EXPERT COMMENTARY

Main EK, Chang SC, Cape V, et al. Safety assessment of a large-scale improvement collaborative to reduce nulliparous cesarean delivery rates. Obstet Gynecol. 2019;133:613-623.

Cesarean delivery can be lifesaving for both mother and infant. When compared with successful vaginal delivery, however, CD is associated with higher maternal complication rates (including excessive blood loss requiring blood product transfusion, infectious morbidity, and venous thromboembolic events), longer hospital length of stay, and higher cost. While the optimal CD rate is not well defined, it is generally accepted that the CD rate in the United States is excessively high. As such, efforts to reduce the CD rate should be encouraged, but not at the expense of patient safety.

Details about the study

In keeping with the dictum that the most important CD to prevent is the first one, the California Maternal Quality Care Collaborative (CMQCC) in 2016 introduced a large-scale quality improvement project designed to reduce nulliparous, term, singleton, vertex (NTSV) CDs across the state. This bundle included education around joint guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine on reducing primary CDs,¹ introduction of a CMQCC toolkit, increased nursing labor support, and monthly meetings to share best practices across all collaborating sites. The NTSV CD rate in these hospitals did decrease from 29.3% in 2015 to 25.0% in 2017 (adjusted odds ratio, 0.76; 95% confidence interval, 0.73–0.78).

Whether or not implementation of the bundle resulted in an inappropriate delay in indicated CDs and, as such, in an increase in maternal or neonatal morbidity is not known. To address this issue, Main and colleagues collected cross-sectional data from more than 50 hospitals with more than 119,000 deliveries throughout California and measured rates of chorioamnionitis, blood transfusions, third- or fourth-degree perineal lacerations, operative vaginal delivery, severe unexpected newborn complications, and 5-minute Apgar scores of less than 5. None of the 6 safety measures showed any difference when comparing 2017 (after implementation of the CMQCC bundle) to 2015 (before implementation), suggesting that patient safety was not compromised significantly.

Study strengths and weaknesses

Strengths of this study include its large sample size and multicenter design with inclusion of a variety of collaborating hospitals. Earlier studies examining the effect of standardized protocols to reduce CD rates have been largely underpowered and conducted at single institutions.^2-6 Moreover, results have been mixed, with some studies reporting an increase in maternal/neonatal adverse events,^2-4 while others suggesting an improvement in select newborn quality outcome metrics.⁵ The current study provides reassurance to providers and institutions employing strategies to reduce NTSV CD rates that such efforts are safe.

Continue to: This study has several limitations...

This study has several limitations. Data collection relied on birth certificate and discharge diagnoses without a robust quality audit. As such, ascertainment bias, random error, and undercounting cannot be excluded. Although the population was heterogeneous, most women had more than a high school education and private insurance, and only 1 in 5 were obese. Whether these findings are generalizable to other areas within the United States is not known.

EXPERT COMMENTARY

Main EK, Chang SC, Cape V, et al. Safety assessment of a large-scale improvement collaborative to reduce nulliparous cesarean delivery rates. Obstet Gynecol. 2019;133:613-623.

Cesarean delivery can be lifesaving for both mother and infant. When compared with successful vaginal delivery, however, CD is associated with higher maternal complication rates (including excessive blood loss requiring blood product transfusion, infectious morbidity, and venous thromboembolic events), longer hospital length of stay, and higher cost. While the optimal CD rate is not well defined, it is generally accepted that the CD rate in the United States is excessively high. As such, efforts to reduce the CD rate should be encouraged, but not at the expense of patient safety.

Details about the study

In keeping with the dictum that the most important CD to prevent is the first one, the California Maternal Quality Care Collaborative (CMQCC) in 2016 introduced a large-scale quality improvement project designed to reduce nulliparous, term, singleton, vertex (NTSV) CDs across the state. This bundle included education around joint guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine on reducing primary CDs,¹ introduction of a CMQCC toolkit, increased nursing labor support, and monthly meetings to share best practices across all collaborating sites. The NTSV CD rate in these hospitals did decrease from 29.3% in 2015 to 25.0% in 2017 (adjusted odds ratio, 0.76; 95% confidence interval, 0.73–0.78).

Whether or not implementation of the bundle resulted in an inappropriate delay in indicated CDs and, as such, in an increase in maternal or neonatal morbidity is not known. To address this issue, Main and colleagues collected cross-sectional data from more than 50 hospitals with more than 119,000 deliveries throughout California and measured rates of chorioamnionitis, blood transfusions, third- or fourth-degree perineal lacerations, operative vaginal delivery, severe unexpected newborn complications, and 5-minute Apgar scores of less than 5. None of the 6 safety measures showed any difference when comparing 2017 (after implementation of the CMQCC bundle) to 2015 (before implementation), suggesting that patient safety was not compromised significantly.

Study strengths and weaknesses

Strengths of this study include its large sample size and multicenter design with inclusion of a variety of collaborating hospitals. Earlier studies examining the effect of standardized protocols to reduce CD rates have been largely underpowered and conducted at single institutions.^2-6 Moreover, results have been mixed, with some studies reporting an increase in maternal/neonatal adverse events,^2-4 while others suggesting an improvement in select newborn quality outcome metrics.⁵ The current study provides reassurance to providers and institutions employing strategies to reduce NTSV CD rates that such efforts are safe.

Continue to: This study has several limitations...

