investigate ABIM’s financial, legal, and ethical conduct.
“[The American Board of Medical Specialties] and ABIM collected more than $10,000 in fees and lost practice hours every decade from each [diplomate] doing MOC,” Dr. Murray Leisure wrote. “MOC took weeks away from our offices, clinics, patients, families, specialty societies, and individual research. ABMS MOC removed hundreds, perhaps thousands … of America’s best, once board-certified physicians from full hospital careers and earnings whenever [diplomates] did not complete these high-stakes MOC programs. … The righteous and fast solution to such moral, ethical, scientific, and constitutional problems is to end MOC now.”
Plaintiffs Glen Dela Cruz Manalo, MD; Alexa Joshua, MD; and Gerard Kenney, MD, did not return messages seeking comment. When contacted, attorneys for the plaintiffs declined to comment.
The doctors’ 32-page lawsuit characterizes ABIM as an organization motivated by money that has made its MOC process increasingly more burdensome for physicians over the years without evidence that MOC has any beneficial impact on doctors, patients, or the public. Complying with ABIM’s MOC costs internists an average of $23,607 in financial cost and time lost over 10 years, and costs up to $40,495 for some specialists, according to the suit.
The physicians allege that ABIM controls in excess of 95% of the market for MOC of internists, in violation of federal antitrust laws, and that the organization has unlawfully obtained and maintained monopoly power for MOC services.
The board’s illegal tying of its initial certification to its MOC results in burdensome conditions, including “raising the cost of the practice of medicine, constraining the supply of internists thereby harming competition, decreasing the supply of certified internists, and increasing the cost of medical services to patients and consumers,” the suit claims.
The legal challenge details how MOC has personally and professionally impacted each of the four plaintiffs. Dr. Manalo, a gastroenterologist, lost his privileges at St. Vincent Healthcare in Billings, Mont., and was subsequently terminated after he declined to maintain his ABIM certification as a gastroenterologist. In a letter to ABIM, Dr. Manalo wrote that it was “unfair and outright discriminatory that practitioners certified on or after 1990 are the only ones required to certify,” according to the lawsuit. Dr. Manalo later took a position as staff gastroenterologist at Jonathan M. Wainwright Memorial Veterans Affairs Medical Center in Walla Walla, Wash., at a substantially reduced salary. He became unemployed in 2017.
Dr. Murray Leisure obtained an initial and lifelong board certification in internal medicine from ABIM in 1984 and an infectious disease certification in 1990. ABlM terminated Dr. Murray’s infectious diseases certification after she failed her MOC examination in 2009, which led to lost privileges at Jordan Hospital in Plymouth, Mass. The loss caused significant damage to Dr. Murray, including lost income, a tarnished reputation, and the lost opportunity to help patients, according to the lawsuit. Jordan Hospital restored her privileges after Dr. Murray passed her MOC examination in 2012.
Dr. Kenney lost a job opportunity with Mount Nittany Physicians Group in State College, Pa., after he declined to renew his ABIM certification in gastroenterology. He is currently a physician with the University of Pittsburgh Medical Center in Seneca, Pa.
That the ABIM website lists him as “not certified,” is misleading, and makes it appear that his initial certifications were revoked due to failure to pass a MOC examination or misconduct, rather than because the certifications lapsed, according to the suit. The description makes Dr. Kenney appear less qualified to patients, hospitals, insurance companies, medical corporations, other employers, and others, he claims.
Dr. Joshua could not renew her consulting and admitting privileges at Detroit Medical Center after she failed an MOC examination in 2014 and became uncertified in internal medicine, according to the suit. In addition, Blue Cross Blue Shield informed Dr. Joshua it would no longer cover her because it required ABIM certification for coverage. She unsuccessfully appealed based on her certification with the National Board of Physicians and Surgeons. As a result of her certification termination, Dr. Joshua can only practice outpatient medicine at Detroit Medical Center.
In an interview, Dr. Baron emphasized the number of modifications made to its MOC process in recent years after responding to physician concerns. This includes an overhaul of the organization’s governance structure to include more than 200 practicing physicians and opening new avenues for physicians to engage in the creation of assessment content that more closely reflects what they see in practice, he said. In addition, ABIM now surveys all specialists to contribute to the exam blueprint review and the creation of the new Item Writing Task Force.
“We take all suggestions from physicians seriously, and have used it to launch many new initiatives including: the Knowledge Check-In, a new Physician Portal, partnerships to give physicians dual credit for CME and MOC, and exploration of alternative assessment models with medical societies,” he said.
Dr. Baron acknowledged past criticism of the MOC process, but said he is proud of the work ABIM has done to address physician concerns about the choice, relevance, and convenience of its MOC program.
*This story was updated on Feb. 6, 2019.
A group of internists is suing the American Board of Internal Medicine over its maintenance of certification (MOC) process, alleging that the board is monopolizing the MOC market.
The lawsuit, filed Dec. 6 in Pennsylvania district court, claims that ABIM is charging inflated monopoly prices for maintaining certification, that the organization is forcing physicians to purchase MOC, and that ABIM is inducing employers and others to require ABIM certification. The four plaintiff-physicians are asking a judge to find ABIM in violation of federal antitrust law and to bar the board from continuing its MOC process. The suit is filed as a class action on behalf of all internists and subspecialists required by ABIM to purchase MOC to maintain their ABIM certifications. The plaintiffs seek damages and injunctive relief, plus lawsuit and attorney costs arising from ABIM’s alleged antitrust violations.
In a statement, ABIM expressed disappointment at the lawsuit and said the organization will vigorously defend itself, adding that doing so will “consume resources far better dedicated to continuous improvement of its programs.”
