Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST^® reinforce pulmonary rehabilitation’s benefits for this population.

A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.

“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.

The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
 

Study details

Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.

While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.

Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
 

Benefits of rehabilitation

Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.

“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”

These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.

This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).

Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST^® reinforce pulmonary rehabilitation’s benefits for this population.

A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.

“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.

The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
 

Study details

Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.

While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.

Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
 

Benefits of rehabilitation

Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.

“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”

These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.

This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).

Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST^® reinforce pulmonary rehabilitation’s benefits for this population.

A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.

“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.

The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
 

Study details

Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.

While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.

Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
 

Benefits of rehabilitation

Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.

“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”

These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.

This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

As 2021 winds down, I reflect on the achievements the rheumatology community has had in the realm of advocacy throughout the year. And there were many: Seven states signed accumulator program bans into law, five states reformed the use of step therapy protocols, Texas passed an innovative “gold carding” law to reduce the burden of prior authorization, and West Virginia passed a rebate pass-through law to directly assist patients with high out-of-pocket costs – the first of its kind in the nation.

Of course, the close of another year also means gearing up for the year ahead. The majority of state legislatures are getting ready to open legislative sessions in the New Year. This means a year of new opportunities and new challenges. As a community, there are some key areas rheumatology will need to focus on during the course of the upcoming year as policy makers return to the business of policy making.

Many in the rheumatology community are aware that the buy and bill acquisition system has come under threat in recent years, mainly from payer mandates to use the alternative white bagging model. In some cases, payers have gone as far as to mandate the practice of “brown bagging,” or home infusion. These practices can endanger patient safety and overall quality of care. A study led by Matthew Baker, MD, of Stanford (Calif.) University found that biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care; specifically, home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after infusion, compared with facility infusions, and 28% increased odds of permanent discontinuation of the biologic after emergency department or hospital admission. Additionally, site-of-care research by Paul Fronstin, PhD, at Employee Benefit Research Institute clearly shows that in-office infusion with physician supervision is far more cost effective than hospital and, in some cases, home infusion as well.

Further, the metastasis of these payer mandates is likely to severely limit availability of and access to care. It is unclear whether outpatient infusion, especially in private rheumatology practices, will prove sustainable in a world of white bagging. The net result of an expansion of the white-bagging requirements may well be broad access challenges that inconvenience patients deeply and irresponsibly.

The expansion of these mandates has not come without pushback, and rheumatologists should be prepared to advocate for policy that prohibits payers from mandating the use of white bagging, brown bagging, and home infusion. It is abundantly clear that arguments of safety and cost effectiveness are sufficient grounds for policy makers to curtail the mandatory use of these practices.

Similar to white bagging, another key issue in the year ahead is formulary construction based on the rebate system and proposed policies to address its attendant problems. Propagated by pharmacy benefit managers (PBMs), the rebate-based, or kickback, system of formulary construction often rewards higher-priced drugs with preferred placement regardless of whether they are the best and most affordable medications for our patients. A few states are beginning to address the affordability issue by mandating that the rebate/kickback acquired by the PBM be passed back to the patient at the point of sale. West Virginia passed a first-of-its-kind law to ensure that patients who generate drug rebates benefit from them by requiring that their cost shares are reduced by an amount equivalent to the rebate received by a health plan. This policy does not get at the root of the formulary construction problem, but if it is adopted more broadly across the country, it will deliver direct relief to patients who are struggling with out-of-pocket costs associated with prescription drugs. I anticipate that this will be a prominent issue nationwide during the upcoming year with opportunity for rheumatologists to lend their voices.

Many of the rheumatology community’s longstanding issues persist, and while progress has been made, more work remains to be done. Whether it’s accumulator programs, prior authorization, nonmedical switching, or step therapy, there will be opportunities in almost every state to engage in improving our ability to provide excellent care to our patients.

We tend to be motivated into action when one of these individual issues appear in our own state’s legislature; however, consistency of engagement is also important. While it is important to talk to your legislators when you need them to vote a certain way on a certain bill, scheduling a meeting with them or sending them a message detailing some of the issues that the rheumatology community faces before legislatures return in full swing is equally important to establish the relationship.

By making “rheum for action” now, you’ll have more impact when legislation relevant to our daily work does appear in the state legislatures. You can find your state representatives at the Coalition for State Rheumatology Organization’s Action Center.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

As 2021 winds down, I reflect on the achievements the rheumatology community has had in the realm of advocacy throughout the year. And there were many: Seven states signed accumulator program bans into law, five states reformed the use of step therapy protocols, Texas passed an innovative “gold carding” law to reduce the burden of prior authorization, and West Virginia passed a rebate pass-through law to directly assist patients with high out-of-pocket costs – the first of its kind in the nation.

Of course, the close of another year also means gearing up for the year ahead. The majority of state legislatures are getting ready to open legislative sessions in the New Year. This means a year of new opportunities and new challenges. As a community, there are some key areas rheumatology will need to focus on during the course of the upcoming year as policy makers return to the business of policy making.

