Drug Therapy

SEATTLE – Neurologists who subspecialize in multiple sclerosis (MS) are more likely than are general neurologists to prescribe three out of five high-efficacy medications for patients with the condition, according to the findings from a single-system study. It is not clear if the greater reluctance among general neurologists to prescribe the drugs is hurting the health of patients, and the study does not examine whether general neurologists are referring their toughest patients to their subspecialist colleagues.

Still, the findings raise questions because “starting highly effective drugs early can prevent long-term disability,” said study lead author and neurologist Casey V. Farin, MD, a clinical fellow in the department of neurology at Duke University, Durham, N.C., who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers. “A lot of our general neurologists are prescribing the traditional platform therapies that have fallen a bit out of favor in the MS community,” she said.

Dr. Farin and colleagues launched their study to better understand whether “therapeutic inertia” is affecting how general neurologists treat MS. The term refers to “staying with one drug just because it is easier not to rock the boat,” she said. For the purposes of their study, the term encompasses reluctance of neurologists to escalate therapy or prescribe high-efficacy drugs.

“There have been small studies comparing subspecialists and general neurologists using surveys of theoretical cases,” she said. “No studies have looked at how people are prescribing disease-modifying therapy.”

In the new age of high-efficacy treatment, guidelines about early MS treatment are lacking. As the study abstract notes, “in the absence of robust head-to-head clinical data, neurologists do not have an accepted algorithm for initiation and escalation of therapy, although recent research indicates a benefit in initiating highly effective therapies early in the disease course.”

For the study, researchers tracked 4,753 patients with MS who were treated at the Duke University Health System from 2016 to 2018.

General neurologists prescribed platform therapies – interferons, glatiramer acetate (Copaxone) and dimethyl fumarate (Tecfidera) more often than did MS subspecialists (16% vs. 5%, P less than .0001, 12% vs. 6%, P = .001 and 31% vs. 11%, P less than .0001, respectively).

In regard to high-efficacy MS drugs, there was no significant difference in prescription rates of fingolimod (Gilenya) and natalizumab (Tysabri). But general neurologists were less likely to prescribe three other types than were general neurologists: Alemtuzumab (Lemtrada), ocrelizumab (Ocrevus) and rituximab (Rituxan) (0 vs. 8%, P = .0001, 3% vs. 27%, P less than .0001, and 2% vs. 7%, P = .0001, respectively).

Why might general neurologists be more resistant to embrace high-efficacy MS drugs? “They are newer and seen as more aggressive, and riskier,” Dr. Farin said. If general neurologists are not seeing many patients with MS and not prescribing these newer drugs very often, they may be more familiar with the older platform drugs, she said. “They may start with the ones that seem safer and are easier to start with.”

It is possible, she cautioned, that the study results may be confounded by general neurologists who refer patients to MS subspecialists when initial disease-modifying therapies fail.

No study funding was reported. Dr. Farin and two of the other four authors disclosed consulting fees from Biogen. No other disclosures were reported.

SOURCE: Farin CV et al. CMSC 2019. Abstract DXT44.

SEATTLE – Neurologists who subspecialize in multiple sclerosis (MS) are more likely than are general neurologists to prescribe three out of five high-efficacy medications for patients with the condition, according to the findings from a single-system study. It is not clear if the greater reluctance among general neurologists to prescribe the drugs is hurting the health of patients, and the study does not examine whether general neurologists are referring their toughest patients to their subspecialist colleagues.

Still, the findings raise questions because “starting highly effective drugs early can prevent long-term disability,” said study lead author and neurologist Casey V. Farin, MD, a clinical fellow in the department of neurology at Duke University, Durham, N.C., who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers. “A lot of our general neurologists are prescribing the traditional platform therapies that have fallen a bit out of favor in the MS community,” she said.

Dr. Farin and colleagues launched their study to better understand whether “therapeutic inertia” is affecting how general neurologists treat MS. The term refers to “staying with one drug just because it is easier not to rock the boat,” she said. For the purposes of their study, the term encompasses reluctance of neurologists to escalate therapy or prescribe high-efficacy drugs.