ABIM declined to answer questions addressing specific accusations from the lawsuit. However, in an interview, ABIM President Richard Baron, MD, said that “ABIM board-certified physicians have taken the initiative to distinguish themselves. This is a credential that physicians earn. We offer certified physicians the opportunity to demonstrate to the medical community, their peers, and the public that they are current and have special expertise.”
ABIM has not yet filed a formal response to the lawsuit, which was due by Jan. 6. Court documents show that in January, ABIM entered the appearances of four attorneys that will represent the board in the case. From there, discovery and evidence gathering in the case will begin.
Katherine Murray Leisure, MD, an infectious disease specialist based in Plymouth, Mass., is one of the plaintiffs. While she said that she could not comment specifically on the lawsuit, she has written publicly about her ABIM concerns in the past.
In a 2015 letter to Dr. Baron and posted on an anti-MOC website, Dr. Murray outlined a litany of complaints against ABIM’s MOC process and called on the U.S. Congress to investigate ABIM’s financial, legal, and ethical conduct.
“[The American Board of Medical Specialties] and ABIM collected more than $10,000 in fees and lost practice hours every decade from each [diplomate] doing MOC,” Dr. Murray Leisure wrote. “MOC took weeks away from our offices, clinics, patients, families, specialty societies, and individual research. ABMS MOC removed hundreds, perhaps thousands … of America’s best, once board-certified physicians from full hospital careers and earnings whenever [diplomates] did not complete these high-stakes MOC programs. … The righteous and fast solution to such moral, ethical, scientific, and constitutional problems is to end MOC now.”
Plaintiffs Glen Dela Cruz Manalo, MD; Alexa Joshua, MD; and Gerard Kenney, MD, did not return messages seeking comment. When contacted, attorneys for the plaintiffs declined to comment.
The doctors’ 32-page lawsuit characterizes ABIM as an organization motivated by money that has made its MOC process increasingly more burdensome for physicians over the years without evidence that MOC has any beneficial impact on doctors, patients, or the public. Complying with ABIM’s MOC costs internists an average of $23,607 in financial cost and time lost over 10 years, and costs up to $40,495 for some specialists, according to the suit.
The physicians allege that ABIM controls in excess of 95% of the market for MOC of internists, in violation of federal antitrust laws, and that the organization has unlawfully obtained and maintained monopoly power for MOC services.
The board’s illegal tying of its initial certification to its MOC results in burdensome conditions, including “raising the cost of the practice of medicine, constraining the supply of internists thereby harming competition, decreasing the supply of certified internists, and increasing the cost of medical services to patients and consumers,” the suit claims.
The legal challenge details how MOC has personally and professionally impacted each of the four plaintiffs. Dr. Manalo, a gastroenterologist, lost his privileges at St. Vincent Healthcare in Billings, Mont., and was subsequently terminated after he declined to maintain his ABIM certification as a gastroenterologist. In a letter to ABIM, Dr. Manalo wrote that it was “unfair and outright discriminatory that practitioners certified on or after 1990 are the only ones required to certify,” according to the lawsuit. Dr. Manalo later took a position as staff gastroenterologist at Jonathan M. Wainwright Memorial Veterans Affairs Medical Center in Walla Walla, Wash., at a substantially reduced salary. He became unemployed in 2017.
Dr. Murray Leisure obtained an initial and lifelong board certification in internal medicine from ABIM in 1984 and an infectious disease certification in 1990. ABlM terminated Dr. Murray’s infectious diseases certification after she failed her MOC examination in 2009, which led to lost privileges at Jordan Hospital in Plymouth, Mass. The loss caused significant damage to Dr. Murray, including lost income, a tarnished reputation, and the lost opportunity to help patients, according to the lawsuit. Jordan Hospital restored her privileges after Dr. Murray passed her MOC examination in 2012.
Dr. Kenney lost a job opportunity with Mount Nittany Physicians Group in State College, Pa., after he declined to renew his ABIM certification in gastroenterology. He is currently a physician with the University of Pittsburgh Medical Center in Seneca, Pa.
That the ABIM website lists him as “not certified,” is misleading, and makes it appear that his initial certifications were revoked due to failure to pass a MOC examination or misconduct, rather than because the certifications lapsed, according to the suit. The description makes Dr. Kenney appear less qualified to patients, hospitals, insurance companies, medical corporations, other employers, and others, he claims.
Dr. Joshua could not renew her consulting and admitting privileges at Detroit Medical Center after she failed an MOC examination in 2014 and became uncertified in internal medicine, according to the suit. In addition, Blue Cross Blue Shield informed Dr. Joshua it would no longer cover her because it required ABIM certification for coverage. She unsuccessfully appealed based on her certification with the National Board of Physicians and Surgeons. As a result of her certification termination, Dr. Joshua can only practice outpatient medicine at Detroit Medical Center.
In an interview, Dr. Baron emphasized the number of modifications made to its MOC process in recent years after responding to physician concerns. This includes an overhaul of the organization’s governance structure to include more than 200 practicing physicians and opening new avenues for physicians to engage in the creation of assessment content that more closely reflects what they see in practice, he said. In addition, ABIM now surveys all specialists to contribute to the exam blueprint review and the creation of the new Item Writing Task Force.
“We take all suggestions from physicians seriously, and have used it to launch many new initiatives including: the Knowledge Check-In, a new Physician Portal, partnerships to give physicians dual credit for CME and MOC, and exploration of alternative assessment models with medical societies,” he said.
Dr. Baron acknowledged past criticism of the MOC process, but said he is proud of the work ABIM has done to address physician concerns about the choice, relevance, and convenience of its MOC program.