Many in the rheumatology community are aware that the buy and bill acquisition system has come under threat in recent years, mainly from payer mandates to use the alternative white bagging model. In some cases, payers have gone as far as to mandate the practice of “brown bagging,” or home infusion. These practices can endanger patient safety and overall quality of care. A study led by Matthew Baker, MD, of Stanford (Calif.) University found that biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care; specifically, home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after infusion, compared with facility infusions, and 28% increased odds of permanent discontinuation of the biologic after emergency department or hospital admission. Additionally, site-of-care research by Paul Fronstin, PhD, at Employee Benefit Research Institute clearly shows that in-office infusion with physician supervision is far more cost effective than hospital and, in some cases, home infusion as well.

Further, the metastasis of these payer mandates is likely to severely limit availability of and access to care. It is unclear whether outpatient infusion, especially in private rheumatology practices, will prove sustainable in a world of white bagging. The net result of an expansion of the white-bagging requirements may well be broad access challenges that inconvenience patients deeply and irresponsibly.

The expansion of these mandates has not come without pushback, and rheumatologists should be prepared to advocate for policy that prohibits payers from mandating the use of white bagging, brown bagging, and home infusion. It is abundantly clear that arguments of safety and cost effectiveness are sufficient grounds for policy makers to curtail the mandatory use of these practices.

Similar to white bagging, another key issue in the year ahead is formulary construction based on the rebate system and proposed policies to address its attendant problems. Propagated by pharmacy benefit managers (PBMs), the rebate-based, or kickback, system of formulary construction often rewards higher-priced drugs with preferred placement regardless of whether they are the best and most affordable medications for our patients. A few states are beginning to address the affordability issue by mandating that the rebate/kickback acquired by the PBM be passed back to the patient at the point of sale. West Virginia passed a first-of-its-kind law to ensure that patients who generate drug rebates benefit from them by requiring that their cost shares are reduced by an amount equivalent to the rebate received by a health plan. This policy does not get at the root of the formulary construction problem, but if it is adopted more broadly across the country, it will deliver direct relief to patients who are struggling with out-of-pocket costs associated with prescription drugs. I anticipate that this will be a prominent issue nationwide during the upcoming year with opportunity for rheumatologists to lend their voices.

Many of the rheumatology community’s longstanding issues persist, and while progress has been made, more work remains to be done. Whether it’s accumulator programs, prior authorization, nonmedical switching, or step therapy, there will be opportunities in almost every state to engage in improving our ability to provide excellent care to our patients.

We tend to be motivated into action when one of these individual issues appear in our own state’s legislature; however, consistency of engagement is also important. While it is important to talk to your legislators when you need them to vote a certain way on a certain bill, scheduling a meeting with them or sending them a message detailing some of the issues that the rheumatology community faces before legislatures return in full swing is equally important to establish the relationship.

By making “rheum for action” now, you’ll have more impact when legislation relevant to our daily work does appear in the state legislatures. You can find your state representatives at the Coalition for State Rheumatology Organization’s Action Center.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

As 2021 winds down, I reflect on the achievements the rheumatology community has had in the realm of advocacy throughout the year. And there were many: Seven states signed accumulator program bans into law, five states reformed the use of step therapy protocols, Texas passed an innovative “gold carding” law to reduce the burden of prior authorization, and West Virginia passed a rebate pass-through law to directly assist patients with high out-of-pocket costs – the first of its kind in the nation.

Of course, the close of another year also means gearing up for the year ahead. The majority of state legislatures are getting ready to open legislative sessions in the New Year. This means a year of new opportunities and new challenges. As a community, there are some key areas rheumatology will need to focus on during the course of the upcoming year as policy makers return to the business of policy making.

Many in the rheumatology community are aware that the buy and bill acquisition system has come under threat in recent years, mainly from payer mandates to use the alternative white bagging model. In some cases, payers have gone as far as to mandate the practice of “brown bagging,” or home infusion. These practices can endanger patient safety and overall quality of care. A study led by Matthew Baker, MD, of Stanford (Calif.) University found that biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care; specifically, home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after infusion, compared with facility infusions, and 28% increased odds of permanent discontinuation of the biologic after emergency department or hospital admission. Additionally, site-of-care research by Paul Fronstin, PhD, at Employee Benefit Research Institute clearly shows that in-office infusion with physician supervision is far more cost effective than hospital and, in some cases, home infusion as well.

Further, the metastasis of these payer mandates is likely to severely limit availability of and access to care. It is unclear whether outpatient infusion, especially in private rheumatology practices, will prove sustainable in a world of white bagging. The net result of an expansion of the white-bagging requirements may well be broad access challenges that inconvenience patients deeply and irresponsibly.

The expansion of these mandates has not come without pushback, and rheumatologists should be prepared to advocate for policy that prohibits payers from mandating the use of white bagging, brown bagging, and home infusion. It is abundantly clear that arguments of safety and cost effectiveness are sufficient grounds for policy makers to curtail the mandatory use of these practices.