“There have been small studies comparing subspecialists and general neurologists using surveys of theoretical cases,” she said. “No studies have looked at how people are prescribing disease-modifying therapy.”

In the new age of high-efficacy treatment, guidelines about early MS treatment are lacking. As the study abstract notes, “in the absence of robust head-to-head clinical data, neurologists do not have an accepted algorithm for initiation and escalation of therapy, although recent research indicates a benefit in initiating highly effective therapies early in the disease course.”

For the study, researchers tracked 4,753 patients with MS who were treated at the Duke University Health System from 2016 to 2018.

General neurologists prescribed platform therapies – interferons, glatiramer acetate (Copaxone) and dimethyl fumarate (Tecfidera) more often than did MS subspecialists (16% vs. 5%, P less than .0001, 12% vs. 6%, P = .001 and 31% vs. 11%, P less than .0001, respectively).

In regard to high-efficacy MS drugs, there was no significant difference in prescription rates of fingolimod (Gilenya) and natalizumab (Tysabri). But general neurologists were less likely to prescribe three other types than were general neurologists: Alemtuzumab (Lemtrada), ocrelizumab (Ocrevus) and rituximab (Rituxan) (0 vs. 8%, P = .0001, 3% vs. 27%, P less than .0001, and 2% vs. 7%, P = .0001, respectively).

Why might general neurologists be more resistant to embrace high-efficacy MS drugs? “They are newer and seen as more aggressive, and riskier,” Dr. Farin said. If general neurologists are not seeing many patients with MS and not prescribing these newer drugs very often, they may be more familiar with the older platform drugs, she said. “They may start with the ones that seem safer and are easier to start with.”

It is possible, she cautioned, that the study results may be confounded by general neurologists who refer patients to MS subspecialists when initial disease-modifying therapies fail.

No study funding was reported. Dr. Farin and two of the other four authors disclosed consulting fees from Biogen. No other disclosures were reported.

SOURCE: Farin CV et al. CMSC 2019. Abstract DXT44.

SEATTLE – Neurologists who subspecialize in multiple sclerosis (MS) are more likely than are general neurologists to prescribe three out of five high-efficacy medications for patients with the condition, according to the findings from a single-system study. It is not clear if the greater reluctance among general neurologists to prescribe the drugs is hurting the health of patients, and the study does not examine whether general neurologists are referring their toughest patients to their subspecialist colleagues.

Still, the findings raise questions because “starting highly effective drugs early can prevent long-term disability,” said study lead author and neurologist Casey V. Farin, MD, a clinical fellow in the department of neurology at Duke University, Durham, N.C., who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers. “A lot of our general neurologists are prescribing the traditional platform therapies that have fallen a bit out of favor in the MS community,” she said.

Dr. Farin and colleagues launched their study to better understand whether “therapeutic inertia” is affecting how general neurologists treat MS. The term refers to “staying with one drug just because it is easier not to rock the boat,” she said. For the purposes of their study, the term encompasses reluctance of neurologists to escalate therapy or prescribe high-efficacy drugs.

“There have been small studies comparing subspecialists and general neurologists using surveys of theoretical cases,” she said. “No studies have looked at how people are prescribing disease-modifying therapy.”

In the new age of high-efficacy treatment, guidelines about early MS treatment are lacking. As the study abstract notes, “in the absence of robust head-to-head clinical data, neurologists do not have an accepted algorithm for initiation and escalation of therapy, although recent research indicates a benefit in initiating highly effective therapies early in the disease course.”

For the study, researchers tracked 4,753 patients with MS who were treated at the Duke University Health System from 2016 to 2018.

General neurologists prescribed platform therapies – interferons, glatiramer acetate (Copaxone) and dimethyl fumarate (Tecfidera) more often than did MS subspecialists (16% vs. 5%, P less than .0001, 12% vs. 6%, P = .001 and 31% vs. 11%, P less than .0001, respectively).