*This story was updated on Feb. 6, 2019.
Oxybutynin rapidly quells hot flashes
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
REPORTING FROM SABCS 2018
Time for single payer? ColdironCare
At a New Year’s Eve party a few years back, I noticed a man sitting nearby clutching his left upper arm. He was ashen and obviously uncomfortable. Acute coronary insufficiency, I thought, and I asked him if I could call the life squad for him. “Oh no,” he said, “I have these spells several times a day, the nitro will kick in after a minute, and this will ease off.” I listened as he explained he had a “widow maker,” a 90% plus left main occlusion, but “I am Canadian, and my government is going to pay for my bypass,” he said. “I just have to wait 6 more weeks.” The irony? He was the son of our host, and we were sitting in his mothers’ multimillion dollar home in the Florida Keys. He could be in a Miami hospital’s operating room in an hour or 2.
Wow. Click. Got it.
Fast forward to a lobbying discussion on Capitol Hill: A sympathetic U.S. senator tossed me this softball: ‘What do you think about Medicare reimbursement?” I expect he thought I was going to complain about how bad Medicare is, about its failure to keep current with inflation (currently about 30% behind), and the obtuse quality metrics it now requires. Instead, I found myself saying, “Medicare is my most reliable payer, paying on time – in 2 weeks for clean claims – and the private insurers have beaten me up badly. Medicare is one of my best payers.”
Wrong answer, but true statement.
There is much talk these days about , particularly considering all the barriers to care. (See my recent column, “Produce and Promises.”) Physicians and patients endure a mutual misery inflicted by private insurance companies.
What to do about health care in America?
First, let’s deal with the extraordinary costs of health care in the United States – 19% of our gross domestic product. About 3%-4 % of this figure is an accounting gimmick, since it includes nursing home care, which is considered “domiciliary” care rather than health care in Europe. In addition, drug costs are higher in the U.S., largely to cover the development of new drugs that cost less in the rest of the world. Wait lists are largely unheard of in the United States, and if you have such ready capacity, that means you incur the costs of idle capacity. Also, rarely is a new miracle drug flatly denied for coverage in the United States. If you persist, you will usually get your drug.
We are a commodity-driven society, and that is the real reason that health care costs so much in this country. Hence, we come to the real debate, the “R” word. How do we ration access to care? (See my 2017 column, “Why the Affordable Care Act will be Greatly Modified.”)
There are a plethora of proposals to fund single payer out there, none of which address rationing. And while single payer affords free universal coverage, it does not assure better care. As health economist Devon Herrick, Ph.D., wrote in his health care blog in 2016: “A single payer is not some magical entity that rains down savings from Heaven by being unconcerned about profit. Rather, an efficient single payer operates more like a predatory HMO with no competition. It is currently in vogue for hipsters to matter-of-factly announce the simple solution to health reform is single payer. Be careful what you wish for; you may end up with Medicaid for All.”
In fact, if you try to ferret out how physician income will be affected by universal health care, there would be an estimated pay cut of 11%-40%, depending on how the numbers are manipulated.
Some single-payer proposals use the term “exchange rates,” which for the uninformed means Medicaid rates. In addition, payment is usually given to the local hospital system, or “authority” to dole out. I have a very bad feeling that any small practitioner in an office-based practice would be severely shortchanged in such a system. In fact, if you cut pay for office-based physicians at all, you may begin to see them disappear.
Policy wonks argue for pay cuts for American physicians because European physicians “make less money.” Those numbers are all wrong. U.S. physicians are paid for their work, and for their practice expense. That is, how much it costs to provide the service in their office, which is around 40%-50% of published income. In Europe, almost all procedures are performed in the hospital setting, and the hospital absorbs the practice expense, which is ignored in this current health care reform debate. (See my 2015 column, “Doctor, Why DO you get paid so much?”)
The big selling point of single payer for physicians is that they might have less paperwork and get paid more for seeing Medicaid patients. Yet the paperwork will persist to avoid lawsuits, electronic medical records are now ingrained into the system, and most Medicaid patients are currently seen in the federal or hospital outpatient clinic where higher rates or other subsidies are available. The comically low Medicaid rates paid to physician offices are largely evaded or not even filed for.
Single-payer advocates are basically saying, “Yes, you will be seeing patients at a loss but you will make it up in volume.” This ignores the reality that most physicians don’t need or want more volume.
Here is my plan for single-payer health care. Call it ColdironCare.
- Set payment rates for physicians at 130% of current Medicare, about where we were 30 years ago, considering inflation. Tie the reimbursement rate to the cost of living index, same as social security. If you cut physician pay 11%-40%, you will see mass retirement and the elimination of the most efficient care, office-based practice.
- Remove the practice expense payment from government-reported physician income since this is overhead spent to provide the care.
- Let all physicians participate, and don’t pay site-of-service differentials.
- Enact national tort reform, which would decrease the paperwork, overhead, and much useless defensive medicine.
- Press the generic drug manufacturers (but not the innovators) regarding drug costs. Bite the bullet, and set national coverage standards (ration care) to be revisited every 5 years, which will eliminate step therapy and prior authorizations. Allow individuals to pay out of pocket for additional treatments they want, including that questionable additional 90 days of life they may get from the $250,000 drug for the off-label indication.
- Press the hospitals, and don’t complain when many of them close, especially rural ones.
- Allow individuals, hospitals, and physicians to contract outside of the government plan (in contrast to Canada).
- Downsize the health insurance companies, and have them sell private supplemental insurance to whomever wants it.