Similar to white bagging, another key issue in the year ahead is formulary construction based on the rebate system and proposed policies to address its attendant problems. Propagated by pharmacy benefit managers (PBMs), the rebate-based, or kickback, system of formulary construction often rewards higher-priced drugs with preferred placement regardless of whether they are the best and most affordable medications for our patients. A few states are beginning to address the affordability issue by mandating that the rebate/kickback acquired by the PBM be passed back to the patient at the point of sale. West Virginia passed a first-of-its-kind law to ensure that patients who generate drug rebates benefit from them by requiring that their cost shares are reduced by an amount equivalent to the rebate received by a health plan. This policy does not get at the root of the formulary construction problem, but if it is adopted more broadly across the country, it will deliver direct relief to patients who are struggling with out-of-pocket costs associated with prescription drugs. I anticipate that this will be a prominent issue nationwide during the upcoming year with opportunity for rheumatologists to lend their voices.

Many of the rheumatology community’s longstanding issues persist, and while progress has been made, more work remains to be done. Whether it’s accumulator programs, prior authorization, nonmedical switching, or step therapy, there will be opportunities in almost every state to engage in improving our ability to provide excellent care to our patients.

We tend to be motivated into action when one of these individual issues appear in our own state’s legislature; however, consistency of engagement is also important. While it is important to talk to your legislators when you need them to vote a certain way on a certain bill, scheduling a meeting with them or sending them a message detailing some of the issues that the rheumatology community faces before legislatures return in full swing is equally important to establish the relationship.

By making “rheum for action” now, you’ll have more impact when legislation relevant to our daily work does appear in the state legislatures. You can find your state representatives at the Coalition for State Rheumatology Organization’s Action Center.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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

The Food and Drug Administration has long kept a watchful eye over successive iterations of endovascular stent graphs in the Endologix AFX line, designed for repair of abdominal aortic aneurysms (AAA). For years, the devices, first approved in 2011, have drawn safety alerts and recalls , stemming from what the agency says was a “higher than expected” risk for potentially injurious or fatal type III endoleaks.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

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

The Food and Drug Administration has long kept a watchful eye over successive iterations of endovascular stent graphs in the Endologix AFX line, designed for repair of abdominal aortic aneurysms (AAA). For years, the devices, first approved in 2011, have drawn safety alerts and recalls , stemming from what the agency says was a “higher than expected” risk for potentially injurious or fatal type III endoleaks.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

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

The Food and Drug Administration has long kept a watchful eye over successive iterations of endovascular stent graphs in the Endologix AFX line, designed for repair of abdominal aortic aneurysms (AAA). For years, the devices, first approved in 2011, have drawn safety alerts and recalls , stemming from what the agency says was a “higher than expected” risk for potentially injurious or fatal type III endoleaks.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

Up to one-third of patients with multiple sclerosis (MS) treated with the B-cell depleting monoclonal antibody ocrelizumab (Ocrevus) show some degree of repletion of B-cells toward the end of the 6-month infusion cycle. However, there are no corresponding worsening of symptoms or signs of a “wearing off” effect, new research shows.

“Most people expect that since this is a B-cell depleting drug, that if you are not depleting B cells, then that should be reflected clinically and there should be some breakthrough activity,” said study investigator Joshua D. Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care in Wellesley, Massachusetts.

Real-world study

Preapproval clinical trials of ocrelizumab suggest about 5% of patients experience a repletion of B cells. However, the timing and association with breakthrough symptoms were unclear.

To investigate, Dr. Katz and colleagues conducted two studies. The first is a substudy of the prospective ACAPELLA trial to assess ocrelizumab-associated adverse events in a real-world population. The study included 294 patients with relapsing and progressive forms of MS treated with at least two cycles of ocrelizumab, given as infusion once every 6 months.

The results showed that overall, 91 (31%) of the 294 patients had some degree of repletion at one or more timepoints.

In categorizing patients according to their highest CD19 measure after two cycles, 108 patients (64.7%) had no significant repletion of B-cells after infusion, defined as an increase of less than 10 cells/μL, while 45 (26.9%) were considered mild repleters, defined as having increases of 10-49 cells/μL.

Seven patients (4.2%) were moderate repleters, with an increase of 50-79 cells/μL, and 7 (4.2%) were categorized as marked repleters, with increases of 80 or more cells/μL.

Eight patients in the study fully repleted, with values from 114-319 cells/μL, occurring between 23 and 34 weeks of the last infusion.

However, there was no relationship between repletion of the B-cells and clinical or MRI evidence of relapse.

Of note, the proportion of patients who did not have B-cell repletion increased with greater numbers of infusions. Whereas 64.7% were non-repleters at cycle 2, that number increased to 88.8% by cycle 6, with a slight drop to 85.6% being non-repleters by cycle 7 (36 months).