In regard to high-efficacy MS drugs, there was no significant difference in prescription rates of fingolimod (Gilenya) and natalizumab (Tysabri). But general neurologists were less likely to prescribe three other types than were general neurologists: Alemtuzumab (Lemtrada), ocrelizumab (Ocrevus) and rituximab (Rituxan) (0 vs. 8%, P = .0001, 3% vs. 27%, P less than .0001, and 2% vs. 7%, P = .0001, respectively).

Why might general neurologists be more resistant to embrace high-efficacy MS drugs? “They are newer and seen as more aggressive, and riskier,” Dr. Farin said. If general neurologists are not seeing many patients with MS and not prescribing these newer drugs very often, they may be more familiar with the older platform drugs, she said. “They may start with the ones that seem safer and are easier to start with.”

It is possible, she cautioned, that the study results may be confounded by general neurologists who refer patients to MS subspecialists when initial disease-modifying therapies fail.

No study funding was reported. Dr. Farin and two of the other four authors disclosed consulting fees from Biogen. No other disclosures were reported.

SOURCE: Farin CV et al. CMSC 2019. Abstract DXT44.

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.

As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.

Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.

Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
 

[email protected]

SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.

As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.

Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.

Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
 

[email protected]

SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.

As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.

Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.

Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
 

[email protected]

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

Among adults aged over age 65 years, taking a statin within 90 days after a concussion was associated with a 13% reduced risk of developing dementia in the subsequent 5 years, compared with similar adults not taking statins.

The findings come from a population-based double cohort study of 28,815 patients in the Ontario Health Insurance Plan. Study patients were enrolled over 20 years, and had a minimum follow-up of 3 years. The study excluded patients hospitalized caused by a severe concussion, those previously diagnosed with delirium or dementia, and those who died within 90 days of their concussions.

Concussions are a common injury in older adults and dementia may be a frequent outcome years afterward, Donald A. Redelmeier, MD, of the University of Toronto and colleagues wrote in a study published in JAMA Neurology. A concussion should not be interpreted as a reason to stop statins, and a potential neuroprotective benefit may encourage medication adherence among patients who are already prescribed a statin.

Of the 28,815 patients studied, 4,727 patients (1 case per 6 patients) developed dementia over the mean follow-up period of 3.9 years. The 7,058 patients who received a statin had a 13% reduced risk of developing dementia, compared with the 21,757 patients who did not (relative risk, 0.87; 95% confidence interval, 0.81-0.93; P less than .001).

Even though statin use was associated with a lower risk, the subsequent incidence of dementia was still twice the population norm in statin users who had concussions, the researchers wrote. The findings indicate concussions are a common injury in older adults and dementia may be a frequent outcome years after concussions.

Statin users who had concussions continued to have a reduced risk of developing dementia after adjustment for patient characteristics, use of other cardiovascular medications, dosage, and depression risk. The statin associated with the greatest risk reduction was rosuvastatin; simvastatin was associated with the least risk reduction. With the possible exception of angiotensin II receptor blockers, no other cardiovascular or noncardiovascular medications were associated with a decreased risk of dementia after a concussion, the researchers wrote.

They also examined data for elderly patients using statins after an ankle sprain and found the risk of dementia was similar for those who did and did not receive statins after the injury.

Factors such as smoking status, exercise, drug adherence, and other unknown aspects of patient health might have influenced the results of the study, the researchers acknowledged. Additionally, a secondary analysis was not statistically powered to distinguish the relative efficacy of statin use before a concussion.

This study was funded in part by a Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, the BrightFocus Foundation, and the Comprehensive Research Experience for Medical Students at the University of Toronto. The authors reported no relevant conflicts of interest.

SOURCE: Redelmeier DA et al. JAMA Neurol. 2019 May 20. doi: 10.1001/jamaneurol.2019.1148.