Finally, make all of this a constitutional amendment. If not put out of reach, in 15 years we will have the same system we have today. The politicians simply will not be able to resist degrading (reforming, improving, refunding, defunding) the original plan. Or, you could simply increase Medicaid rates to Medicare rates and call it a day.
Oh, by the way, I saw that man from the New Year’s Eve party at the airport the following Christmas. He survived to get his government bypass and is doing well.
The health care system we have is miserable, except compared with all the others.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
At a New Year’s Eve party a few years back, I noticed a man sitting nearby clutching his left upper arm. He was ashen and obviously uncomfortable. Acute coronary insufficiency, I thought, and I asked him if I could call the life squad for him. “Oh no,” he said, “I have these spells several times a day, the nitro will kick in after a minute, and this will ease off.” I listened as he explained he had a “widow maker,” a 90% plus left main occlusion, but “I am Canadian, and my government is going to pay for my bypass,” he said. “I just have to wait 6 more weeks.” The irony? He was the son of our host, and we were sitting in his mothers’ multimillion dollar home in the Florida Keys. He could be in a Miami hospital’s operating room in an hour or 2.
Wow. Click. Got it.
Fast forward to a lobbying discussion on Capitol Hill: A sympathetic U.S. senator tossed me this softball: ‘What do you think about Medicare reimbursement?” I expect he thought I was going to complain about how bad Medicare is, about its failure to keep current with inflation (currently about 30% behind), and the obtuse quality metrics it now requires. Instead, I found myself saying, “Medicare is my most reliable payer, paying on time – in 2 weeks for clean claims – and the private insurers have beaten me up badly. Medicare is one of my best payers.”
Wrong answer, but true statement.
There is much talk these days about , particularly considering all the barriers to care. (See my recent column, “Produce and Promises.”) Physicians and patients endure a mutual misery inflicted by private insurance companies.
What to do about health care in America?
First, let’s deal with the extraordinary costs of health care in the United States – 19% of our gross domestic product. About 3%-4 % of this figure is an accounting gimmick, since it includes nursing home care, which is considered “domiciliary” care rather than health care in Europe. In addition, drug costs are higher in the U.S., largely to cover the development of new drugs that cost less in the rest of the world. Wait lists are largely unheard of in the United States, and if you have such ready capacity, that means you incur the costs of idle capacity. Also, rarely is a new miracle drug flatly denied for coverage in the United States. If you persist, you will usually get your drug.
We are a commodity-driven society, and that is the real reason that health care costs so much in this country. Hence, we come to the real debate, the “R” word. How do we ration access to care? (See my 2017 column, “Why the Affordable Care Act will be Greatly Modified.”)
There are a plethora of proposals to fund single payer out there, none of which address rationing. And while single payer affords free universal coverage, it does not assure better care. As health economist Devon Herrick, Ph.D., wrote in his health care blog in 2016: “A single payer is not some magical entity that rains down savings from Heaven by being unconcerned about profit. Rather, an efficient single payer operates more like a predatory HMO with no competition. It is currently in vogue for hipsters to matter-of-factly announce the simple solution to health reform is single payer. Be careful what you wish for; you may end up with Medicaid for All.”
In fact, if you try to ferret out how physician income will be affected by universal health care, there would be an estimated pay cut of 11%-40%, depending on how the numbers are manipulated.
Some single-payer proposals use the term “exchange rates,” which for the uninformed means Medicaid rates. In addition, payment is usually given to the local hospital system, or “authority” to dole out. I have a very bad feeling that any small practitioner in an office-based practice would be severely shortchanged in such a system. In fact, if you cut pay for office-based physicians at all, you may begin to see them disappear.
Policy wonks argue for pay cuts for American physicians because European physicians “make less money.” Those numbers are all wrong. U.S. physicians are paid for their work, and for their practice expense. That is, how much it costs to provide the service in their office, which is around 40%-50% of published income. In Europe, almost all procedures are performed in the hospital setting, and the hospital absorbs the practice expense, which is ignored in this current health care reform debate. (See my 2015 column, “Doctor, Why DO you get paid so much?”)
The big selling point of single payer for physicians is that they might have less paperwork and get paid more for seeing Medicaid patients. Yet the paperwork will persist to avoid lawsuits, electronic medical records are now ingrained into the system, and most Medicaid patients are currently seen in the federal or hospital outpatient clinic where higher rates or other subsidies are available. The comically low Medicaid rates paid to physician offices are largely evaded or not even filed for.
Single-payer advocates are basically saying, “Yes, you will be seeing patients at a loss but you will make it up in volume.” This ignores the reality that most physicians don’t need or want more volume.
Here is my plan for single-payer health care. Call it ColdironCare.
- Set payment rates for physicians at 130% of current Medicare, about where we were 30 years ago, considering inflation. Tie the reimbursement rate to the cost of living index, same as social security. If you cut physician pay 11%-40%, you will see mass retirement and the elimination of the most efficient care, office-based practice.
- Remove the practice expense payment from government-reported physician income since this is overhead spent to provide the care.
- Let all physicians participate, and don’t pay site-of-service differentials.
- Enact national tort reform, which would decrease the paperwork, overhead, and much useless defensive medicine.
- Press the generic drug manufacturers (but not the innovators) regarding drug costs. Bite the bullet, and set national coverage standards (ration care) to be revisited every 5 years, which will eliminate step therapy and prior authorizations. Allow individuals to pay out of pocket for additional treatments they want, including that questionable additional 90 days of life they may get from the $250,000 drug for the off-label indication.
- Press the hospitals, and don’t complain when many of them close, especially rural ones.