“Mild B-cell repletion was fairly common after two cycles of ocrelizumab, but with repeated dosing, a greater proportion of patients were non-repleters, suggesting that cumulative exposure to ocrelizumab results in greater depletion,” the researchers noted.

However, “while the number of moderate or marked repleters in our study was small, they had a tendency to remain repleters over time with subsequent infusions,” they added.

In looking at patient characteristics, moderate and marketed repleters had higher mean BMI (34.1 and 32.6, respectively) compared with the non- and mild repleters (27.0 and 29.4, respectively; P < .0001).

Dr. Katz noted that the increased risk of B-cell repletion with higher BMI was not a surprise. This association, he said, “makes sense” because patients’ relative exposure to ocrelizumab decreases with higher BMI. Similar patterns with BMI were observed in the clinical trial for ocrelizumab approval, in which patients with lower BMI tended to have greater improvement.
 

No symptom worsening

In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.

Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.

The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.

The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.

Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.

“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
 

Amplification of baseline symptoms not uncommon

Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.

“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”

“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.

The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.

“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.

As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.

Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The path to more effective use of clinical pathways in oncology practice lies in greater collaboration between the various sectors – oncology practices, payors, employers, pathways’ vendors, pharmaceutical manufacturers and patients – said Winston Wong, PharmD, president of W-Squared Group in Longboat Key, Fla., and editor-in-chief of the Journal of Clinical Pathways.

Dr. Wong presented findings from the journal’s annual Oncology Clinical Pathways Benchmarking Survey at the Oncology Clinical Pathways Congress, which was held in October. As fee for service gives way to performance-based and risk-bearing reimbursements, he said, “we are observing renewed interest in pathways implementation among a more diverse group of [health care providers].”

More survey respondents said they expected to implement pathways within the next 2 years than in past surveys. “I think it’s partly because payors are starting to delegate more care decisions back to oncology practices, making them more accountable for the care they provide,” Dr. Wong said.

The 2021 survey included 871 respondents, most of them direct care providers based in community practices. At 94%, most said they believed clinical pathways increased quality of care, 87% said they improved clinical outcomes, and 84% said they controlled costs.

Also presented at the meeting were preliminary findings of the JCP 2021 Care Pathways Working Group, which identified barriers to wider clinical pathways use. These include a fragmented health care system, minimal interoperability between systems, lack of integration into practice work flows, lack of reduction in administrative burden and lack of understanding by payers of the impact of social determinants of health.

Oncology clinical pathways are protocols and drug regimens for cancer care. They are used by oncology practices, academic medical centers, health systems, payors, and third-party vendors to address efficacy, safety, tolerability, and cost, but physicians have raised concerns about the administrative burden of working with pathways or pathways that emphasize cost-cutting at the expense of treatment choices or the flexibility to respond to unique patient circumstances.

The American Society of Clinical Oncology responded to member concerns about pathways in a 2016 Policy Statement on Clinical Pathways in Oncology. The following year, ASCO issued Criteria for High-Quality Clinical Pathways, offering a mechanism for evaluating the quality of a pathway, which according to ASCO’s criteria should be expert driven, evidence based, patient focused, up to date, and comprehensive, with multiple stakeholder input.

“There’s uncertainty among providers as the health care system continues to evolve toward value-based care models,” said Stephen Grubbs, MD, ASCO’s vice president of care delivery. “There are a lot of challenges. Practices are at different points in their journey toward value-based care and how to reconcile their care delivery models with the alternate payment models.”

Robin T. Zon, MD, FACP, FASCO, a medical oncologist at Michiana Hematology Oncology in Mishawaka, Ind., and chair of ASCO’s Pathways Task Force, which has since disbanded, was asked if she thought integration of pathways into practice has improved in the 4 years since the task force completed its work. “We think so, but we don’t have the data to support that conclusion,” she replied. “We were concerned about how we could make life easier for clinicians having to deal with preauthorization and helping them with the administrative burdens. Our society is trying to point to the path forward.”
 

Social determinants come to the fore

Also widely discussed at the congress was the need for greater equity in health care and greater responsiveness to social determinants of health, Dr. Wong said. Disparities in care are common throughout chronic disease care, and social determinants are getting more attention with the growing emphasis on patient-centered care.

Patient preferences and circumstances come into play, for example, when the patient can’t afford a prescribed treatment, or if a recommended protocol of infusions for 4 or 5 days in a row conflicts with the patient’s need to keep working. “If you don’t have a caregiver readily able to take you to the doctor’s office, that impacts your choice of treatment,” Dr. Wong said. Other social factors include geography, life experience, tolerance for side effects, and racial or ethnic diversity.

“I think the personalized approach is growing – compared to 4 or 5 years ago, when social determinants and patient preferences weren’t really talked about,” he said. How payors incorporate these considerations varies widely, but larger practices are starting to talk to payors about taking on financial risk, and clinical pathways can help them control risk and cost. “It has to be a collaborative process with whomever you’re talking to. The movement will be successful to the degree we collaborate in a common direction.”
 