Among adults aged over age 65 years, taking a statin within 90 days after a concussion was associated with a 13% reduced risk of developing dementia in the subsequent 5 years, compared with similar adults not taking statins.

The findings come from a population-based double cohort study of 28,815 patients in the Ontario Health Insurance Plan. Study patients were enrolled over 20 years, and had a minimum follow-up of 3 years. The study excluded patients hospitalized caused by a severe concussion, those previously diagnosed with delirium or dementia, and those who died within 90 days of their concussions.

Concussions are a common injury in older adults and dementia may be a frequent outcome years afterward, Donald A. Redelmeier, MD, of the University of Toronto and colleagues wrote in a study published in JAMA Neurology. A concussion should not be interpreted as a reason to stop statins, and a potential neuroprotective benefit may encourage medication adherence among patients who are already prescribed a statin.

Of the 28,815 patients studied, 4,727 patients (1 case per 6 patients) developed dementia over the mean follow-up period of 3.9 years. The 7,058 patients who received a statin had a 13% reduced risk of developing dementia, compared with the 21,757 patients who did not (relative risk, 0.87; 95% confidence interval, 0.81-0.93; P less than .001).

Even though statin use was associated with a lower risk, the subsequent incidence of dementia was still twice the population norm in statin users who had concussions, the researchers wrote. The findings indicate concussions are a common injury in older adults and dementia may be a frequent outcome years after concussions.

Statin users who had concussions continued to have a reduced risk of developing dementia after adjustment for patient characteristics, use of other cardiovascular medications, dosage, and depression risk. The statin associated with the greatest risk reduction was rosuvastatin; simvastatin was associated with the least risk reduction. With the possible exception of angiotensin II receptor blockers, no other cardiovascular or noncardiovascular medications were associated with a decreased risk of dementia after a concussion, the researchers wrote.

They also examined data for elderly patients using statins after an ankle sprain and found the risk of dementia was similar for those who did and did not receive statins after the injury.

Factors such as smoking status, exercise, drug adherence, and other unknown aspects of patient health might have influenced the results of the study, the researchers acknowledged. Additionally, a secondary analysis was not statistically powered to distinguish the relative efficacy of statin use before a concussion.

This study was funded in part by a Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, the BrightFocus Foundation, and the Comprehensive Research Experience for Medical Students at the University of Toronto. The authors reported no relevant conflicts of interest.

SOURCE: Redelmeier DA et al. JAMA Neurol. 2019 May 20. doi: 10.1001/jamaneurol.2019.1148.

Among adults aged over age 65 years, taking a statin within 90 days after a concussion was associated with a 13% reduced risk of developing dementia in the subsequent 5 years, compared with similar adults not taking statins.

The findings come from a population-based double cohort study of 28,815 patients in the Ontario Health Insurance Plan. Study patients were enrolled over 20 years, and had a minimum follow-up of 3 years. The study excluded patients hospitalized caused by a severe concussion, those previously diagnosed with delirium or dementia, and those who died within 90 days of their concussions.

Concussions are a common injury in older adults and dementia may be a frequent outcome years afterward, Donald A. Redelmeier, MD, of the University of Toronto and colleagues wrote in a study published in JAMA Neurology. A concussion should not be interpreted as a reason to stop statins, and a potential neuroprotective benefit may encourage medication adherence among patients who are already prescribed a statin.

Of the 28,815 patients studied, 4,727 patients (1 case per 6 patients) developed dementia over the mean follow-up period of 3.9 years. The 7,058 patients who received a statin had a 13% reduced risk of developing dementia, compared with the 21,757 patients who did not (relative risk, 0.87; 95% confidence interval, 0.81-0.93; P less than .001).

Even though statin use was associated with a lower risk, the subsequent incidence of dementia was still twice the population norm in statin users who had concussions, the researchers wrote. The findings indicate concussions are a common injury in older adults and dementia may be a frequent outcome years after concussions.