- Allow individuals, hospitals, and physicians to contract outside of the government plan (in contrast to Canada).
- Downsize the health insurance companies, and have them sell private supplemental insurance to whomever wants it.
Finally, make all of this a constitutional amendment. If not put out of reach, in 15 years we will have the same system we have today. The politicians simply will not be able to resist degrading (reforming, improving, refunding, defunding) the original plan. Or, you could simply increase Medicaid rates to Medicare rates and call it a day.
Oh, by the way, I saw that man from the New Year’s Eve party at the airport the following Christmas. He survived to get his government bypass and is doing well.
The health care system we have is miserable, except compared with all the others.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
At a New Year’s Eve party a few years back, I noticed a man sitting nearby clutching his left upper arm. He was ashen and obviously uncomfortable. Acute coronary insufficiency, I thought, and I asked him if I could call the life squad for him. “Oh no,” he said, “I have these spells several times a day, the nitro will kick in after a minute, and this will ease off.” I listened as he explained he had a “widow maker,” a 90% plus left main occlusion, but “I am Canadian, and my government is going to pay for my bypass,” he said. “I just have to wait 6 more weeks.” The irony? He was the son of our host, and we were sitting in his mothers’ multimillion dollar home in the Florida Keys. He could be in a Miami hospital’s operating room in an hour or 2.
Wow. Click. Got it.
Fast forward to a lobbying discussion on Capitol Hill: A sympathetic U.S. senator tossed me this softball: ‘What do you think about Medicare reimbursement?” I expect he thought I was going to complain about how bad Medicare is, about its failure to keep current with inflation (currently about 30% behind), and the obtuse quality metrics it now requires. Instead, I found myself saying, “Medicare is my most reliable payer, paying on time – in 2 weeks for clean claims – and the private insurers have beaten me up badly. Medicare is one of my best payers.”
Wrong answer, but true statement.
There is much talk these days about , particularly considering all the barriers to care. (See my recent column, “Produce and Promises.”) Physicians and patients endure a mutual misery inflicted by private insurance companies.
What to do about health care in America?
First, let’s deal with the extraordinary costs of health care in the United States – 19% of our gross domestic product. About 3%-4 % of this figure is an accounting gimmick, since it includes nursing home care, which is considered “domiciliary” care rather than health care in Europe. In addition, drug costs are higher in the U.S., largely to cover the development of new drugs that cost less in the rest of the world. Wait lists are largely unheard of in the United States, and if you have such ready capacity, that means you incur the costs of idle capacity. Also, rarely is a new miracle drug flatly denied for coverage in the United States. If you persist, you will usually get your drug.
We are a commodity-driven society, and that is the real reason that health care costs so much in this country. Hence, we come to the real debate, the “R” word. How do we ration access to care? (See my 2017 column, “Why the Affordable Care Act will be Greatly Modified.”)
There are a plethora of proposals to fund single payer out there, none of which address rationing. And while single payer affords free universal coverage, it does not assure better care. As health economist Devon Herrick, Ph.D., wrote in his health care blog in 2016: “A single payer is not some magical entity that rains down savings from Heaven by being unconcerned about profit. Rather, an efficient single payer operates more like a predatory HMO with no competition. It is currently in vogue for hipsters to matter-of-factly announce the simple solution to health reform is single payer. Be careful what you wish for; you may end up with Medicaid for All.”
In fact, if you try to ferret out how physician income will be affected by universal health care, there would be an estimated pay cut of 11%-40%, depending on how the numbers are manipulated.
Some single-payer proposals use the term “exchange rates,” which for the uninformed means Medicaid rates. In addition, payment is usually given to the local hospital system, or “authority” to dole out. I have a very bad feeling that any small practitioner in an office-based practice would be severely shortchanged in such a system. In fact, if you cut pay for office-based physicians at all, you may begin to see them disappear.
Policy wonks argue for pay cuts for American physicians because European physicians “make less money.” Those numbers are all wrong. U.S. physicians are paid for their work, and for their practice expense. That is, how much it costs to provide the service in their office, which is around 40%-50% of published income. In Europe, almost all procedures are performed in the hospital setting, and the hospital absorbs the practice expense, which is ignored in this current health care reform debate. (See my 2015 column, “Doctor, Why DO you get paid so much?”)
The big selling point of single payer for physicians is that they might have less paperwork and get paid more for seeing Medicaid patients. Yet the paperwork will persist to avoid lawsuits, electronic medical records are now ingrained into the system, and most Medicaid patients are currently seen in the federal or hospital outpatient clinic where higher rates or other subsidies are available. The comically low Medicaid rates paid to physician offices are largely evaded or not even filed for.
Single-payer advocates are basically saying, “Yes, you will be seeing patients at a loss but you will make it up in volume.” This ignores the reality that most physicians don’t need or want more volume.
Here is my plan for single-payer health care. Call it ColdironCare.
- Set payment rates for physicians at 130% of current Medicare, about where we were 30 years ago, considering inflation. Tie the reimbursement rate to the cost of living index, same as social security. If you cut physician pay 11%-40%, you will see mass retirement and the elimination of the most efficient care, office-based practice.
- Remove the practice expense payment from government-reported physician income since this is overhead spent to provide the care.
- Let all physicians participate, and don’t pay site-of-service differentials.
- Enact national tort reform, which would decrease the paperwork, overhead, and much useless defensive medicine.
- Press the generic drug manufacturers (but not the innovators) regarding drug costs. Bite the bullet, and set national coverage standards (ration care) to be revisited every 5 years, which will eliminate step therapy and prior authorizations. Allow individuals to pay out of pocket for additional treatments they want, including that questionable additional 90 days of life they may get from the $250,000 drug for the off-label indication.