Complicated treatments

Ray Page, DO, PhD, FASCO, a medical oncologist and hematologist at the Center for Cancer and Blood Disorders in Fort Worth, Tex., said his group has used clinical pathways, offered by Elsevier and originally developed at the University of Pittsburgh Medical Center, since 2007. “It’s part of the culture of our practice, and a requirement to work here. Cancer medicine is becoming so complicated, no oncologist can humanly keep track of it all. You’ve got to have good tools,” he said.

“Part of the nuance of dealing with insurers is that we’ve tried to negotiate using our compliance with evidence-based clinical pathways.” Collaboration is the ultimate goal, Dr. Page said. “But that gets harder as health care becomes more corporatized and vertically integrated.”

Alan Balch, PhD, CEO of the National Patient Advocate Foundation in Washington, D.C., said that well-designed pathways offer a way to ensure that evidence-based cancer care is practiced, and that providers are presented with a short list of treatment options based on evidence-based guidelines like those from the National Comprehensive Cancer Network.

“But if you want to be consumer centric, reflecting the circumstances of the individual patient, you either have to make your pathway more sophisticated and nuanced in the choices it offers – or see it as just one tool in treatment decision-making, while allowing other, patient-centered processes by which the patient’s circumstances and preferences are considered.” Is there a name for that process? “It’s called shared decision-making,” Dr. Balch replied.

“I’m optimistic that oncology care is becoming more person centered, whether by pathways or other means,” he said. “How long that will take, and in what form, is another conversation. But there is greater awareness of the need.”

People are talking to each other more about pathways implementation, Dr. Zon added. Pathways uptake will probably never be 100%, and the large academic medical centers will continue to have their own ways of caring for the sickest of the sick outside of the pathways.

Dr. Zon wondered if there could be a more comprehensive or universal oncology pathway incorporating symptom control, triaging, preventive screening, supportive and palliative care, and the end of life, all of which have fairly standardized approaches. “At the congress, I proposed thinking about a different approach for the pathways model – one that is not only more patient centric, but incorporates social determinants of health and patient experience, reflecting different cultures and communities, combining these other approaches to be more comprehensive and supporting best approaches to cancer care while reducing total costs of care.”

The path to more effective use of clinical pathways in oncology practice lies in greater collaboration between the various sectors – oncology practices, payors, employers, pathways’ vendors, pharmaceutical manufacturers and patients – said Winston Wong, PharmD, president of W-Squared Group in Longboat Key, Fla., and editor-in-chief of the Journal of Clinical Pathways.

Dr. Wong presented findings from the journal’s annual Oncology Clinical Pathways Benchmarking Survey at the Oncology Clinical Pathways Congress, which was held in October. As fee for service gives way to performance-based and risk-bearing reimbursements, he said, “we are observing renewed interest in pathways implementation among a more diverse group of [health care providers].”

More survey respondents said they expected to implement pathways within the next 2 years than in past surveys. “I think it’s partly because payors are starting to delegate more care decisions back to oncology practices, making them more accountable for the care they provide,” Dr. Wong said.

The 2021 survey included 871 respondents, most of them direct care providers based in community practices. At 94%, most said they believed clinical pathways increased quality of care, 87% said they improved clinical outcomes, and 84% said they controlled costs.

Also presented at the meeting were preliminary findings of the JCP 2021 Care Pathways Working Group, which identified barriers to wider clinical pathways use. These include a fragmented health care system, minimal interoperability between systems, lack of integration into practice work flows, lack of reduction in administrative burden and lack of understanding by payers of the impact of social determinants of health.

Oncology clinical pathways are protocols and drug regimens for cancer care. They are used by oncology practices, academic medical centers, health systems, payors, and third-party vendors to address efficacy, safety, tolerability, and cost, but physicians have raised concerns about the administrative burden of working with pathways or pathways that emphasize cost-cutting at the expense of treatment choices or the flexibility to respond to unique patient circumstances.

The American Society of Clinical Oncology responded to member concerns about pathways in a 2016 Policy Statement on Clinical Pathways in Oncology. The following year, ASCO issued Criteria for High-Quality Clinical Pathways, offering a mechanism for evaluating the quality of a pathway, which according to ASCO’s criteria should be expert driven, evidence based, patient focused, up to date, and comprehensive, with multiple stakeholder input.

“There’s uncertainty among providers as the health care system continues to evolve toward value-based care models,” said Stephen Grubbs, MD, ASCO’s vice president of care delivery. “There are a lot of challenges. Practices are at different points in their journey toward value-based care and how to reconcile their care delivery models with the alternate payment models.”

Robin T. Zon, MD, FACP, FASCO, a medical oncologist at Michiana Hematology Oncology in Mishawaka, Ind., and chair of ASCO’s Pathways Task Force, which has since disbanded, was asked if she thought integration of pathways into practice has improved in the 4 years since the task force completed its work. “We think so, but we don’t have the data to support that conclusion,” she replied. “We were concerned about how we could make life easier for clinicians having to deal with preauthorization and helping them with the administrative burdens. Our society is trying to point to the path forward.”
 