Statin users who had concussions continued to have a reduced risk of developing dementia after adjustment for patient characteristics, use of other cardiovascular medications, dosage, and depression risk. The statin associated with the greatest risk reduction was rosuvastatin; simvastatin was associated with the least risk reduction. With the possible exception of angiotensin II receptor blockers, no other cardiovascular or noncardiovascular medications were associated with a decreased risk of dementia after a concussion, the researchers wrote.

They also examined data for elderly patients using statins after an ankle sprain and found the risk of dementia was similar for those who did and did not receive statins after the injury.

Factors such as smoking status, exercise, drug adherence, and other unknown aspects of patient health might have influenced the results of the study, the researchers acknowledged. Additionally, a secondary analysis was not statistically powered to distinguish the relative efficacy of statin use before a concussion.

This study was funded in part by a Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, the BrightFocus Foundation, and the Comprehensive Research Experience for Medical Students at the University of Toronto. The authors reported no relevant conflicts of interest.

SOURCE: Redelmeier DA et al. JAMA Neurol. 2019 May 20. doi: 10.1001/jamaneurol.2019.1148.

SAN FRANCISCO – Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

SAN FRANCISCO – Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

SAN FRANCISCO – Patients taking antidepressants for anxiety disorders face a therapeutic dilemma when their anxiety goes into remission. Relapse is more likely in the absence of medication and, if they resume their antidepressant after relapse, some patients experience adverse events or drug resistance.

Jim Kling/MDedge News

“It’s important that we realize that anxiety disorders can be treated effectively in the short term, but it’s very difficult to treat them for the long term. We know that within a year, it’s better to continue the medication. There’s a lack of data to give evidence-based advice after 1 year,” Neeltje Batelaan, MD, PhD, a psychiatrist and senior researcher at VU University Medical Center, Amsterdam, said in an interview.

Dr. Batelaan moderated a session at the annual meeting of the American Psychiatric Association on discontinuation of antidepressant medications in these patients.

Anxiety disorders can often be successfully treated with antidepressants, but their adverse effects can become less tolerable over time, especially after patients go into remission. When patients begin treatment, they are willing to endure side effects in the service of resolving their symptoms. But when they go into remission, “they want to get on with their lives, so their sexual side effects or their weight gain rates a lot worse,” Dr. Batelaan said.

A meta-analysis of 28 studies, with follow-up periods ranging from 8 to 52 weeks, found that the anxiety relapse risk after discontinuation of antidepressants was 36.4%, compared with 16.4% in those who stayed on medication. Even continuing antidepressants isn’t completely protective, she noted. The study found a number needed to treat of five to prevent one relapse.

Researchers at the VU University Medical Center developed a cognitive-behavioral therapy (CBT) regimen aimed at reducing anxiety relapses. In their study, 87 patients with a remitted anxiety disorder who wanted to stop their antidepressants were randomized to do so either with or without CBT intervention.

Unfortunately, the study had to be stopped when an interim analysis showed a lack of efficacy. In fact, patients who received CBT actually had higher relapse rates. Surprisingly, just 37% of patients succeeded in completely discontinuing medication, which hints at the inherent challenges of the transition.

“Unfortunately, building a CBT relapse prevention did not come true, but we learned some valuable lessons that will guide further studies,” Willemijn Scholten, PhD, a postdoc researcher at VU University Medical Center, said during one of the presentations.

In his presentation, Anton (Ton) Van Balkom, MD, PhD, professor of psychiatry at VU University Medical Center, recounted the case of a woman who had been functioning well with an antidepressant but grew tired of the sexual side effects. She carefully discontinued her medication under his guidance, but in 2 months she experienced her first panic attack in 30 years. Reintroducing the medication failed to resolve the issue, and it took years of effort before cognitive behavioral therapy resulted in a remission.

Further, a meta-analysis of nine studies showed that 17% of patients with remitted anxiety who went off and then restarted their antidepressants experienced tachycardia.

To help reduce tachycardia, Dr. Van Balkom suggested alternative options to antidepressants in less-complicated patients with anxiety, and to anticipate long-term use of antidepressants once those medications are employed.