- Press the hospitals, and don’t complain when many of them close, especially rural ones.
- Allow individuals, hospitals, and physicians to contract outside of the government plan (in contrast to Canada).
- Downsize the health insurance companies, and have them sell private supplemental insurance to whomever wants it.
Finally, make all of this a constitutional amendment. If not put out of reach, in 15 years we will have the same system we have today. The politicians simply will not be able to resist degrading (reforming, improving, refunding, defunding) the original plan. Or, you could simply increase Medicaid rates to Medicare rates and call it a day.
Oh, by the way, I saw that man from the New Year’s Eve party at the airport the following Christmas. He survived to get his government bypass and is doing well.
The health care system we have is miserable, except compared with all the others.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
Technical issues inhibit data collection on fentanyl
BONITA SPRINGS, FLA. – Systemic gaps inhibit the collection of data that could be helpful in combating skyrocketing fentanyl use in the United States, experts said at the annual meeting of the American Academy of Addiction Psychiatry.
Jane C. Maxwell, PhD, research professor at the Addiction Research Institute at the University of Texas at Austin, pointed to the Treatment Episode Data Set as an example. It includes client-level information on substance-use treatment admissions from state agencies, and it could be a good source of fentanyl data. The problem? The admissions data do not have a category for fentanyl.
“So we don’t even know who the users are in that data set,” Dr. Maxwell said.
When it comes to mortality, the data on fentanyl are sometimes available, but they are cumbersome to collect, she said. “The only way to get at fentanyl in the mortality data – because you’re going to get it under ‘synthetic opiates’ – is to get the literal texts that are written on the death certificates.” That requires hand-counting the cases of fentanyl in order to know whether a death was attributable to fentanyl or some other drug.
The data that are available paint a grim picture, with drug-poisoning deaths from “other synthetics,” the category that includes fentanyl, soaring since 2013, surging past deaths from heroin as the top killer, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The number of drug cases involving fentanyl jumped to 60,670 in 2017, up from 11,992 in 2015, according to a report from the National Forensic Laboratory Information System.
Dr. Maxwell said when she first heard the word “enigma” used to describe the fentanyl phenomenon, she thought it was a curious word choice. But as she stepped back and looked at how deadly fentanyl is, and the gaps in what is really known about it, she reconsidered. she said.
In addition, Sandra D. Comer, PhD, noted that in 2006 a spike in fentanyl cases was described as an “epidemic,” before falling again. By 2015, the number of cases involving fentanyl was 8 times that “epidemic” amount, driven not by pharmaceutical product but by synthetic versions of the drug.
“There are hundreds of labs now that are making fentanyl,” said Dr. Comer, professor of neurobiology in the department of psychiatry at Columbia University in New York. “This is why the [Drug Enforcement Administration] has stated that they think it’s a problem that’s not going to go away any time soon.”
Dr. Maxwell reported no relevant disclosures. Dr. Comer reported consulting and collaboration with several companies, including Alkermes, Janssen, Mallinckrodt, and Sun Pharmaceutical.
BONITA SPRINGS, FLA. – Systemic gaps inhibit the collection of data that could be helpful in combating skyrocketing fentanyl use in the United States, experts said at the annual meeting of the American Academy of Addiction Psychiatry.
Jane C. Maxwell, PhD, research professor at the Addiction Research Institute at the University of Texas at Austin, pointed to the Treatment Episode Data Set as an example. It includes client-level information on substance-use treatment admissions from state agencies, and it could be a good source of fentanyl data. The problem? The admissions data do not have a category for fentanyl.
“So we don’t even know who the users are in that data set,” Dr. Maxwell said.
When it comes to mortality, the data on fentanyl are sometimes available, but they are cumbersome to collect, she said. “The only way to get at fentanyl in the mortality data – because you’re going to get it under ‘synthetic opiates’ – is to get the literal texts that are written on the death certificates.” That requires hand-counting the cases of fentanyl in order to know whether a death was attributable to fentanyl or some other drug.
The data that are available paint a grim picture, with drug-poisoning deaths from “other synthetics,” the category that includes fentanyl, soaring since 2013, surging past deaths from heroin as the top killer, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The number of drug cases involving fentanyl jumped to 60,670 in 2017, up from 11,992 in 2015, according to a report from the National Forensic Laboratory Information System.
Dr. Maxwell said when she first heard the word “enigma” used to describe the fentanyl phenomenon, she thought it was a curious word choice. But as she stepped back and looked at how deadly fentanyl is, and the gaps in what is really known about it, she reconsidered. she said.
In addition, Sandra D. Comer, PhD, noted that in 2006 a spike in fentanyl cases was described as an “epidemic,” before falling again. By 2015, the number of cases involving fentanyl was 8 times that “epidemic” amount, driven not by pharmaceutical product but by synthetic versions of the drug.
“There are hundreds of labs now that are making fentanyl,” said Dr. Comer, professor of neurobiology in the department of psychiatry at Columbia University in New York. “This is why the [Drug Enforcement Administration] has stated that they think it’s a problem that’s not going to go away any time soon.”
Dr. Maxwell reported no relevant disclosures. Dr. Comer reported consulting and collaboration with several companies, including Alkermes, Janssen, Mallinckrodt, and Sun Pharmaceutical.
BONITA SPRINGS, FLA. – Systemic gaps inhibit the collection of data that could be helpful in combating skyrocketing fentanyl use in the United States, experts said at the annual meeting of the American Academy of Addiction Psychiatry.