Social determinants come to the fore

Also widely discussed at the congress was the need for greater equity in health care and greater responsiveness to social determinants of health, Dr. Wong said. Disparities in care are common throughout chronic disease care, and social determinants are getting more attention with the growing emphasis on patient-centered care.

Patient preferences and circumstances come into play, for example, when the patient can’t afford a prescribed treatment, or if a recommended protocol of infusions for 4 or 5 days in a row conflicts with the patient’s need to keep working. “If you don’t have a caregiver readily able to take you to the doctor’s office, that impacts your choice of treatment,” Dr. Wong said. Other social factors include geography, life experience, tolerance for side effects, and racial or ethnic diversity.

“I think the personalized approach is growing – compared to 4 or 5 years ago, when social determinants and patient preferences weren’t really talked about,” he said. How payors incorporate these considerations varies widely, but larger practices are starting to talk to payors about taking on financial risk, and clinical pathways can help them control risk and cost. “It has to be a collaborative process with whomever you’re talking to. The movement will be successful to the degree we collaborate in a common direction.”
 

Complicated treatments

Ray Page, DO, PhD, FASCO, a medical oncologist and hematologist at the Center for Cancer and Blood Disorders in Fort Worth, Tex., said his group has used clinical pathways, offered by Elsevier and originally developed at the University of Pittsburgh Medical Center, since 2007. “It’s part of the culture of our practice, and a requirement to work here. Cancer medicine is becoming so complicated, no oncologist can humanly keep track of it all. You’ve got to have good tools,” he said.

“Part of the nuance of dealing with insurers is that we’ve tried to negotiate using our compliance with evidence-based clinical pathways.” Collaboration is the ultimate goal, Dr. Page said. “But that gets harder as health care becomes more corporatized and vertically integrated.”

Alan Balch, PhD, CEO of the National Patient Advocate Foundation in Washington, D.C., said that well-designed pathways offer a way to ensure that evidence-based cancer care is practiced, and that providers are presented with a short list of treatment options based on evidence-based guidelines like those from the National Comprehensive Cancer Network.

“But if you want to be consumer centric, reflecting the circumstances of the individual patient, you either have to make your pathway more sophisticated and nuanced in the choices it offers – or see it as just one tool in treatment decision-making, while allowing other, patient-centered processes by which the patient’s circumstances and preferences are considered.” Is there a name for that process? “It’s called shared decision-making,” Dr. Balch replied.

“I’m optimistic that oncology care is becoming more person centered, whether by pathways or other means,” he said. “How long that will take, and in what form, is another conversation. But there is greater awareness of the need.”

People are talking to each other more about pathways implementation, Dr. Zon added. Pathways uptake will probably never be 100%, and the large academic medical centers will continue to have their own ways of caring for the sickest of the sick outside of the pathways.

Dr. Zon wondered if there could be a more comprehensive or universal oncology pathway incorporating symptom control, triaging, preventive screening, supportive and palliative care, and the end of life, all of which have fairly standardized approaches. “At the congress, I proposed thinking about a different approach for the pathways model – one that is not only more patient centric, but incorporates social determinants of health and patient experience, reflecting different cultures and communities, combining these other approaches to be more comprehensive and supporting best approaches to cancer care while reducing total costs of care.”

The path to more effective use of clinical pathways in oncology practice lies in greater collaboration between the various sectors – oncology practices, payors, employers, pathways’ vendors, pharmaceutical manufacturers and patients – said Winston Wong, PharmD, president of W-Squared Group in Longboat Key, Fla., and editor-in-chief of the Journal of Clinical Pathways.

Dr. Wong presented findings from the journal’s annual Oncology Clinical Pathways Benchmarking Survey at the Oncology Clinical Pathways Congress, which was held in October. As fee for service gives way to performance-based and risk-bearing reimbursements, he said, “we are observing renewed interest in pathways implementation among a more diverse group of [health care providers].”

More survey respondents said they expected to implement pathways within the next 2 years than in past surveys. “I think it’s partly because payors are starting to delegate more care decisions back to oncology practices, making them more accountable for the care they provide,” Dr. Wong said.

The 2021 survey included 871 respondents, most of them direct care providers based in community practices. At 94%, most said they believed clinical pathways increased quality of care, 87% said they improved clinical outcomes, and 84% said they controlled costs.

Also presented at the meeting were preliminary findings of the JCP 2021 Care Pathways Working Group, which identified barriers to wider clinical pathways use. These include a fragmented health care system, minimal interoperability between systems, lack of integration into practice work flows, lack of reduction in administrative burden and lack of understanding by payers of the impact of social determinants of health.

Oncology clinical pathways are protocols and drug regimens for cancer care. They are used by oncology practices, academic medical centers, health systems, payors, and third-party vendors to address efficacy, safety, tolerability, and cost, but physicians have raised concerns about the administrative burden of working with pathways or pathways that emphasize cost-cutting at the expense of treatment choices or the flexibility to respond to unique patient circumstances.