Dr. Batelaan agreed with that assessment, drawing an analogy with type 2 diabetes. “You first start with a diet, and advise the patient to lose weight, and then if that’s not successful you go to [medication] and you realize it’s lifelong. Maybe we have to differentiate antidepressant therapies and [not start them until necessary]. But if you have to start them, realize that there’s a difficult decision waiting ahead.”

TORONTO – High-intensity statin therapy was associated with markedly reduced rates of knee and hip replacement surgery for osteoarthritis or rheumatoid arthritis in a longitudinal cohort study comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.

“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.

She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.

Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.

The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.

Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.

A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.

“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.

He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.

It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.

“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”

That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.

She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).

On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).

Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.

[email protected]

SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.

TORONTO – High-intensity statin therapy was associated with markedly reduced rates of knee and hip replacement surgery for osteoarthritis or rheumatoid arthritis in a longitudinal cohort study comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.

“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.

She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.

Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.

The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.

Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.

A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.

“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.

He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.

It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.

“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”

That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.

She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).

On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).

Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.

[email protected]

SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.

TORONTO – High-intensity statin therapy was associated with markedly reduced rates of knee and hip replacement surgery for osteoarthritis or rheumatoid arthritis in a longitudinal cohort study comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.

“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.

She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.

Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.

The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.

Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.

A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.

“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.

He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.

It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.

“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”

That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.

She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).

On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).

Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.

[email protected]

SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.

Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.

Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.

Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.

More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.

[email protected]

Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.

Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.

Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.

More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.

[email protected]

Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.

Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.

Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.

More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.

[email protected]

Medicare spending on pharmaceuticals is projected to increase if the Centers for Medicare & Medicaid Services finalizes changes to drug rebates in the Medicare program.

Kenishirotie/Thinkstock

The Congressional Budget Office is estimating that Medicare spending would increase by $170 billion from 2020-2029 if the rebate rule goes into effect, according to a report released May 2.

The proposed rule, issued Jan. 31, would make it illegal for drug manufacturers to pay rebates to health plans and pharmacy benefit managers in return for better formulary placement. Instead of rebates, manufacturers could offer discounts directly to beneficiaries by lowering list prices or making a payment to the pharmacy for the full amount of the negotiated discount – a chargeback. Under the proposal, a beneficiary’s cost sharing would be based on the lower list price or the price after the chargeback.

The CBO’s projected spending increases are based on the assumption that manufacturers will withhold 15% of current-law rebates, as well as increases in federal subsidies for premiums, changes in annual thresholds to beneficiary cost sharing, and the cost of implementing the chargeback system.

The agency expects premiums to rise, as many plans currently use the rebates they receive from drug companies to lower premiums across the board.

However, some beneficiaries “would pay lower prices on their prescription drugs, and for some beneficiaries, those reductions would be greater than their premium increases,” the CBO stated in its report. For beneficiaries who use few drugs or who use drugs that have no significant rebates, “the premium increase would outweigh the price reduction.”

Another reason federal spending would increase under this proposal is an expected increase in utilization that would come with the lowering of prices.

“In CBO’s estimate, the additional Part D utilization stemming from implementing the proposed rule would increase federal spending for beneficiaries who are not enrolled in the low-income subsidy program over the 2020-2029 period by a total of about 2% or $10 billion,” the report noted.

But the increase in utilization would have a net positive effect on Medicare spending for this population, as more beneficiaries followed their drug regimens resulting in lower spending for physician and hospital services under Medicare Part A and Part B by an estimated $20 billion over the same period, according to the CBO.

“On net, those effects are projected to reduce Medicare spending by $10 billion over the 2020-2029 period,” according to the report.

[email protected]

Medicare spending on pharmaceuticals is projected to increase if the Centers for Medicare & Medicaid Services finalizes changes to drug rebates in the Medicare program.