Jane C. Maxwell, PhD, research professor at the Addiction Research Institute at the University of Texas at Austin, pointed to the Treatment Episode Data Set as an example. It includes client-level information on substance-use treatment admissions from state agencies, and it could be a good source of fentanyl data. The problem? The admissions data do not have a category for fentanyl.
“So we don’t even know who the users are in that data set,” Dr. Maxwell said.
When it comes to mortality, the data on fentanyl are sometimes available, but they are cumbersome to collect, she said. “The only way to get at fentanyl in the mortality data – because you’re going to get it under ‘synthetic opiates’ – is to get the literal texts that are written on the death certificates.” That requires hand-counting the cases of fentanyl in order to know whether a death was attributable to fentanyl or some other drug.
The data that are available paint a grim picture, with drug-poisoning deaths from “other synthetics,” the category that includes fentanyl, soaring since 2013, surging past deaths from heroin as the top killer, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The number of drug cases involving fentanyl jumped to 60,670 in 2017, up from 11,992 in 2015, according to a report from the National Forensic Laboratory Information System.
Dr. Maxwell said when she first heard the word “enigma” used to describe the fentanyl phenomenon, she thought it was a curious word choice. But as she stepped back and looked at how deadly fentanyl is, and the gaps in what is really known about it, she reconsidered. she said.
In addition, Sandra D. Comer, PhD, noted that in 2006 a spike in fentanyl cases was described as an “epidemic,” before falling again. By 2015, the number of cases involving fentanyl was 8 times that “epidemic” amount, driven not by pharmaceutical product but by synthetic versions of the drug.
“There are hundreds of labs now that are making fentanyl,” said Dr. Comer, professor of neurobiology in the department of psychiatry at Columbia University in New York. “This is why the [Drug Enforcement Administration] has stated that they think it’s a problem that’s not going to go away any time soon.”
Dr. Maxwell reported no relevant disclosures. Dr. Comer reported consulting and collaboration with several companies, including Alkermes, Janssen, Mallinckrodt, and Sun Pharmaceutical.
REPORTING FROM AAAP 2018
Understanding properties of fentanyl, other opioids key to treatment
Naloxone increasingly coming up short, expert says
BONITA SPRINGS, FLA. – Treating disorders tied to the use of highly potent synthetic opioids (HPSO), such as fentanyl, is challenging at best, an expert said at the annual meeting of the American Academy of Addiction Psychiatry.
“We have essentially no data to guide pharmacotherapy management decisions for the leading cause of fatal overdose deaths in the U.S.,” said John J. Mariani, MD, associate professor of clinical psychiatry at Columbia University, New York. “In the absence of data to make evidence-based recommendations, we still need to treat patients.”
That means taking what is known about the properties of those drugs into account when making treatment decisions, he said. Fentanyl quickly crosses the blood-brain barrier and is rapidly distributed to peripheral tissue. It has a short duration of action, but its duration can be extended with multiple injections or an infusion, he said. Research suggests that it has opioid receptor affinity similar to that of morphine, and it’s not known why it is up to 100 times more potent than morphine.
From his own experience, he offered some suggestions on treating patients who use HPSOs:
- Buprenorphine: Clinicians using buprenorphine as induction treatment have to wait longer from the last use to the first dose because of its longer effective half-life, and other medications might be needed to manage withdrawal. For maintenance, higher doses possibly should be considered to prevent HPSO override and to maintain opioid tolerance.
- Extended-release naltrexone: This involves a more difficult induction, and there is a question of whether inpatient treatment is better than outpatient, he said. For maintenance, more frequent administration should be considered, with closer monitoring for the risk of override and more urine toxicology testing.
- Methadone: For induction, methadone could offer an advantage over buprenorphine, because there is no risk of precipitated withdrawal. For maintenance, Dr. Mariani said, it’s not known whether standard doses protect against raising tolerance out of the reach of HPSOs’ effects.
- Naloxone: He said there have been increasing reports of multiple doses being needed to reverse an overdose. Because of the shorter time between substance use and death with fentanyl, more reports have been filed on unsuccessful attempts to revive people with naloxone despite multiple doses or stronger doses. Some naloxone programs have been giving more than two standard doses or using devices that give higher doses, he said. Also, , he said.
Addiction psychiatrists “need to educate patients, families, and other clinicians of this new risk of using opioids,” he said.
Meanwhile, in another talk, Thomas Kosten, MD, described progress in the efforts to develop a vaccine against fentanyl addiction, in the hopes of preventing overdoses. Researchers are taking cues from the failed attempt to develop a cocaine vaccine a few years ago, in which not enough antibodies were produced in about half the patients.
This time, researchers are using toll-like receptor agonists to boost the effects of the main vaccine component, known as norcocaine. Those agonists can more than double the antibody increase that is seen without them, said Dr. Kosten, professor of psychiatry at Baylor College of Medicine, Houston.
So far, researchers have found that the vaccine produces blockade of fentanyl analgesia and respiratory depression in rats. Dr. Kosten said his lab is looking for funding to continue the research. “It looks like we’re going to have some money in February to start making the vaccine,” he said.
Dr. Mariani and Dr. Kosten reported no relevant disclosures.
Naloxone increasingly coming up short, expert says
Naloxone increasingly coming up short, expert says
BONITA SPRINGS, FLA. – Treating disorders tied to the use of highly potent synthetic opioids (HPSO), such as fentanyl, is challenging at best, an expert said at the annual meeting of the American Academy of Addiction Psychiatry.
“We have essentially no data to guide pharmacotherapy management decisions for the leading cause of fatal overdose deaths in the U.S.,” said John J. Mariani, MD, associate professor of clinical psychiatry at Columbia University, New York. “In the absence of data to make evidence-based recommendations, we still need to treat patients.”