The American Society of Clinical Oncology responded to member concerns about pathways in a 2016 Policy Statement on Clinical Pathways in Oncology. The following year, ASCO issued Criteria for High-Quality Clinical Pathways, offering a mechanism for evaluating the quality of a pathway, which according to ASCO’s criteria should be expert driven, evidence based, patient focused, up to date, and comprehensive, with multiple stakeholder input.

“There’s uncertainty among providers as the health care system continues to evolve toward value-based care models,” said Stephen Grubbs, MD, ASCO’s vice president of care delivery. “There are a lot of challenges. Practices are at different points in their journey toward value-based care and how to reconcile their care delivery models with the alternate payment models.”

Robin T. Zon, MD, FACP, FASCO, a medical oncologist at Michiana Hematology Oncology in Mishawaka, Ind., and chair of ASCO’s Pathways Task Force, which has since disbanded, was asked if she thought integration of pathways into practice has improved in the 4 years since the task force completed its work. “We think so, but we don’t have the data to support that conclusion,” she replied. “We were concerned about how we could make life easier for clinicians having to deal with preauthorization and helping them with the administrative burdens. Our society is trying to point to the path forward.”
 

Social determinants come to the fore

Also widely discussed at the congress was the need for greater equity in health care and greater responsiveness to social determinants of health, Dr. Wong said. Disparities in care are common throughout chronic disease care, and social determinants are getting more attention with the growing emphasis on patient-centered care.

Patient preferences and circumstances come into play, for example, when the patient can’t afford a prescribed treatment, or if a recommended protocol of infusions for 4 or 5 days in a row conflicts with the patient’s need to keep working. “If you don’t have a caregiver readily able to take you to the doctor’s office, that impacts your choice of treatment,” Dr. Wong said. Other social factors include geography, life experience, tolerance for side effects, and racial or ethnic diversity.

“I think the personalized approach is growing – compared to 4 or 5 years ago, when social determinants and patient preferences weren’t really talked about,” he said. How payors incorporate these considerations varies widely, but larger practices are starting to talk to payors about taking on financial risk, and clinical pathways can help them control risk and cost. “It has to be a collaborative process with whomever you’re talking to. The movement will be successful to the degree we collaborate in a common direction.”
 

Complicated treatments

Ray Page, DO, PhD, FASCO, a medical oncologist and hematologist at the Center for Cancer and Blood Disorders in Fort Worth, Tex., said his group has used clinical pathways, offered by Elsevier and originally developed at the University of Pittsburgh Medical Center, since 2007. “It’s part of the culture of our practice, and a requirement to work here. Cancer medicine is becoming so complicated, no oncologist can humanly keep track of it all. You’ve got to have good tools,” he said.

“Part of the nuance of dealing with insurers is that we’ve tried to negotiate using our compliance with evidence-based clinical pathways.” Collaboration is the ultimate goal, Dr. Page said. “But that gets harder as health care becomes more corporatized and vertically integrated.”

Alan Balch, PhD, CEO of the National Patient Advocate Foundation in Washington, D.C., said that well-designed pathways offer a way to ensure that evidence-based cancer care is practiced, and that providers are presented with a short list of treatment options based on evidence-based guidelines like those from the National Comprehensive Cancer Network.

“But if you want to be consumer centric, reflecting the circumstances of the individual patient, you either have to make your pathway more sophisticated and nuanced in the choices it offers – or see it as just one tool in treatment decision-making, while allowing other, patient-centered processes by which the patient’s circumstances and preferences are considered.” Is there a name for that process? “It’s called shared decision-making,” Dr. Balch replied.

“I’m optimistic that oncology care is becoming more person centered, whether by pathways or other means,” he said. “How long that will take, and in what form, is another conversation. But there is greater awareness of the need.”

People are talking to each other more about pathways implementation, Dr. Zon added. Pathways uptake will probably never be 100%, and the large academic medical centers will continue to have their own ways of caring for the sickest of the sick outside of the pathways.

Dr. Zon wondered if there could be a more comprehensive or universal oncology pathway incorporating symptom control, triaging, preventive screening, supportive and palliative care, and the end of life, all of which have fairly standardized approaches. “At the congress, I proposed thinking about a different approach for the pathways model – one that is not only more patient centric, but incorporates social determinants of health and patient experience, reflecting different cultures and communities, combining these other approaches to be more comprehensive and supporting best approaches to cancer care while reducing total costs of care.”

LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.

The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.

Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.

The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm² protein and < 2.2 mcg/cm² carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.

The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.

In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm², versus 0.16 mcg/cm² in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm² and 0.14 mcg/cm², respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
 

Removing variability from cleaning

The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.

The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.

“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.

He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.

Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.

Dr. O’Donnell and Dr. Young have no relevant financial disclosures.

LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.

The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.

Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.