Kenishirotie/Thinkstock

The Congressional Budget Office is estimating that Medicare spending would increase by $170 billion from 2020-2029 if the rebate rule goes into effect, according to a report released May 2.

The proposed rule, issued Jan. 31, would make it illegal for drug manufacturers to pay rebates to health plans and pharmacy benefit managers in return for better formulary placement. Instead of rebates, manufacturers could offer discounts directly to beneficiaries by lowering list prices or making a payment to the pharmacy for the full amount of the negotiated discount – a chargeback. Under the proposal, a beneficiary’s cost sharing would be based on the lower list price or the price after the chargeback.

The CBO’s projected spending increases are based on the assumption that manufacturers will withhold 15% of current-law rebates, as well as increases in federal subsidies for premiums, changes in annual thresholds to beneficiary cost sharing, and the cost of implementing the chargeback system.

The agency expects premiums to rise, as many plans currently use the rebates they receive from drug companies to lower premiums across the board.

However, some beneficiaries “would pay lower prices on their prescription drugs, and for some beneficiaries, those reductions would be greater than their premium increases,” the CBO stated in its report. For beneficiaries who use few drugs or who use drugs that have no significant rebates, “the premium increase would outweigh the price reduction.”

Another reason federal spending would increase under this proposal is an expected increase in utilization that would come with the lowering of prices.

“In CBO’s estimate, the additional Part D utilization stemming from implementing the proposed rule would increase federal spending for beneficiaries who are not enrolled in the low-income subsidy program over the 2020-2029 period by a total of about 2% or $10 billion,” the report noted.

But the increase in utilization would have a net positive effect on Medicare spending for this population, as more beneficiaries followed their drug regimens resulting in lower spending for physician and hospital services under Medicare Part A and Part B by an estimated $20 billion over the same period, according to the CBO.

“On net, those effects are projected to reduce Medicare spending by $10 billion over the 2020-2029 period,” according to the report.

[email protected]

Medicare spending on pharmaceuticals is projected to increase if the Centers for Medicare & Medicaid Services finalizes changes to drug rebates in the Medicare program.

Kenishirotie/Thinkstock

The Congressional Budget Office is estimating that Medicare spending would increase by $170 billion from 2020-2029 if the rebate rule goes into effect, according to a report released May 2.

The proposed rule, issued Jan. 31, would make it illegal for drug manufacturers to pay rebates to health plans and pharmacy benefit managers in return for better formulary placement. Instead of rebates, manufacturers could offer discounts directly to beneficiaries by lowering list prices or making a payment to the pharmacy for the full amount of the negotiated discount – a chargeback. Under the proposal, a beneficiary’s cost sharing would be based on the lower list price or the price after the chargeback.

The CBO’s projected spending increases are based on the assumption that manufacturers will withhold 15% of current-law rebates, as well as increases in federal subsidies for premiums, changes in annual thresholds to beneficiary cost sharing, and the cost of implementing the chargeback system.

The agency expects premiums to rise, as many plans currently use the rebates they receive from drug companies to lower premiums across the board.

However, some beneficiaries “would pay lower prices on their prescription drugs, and for some beneficiaries, those reductions would be greater than their premium increases,” the CBO stated in its report. For beneficiaries who use few drugs or who use drugs that have no significant rebates, “the premium increase would outweigh the price reduction.”

Another reason federal spending would increase under this proposal is an expected increase in utilization that would come with the lowering of prices.

“In CBO’s estimate, the additional Part D utilization stemming from implementing the proposed rule would increase federal spending for beneficiaries who are not enrolled in the low-income subsidy program over the 2020-2029 period by a total of about 2% or $10 billion,” the report noted.

But the increase in utilization would have a net positive effect on Medicare spending for this population, as more beneficiaries followed their drug regimens resulting in lower spending for physician and hospital services under Medicare Part A and Part B by an estimated $20 billion over the same period, according to the CBO.

“On net, those effects are projected to reduce Medicare spending by $10 billion over the 2020-2029 period,” according to the report.

[email protected]

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.