That means taking what is known about the properties of those drugs into account when making treatment decisions, he said. Fentanyl quickly crosses the blood-brain barrier and is rapidly distributed to peripheral tissue. It has a short duration of action, but its duration can be extended with multiple injections or an infusion, he said. Research suggests that it has opioid receptor affinity similar to that of morphine, and it’s not known why it is up to 100 times more potent than morphine.
From his own experience, he offered some suggestions on treating patients who use HPSOs:
- Buprenorphine: Clinicians using buprenorphine as induction treatment have to wait longer from the last use to the first dose because of its longer effective half-life, and other medications might be needed to manage withdrawal. For maintenance, higher doses possibly should be considered to prevent HPSO override and to maintain opioid tolerance.
- Extended-release naltrexone: This involves a more difficult induction, and there is a question of whether inpatient treatment is better than outpatient, he said. For maintenance, more frequent administration should be considered, with closer monitoring for the risk of override and more urine toxicology testing.
- Methadone: For induction, methadone could offer an advantage over buprenorphine, because there is no risk of precipitated withdrawal. For maintenance, Dr. Mariani said, it’s not known whether standard doses protect against raising tolerance out of the reach of HPSOs’ effects.
- Naloxone: He said there have been increasing reports of multiple doses being needed to reverse an overdose. Because of the shorter time between substance use and death with fentanyl, more reports have been filed on unsuccessful attempts to revive people with naloxone despite multiple doses or stronger doses. Some naloxone programs have been giving more than two standard doses or using devices that give higher doses, he said. Also, , he said.
Addiction psychiatrists “need to educate patients, families, and other clinicians of this new risk of using opioids,” he said.
Meanwhile, in another talk, Thomas Kosten, MD, described progress in the efforts to develop a vaccine against fentanyl addiction, in the hopes of preventing overdoses. Researchers are taking cues from the failed attempt to develop a cocaine vaccine a few years ago, in which not enough antibodies were produced in about half the patients.
This time, researchers are using toll-like receptor agonists to boost the effects of the main vaccine component, known as norcocaine. Those agonists can more than double the antibody increase that is seen without them, said Dr. Kosten, professor of psychiatry at Baylor College of Medicine, Houston.
So far, researchers have found that the vaccine produces blockade of fentanyl analgesia and respiratory depression in rats. Dr. Kosten said his lab is looking for funding to continue the research. “It looks like we’re going to have some money in February to start making the vaccine,” he said.
Dr. Mariani and Dr. Kosten reported no relevant disclosures.
BONITA SPRINGS, FLA. – Treating disorders tied to the use of highly potent synthetic opioids (HPSO), such as fentanyl, is challenging at best, an expert said at the annual meeting of the American Academy of Addiction Psychiatry.
“We have essentially no data to guide pharmacotherapy management decisions for the leading cause of fatal overdose deaths in the U.S.,” said John J. Mariani, MD, associate professor of clinical psychiatry at Columbia University, New York. “In the absence of data to make evidence-based recommendations, we still need to treat patients.”
That means taking what is known about the properties of those drugs into account when making treatment decisions, he said. Fentanyl quickly crosses the blood-brain barrier and is rapidly distributed to peripheral tissue. It has a short duration of action, but its duration can be extended with multiple injections or an infusion, he said. Research suggests that it has opioid receptor affinity similar to that of morphine, and it’s not known why it is up to 100 times more potent than morphine.
From his own experience, he offered some suggestions on treating patients who use HPSOs:
- Buprenorphine: Clinicians using buprenorphine as induction treatment have to wait longer from the last use to the first dose because of its longer effective half-life, and other medications might be needed to manage withdrawal. For maintenance, higher doses possibly should be considered to prevent HPSO override and to maintain opioid tolerance.
- Extended-release naltrexone: This involves a more difficult induction, and there is a question of whether inpatient treatment is better than outpatient, he said. For maintenance, more frequent administration should be considered, with closer monitoring for the risk of override and more urine toxicology testing.
- Methadone: For induction, methadone could offer an advantage over buprenorphine, because there is no risk of precipitated withdrawal. For maintenance, Dr. Mariani said, it’s not known whether standard doses protect against raising tolerance out of the reach of HPSOs’ effects.
- Naloxone: He said there have been increasing reports of multiple doses being needed to reverse an overdose. Because of the shorter time between substance use and death with fentanyl, more reports have been filed on unsuccessful attempts to revive people with naloxone despite multiple doses or stronger doses. Some naloxone programs have been giving more than two standard doses or using devices that give higher doses, he said. Also, , he said.
Addiction psychiatrists “need to educate patients, families, and other clinicians of this new risk of using opioids,” he said.
Meanwhile, in another talk, Thomas Kosten, MD, described progress in the efforts to develop a vaccine against fentanyl addiction, in the hopes of preventing overdoses. Researchers are taking cues from the failed attempt to develop a cocaine vaccine a few years ago, in which not enough antibodies were produced in about half the patients.
This time, researchers are using toll-like receptor agonists to boost the effects of the main vaccine component, known as norcocaine. Those agonists can more than double the antibody increase that is seen without them, said Dr. Kosten, professor of psychiatry at Baylor College of Medicine, Houston.
So far, researchers have found that the vaccine produces blockade of fentanyl analgesia and respiratory depression in rats. Dr. Kosten said his lab is looking for funding to continue the research. “It looks like we’re going to have some money in February to start making the vaccine,” he said.
Dr. Mariani and Dr. Kosten reported no relevant disclosures.
REPORTING FROM AAAP 2018