The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm² protein and < 2.2 mcg/cm² carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.

The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.

In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm², versus 0.16 mcg/cm² in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm² and 0.14 mcg/cm², respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
 

Removing variability from cleaning

The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.

The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.

“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.

He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.

Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.

Dr. O’Donnell and Dr. Young have no relevant financial disclosures.

LAS VEGAS – An automated cleaning system outperformed manual cleaning of duodenoscopes in a comparative study. The results included measurements of residual proteins and carbohydrates in all duodenoscope working channels and elevators.

The new automated cleaning system, called the MACH 1, can be added to existing reprocessing areas and is about the size of a commercial washing machine. Cleaning alone takes about 30 minutes, and clean plus high-level disinfection (HLD) takes about an hour, according to Michael O’Donnell, MD, who is a gastroenterology fellow at NYU Langone Health. “Data from prior studies of other automated endoscope reprocessors indicate that MACH 1 more consistently delivers cleaning results that meet or exceed Food and Drug Administration/AAMI (Association for the Advancement of Medical Instrumentation) guidelines,” Dr. O’Donnell said in an interview. He presented the study at the annual meeting of the American College of Gastroenterology.

Outbreaks of multidrug resistant organism (MDRO) transmission have been linked to inadequately cleaned duodenoscopes, which has led to greater attention being paid to duodenoscope reprocessing, including prewash, manual cleaning, and disinfection or sterilization, according to Dr. O’Donnell. Postmarketing surveillance by duodenoscope manufacturers Fujifilm, Olympus, and Pentax found a contamination rate of 5.4% for any high-concern organisms – far higher than the initially assumed 0.4%.

The researchers used FDA standard maximum allowed contaminant threshold of < 6.4 mcg/cm² protein and < 2.2 mcg/cm² carbohydrate. Sampling sites on the duodenoscopes included the elevator wire channel port when present, the biopsy port, the elevator wire channel, the instrument channel, and the elevator recess.

The study included Olympic TJF-Q180V duodenoscopes used in 48 endoscopic retrograde cholangiopancreatography (ERCP) procedures. Each instrument went through standard bedside precleaning; 21 were then cleaned manually by trained technicians following manufacturing instructions, and 27 were cleaned using the automated cleaning system.

In the manually cleaned duodenoscopes, the average level of residual protein was 4.88 mcg/cm², versus 0.16 mcg/cm² in the automated clean group. The average carbohydrate residues were 1.09 mcg/cm² and 0.14 mcg/cm², respectively. In all, 2 of the 21 manually cleaned devices had protein levels higher than the FDA threshold, versus none in the automated clean group. In addition, 3 of 21 in the manually cleaned group had higher than threshold carbohydrate levels, versus none in the automated clean group. Overall, 4 of the 27 manually cleaned devices and none of the 21 automated clean devices had protein or carbohydrate levels above FDA thresholds.
 

Removing variability from cleaning

The cleaning step is critical because failure to remove bioburden can reduce the efficacy of later HLD or sterilization. Cleaning is typically done manually, but the physical complexity of the duodenoscope makes it challenging to do it thoroughly. Manual cleaning is also susceptible to human error or insufficient training, and an observational study found that at least one error occurred in more than 90% of observed cleaning operations.

The MACH 1 uses turbulent flow and resultant shearing forces to clean the duodenoscope. The device is currently used at the medical device company Parametrik as part of a program that delivers clean duodenoscopes and ultrasound scopes to its customers. The service is currently available only in the New York metro area, but the company intends to expand to other cities in 2022. The company also has plans to sell the MACH 1 in the near future at prices comparable to automated endoscope reprocessors that don’t clean, according to Dr. O’Donnell.

“This is a huge issue, not only practically for patient care, but it’s very much in the public eye. As people who do ERCP, this is a question that patients will come to us with, so we want to be as diligent as possible to drive the bioburden in the scope as low as we can. At least intuitively, that makes sense,” said Patrick Young, MD, who comoderated the session and is a professor of medicine at the Uniformed Services University, Bethesda, Md.

He noted that the system has an advantage in that it can be applied to duodenoscopes already in house. Other approaches to the issue of improperly cleaned duodenoscopes include scopes that can be returned to the manufacturer for cleaning, or removable end cap to facilitate access to difficult to clean parts. And then there are disposal duodenoscopes. “If you’re throwing a scope away every time you use it, you worry about landfill issues and some of the long term effects of that,” said Dr. Young.

Perhaps the most important attribute of the automated cleaning device is that it allows the user to eliminate variation in the cleaning procedure. High-reliability organizations aspire to eliminating variability. “This will probably make it easier to be consistent across technicians – for example, maybe there’s one tech that cleans great and one tech that doesn’t. This may take some of that out of the equation and give you a more thorough cleaning regardless of circumstance or personnel working on it. So I think it’s exciting to have another option that might be less costly than buying new scopes,” said Dr. Young.

Dr. O’Donnell and Dr. Young have no relevant financial disclosures.