This study has several limitations. Data collection relied on birth certificate and discharge diagnoses without a robust quality audit. As such, ascertainment bias, random error, and undercounting cannot be excluded. Although the population was heterogeneous, most women had more than a high school education and private insurance, and only 1 in 5 were obese. Whether these findings are generalizable to other areas within the United States is not known.

EXPERT COMMENTARY

Main EK, Chang SC, Cape V, et al. Safety assessment of a large-scale improvement collaborative to reduce nulliparous cesarean delivery rates. Obstet Gynecol. 2019;133:613-623.

Cesarean delivery can be lifesaving for both mother and infant. When compared with successful vaginal delivery, however, CD is associated with higher maternal complication rates (including excessive blood loss requiring blood product transfusion, infectious morbidity, and venous thromboembolic events), longer hospital length of stay, and higher cost. While the optimal CD rate is not well defined, it is generally accepted that the CD rate in the United States is excessively high. As such, efforts to reduce the CD rate should be encouraged, but not at the expense of patient safety.

Details about the study

In keeping with the dictum that the most important CD to prevent is the first one, the California Maternal Quality Care Collaborative (CMQCC) in 2016 introduced a large-scale quality improvement project designed to reduce nulliparous, term, singleton, vertex (NTSV) CDs across the state. This bundle included education around joint guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine on reducing primary CDs,¹ introduction of a CMQCC toolkit, increased nursing labor support, and monthly meetings to share best practices across all collaborating sites. The NTSV CD rate in these hospitals did decrease from 29.3% in 2015 to 25.0% in 2017 (adjusted odds ratio, 0.76; 95% confidence interval, 0.73–0.78).

Whether or not implementation of the bundle resulted in an inappropriate delay in indicated CDs and, as such, in an increase in maternal or neonatal morbidity is not known. To address this issue, Main and colleagues collected cross-sectional data from more than 50 hospitals with more than 119,000 deliveries throughout California and measured rates of chorioamnionitis, blood transfusions, third- or fourth-degree perineal lacerations, operative vaginal delivery, severe unexpected newborn complications, and 5-minute Apgar scores of less than 5. None of the 6 safety measures showed any difference when comparing 2017 (after implementation of the CMQCC bundle) to 2015 (before implementation), suggesting that patient safety was not compromised significantly.

Study strengths and weaknesses

Strengths of this study include its large sample size and multicenter design with inclusion of a variety of collaborating hospitals. Earlier studies examining the effect of standardized protocols to reduce CD rates have been largely underpowered and conducted at single institutions.^2-6 Moreover, results have been mixed, with some studies reporting an increase in maternal/neonatal adverse events,^2-4 while others suggesting an improvement in select newborn quality outcome metrics.⁵ The current study provides reassurance to providers and institutions employing strategies to reduce NTSV CD rates that such efforts are safe.

Continue to: This study has several limitations...

This study has several limitations. Data collection relied on birth certificate and discharge diagnoses without a robust quality audit. As such, ascertainment bias, random error, and undercounting cannot be excluded. Although the population was heterogeneous, most women had more than a high school education and private insurance, and only 1 in 5 were obese. Whether these findings are generalizable to other areas within the United States is not known.

Hospitalists know that a small percentage of patients account for a disproportionately large percentage of overall health care spending, much of which comes from inpatient admissions. Many programs have been developed around the country to work with this population, and most of these programs are – appropriately – outpatient based. 

“However, a subset of frequently admitted patients either don’t make it to outpatient care or are unengaged with outpatient care and programs, for whom hospital stays can give us a unique opportunity to coordinate and streamline care, and to build trust that can then lead to increased patient engagement,” said Kirstin Knox, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, and lead author of an abstract describing a method to address this challenge. “Our program works with these patients, the ‘outliers among the outliers’ to re-engage them in care, streamline admissions, coordinate inpatient and outpatient care, and address the underlying barriers/drivers that lead to frequent hospitalization.”

Their program designed and implemented a multidisciplinary intervention targeting the highest utilizers on their inpatient general medicine service. Each was assigned an inpatient continuity team, and the patient case was then presented to a multidisciplinary high-utilizer care committee that included physicians, nurses, and social workers, as well as representatives from a community health worker program, home care, and risk management to develop a care plan.

Analysis comparing the 6 months before and after intervention showed admissions and total hospital days were reduced by 55% and 47% respectively, and 30-day readmissions were reduced by 65%. Total direct costs were reduced from $2,923,000 to $1,284,000.

The top takeaway, Dr. Knox said, is that, through efforts to coordinate care and address underlying drivers of high utilization, hospital-based programs for the most frequently admitted patients can streamline inpatient care and decrease utilization for many high-risk, high-cost patients.

“I hope that hospitalists will consider starting inpatient-based high-utilizer programs at their own institutions, if they haven’t already,” she said. “Even starting with one or two of your most frequently admitted patients can be incredibly eye opening, and streamlining/coordinating care (as well as working overtime to address the underlying drivers/barriers that lead to high utilization) for these patients is incredibly rewarding.”
 

Reference

Knox K et al. Breaking the cycle: a successful inpatient based intervention for hospital high utilizers. Abstract published at Hospital Medicine 2018; Apr 8-11; Orlando, Fla., Abstract 319. Accessed 2018 Oct 2.

Hospitalists know that a small percentage of patients account for a disproportionately large percentage of overall health care spending, much of which comes from inpatient admissions. Many programs have been developed around the country to work with this population, and most of these programs are – appropriately – outpatient based. 

“However, a subset of frequently admitted patients either don’t make it to outpatient care or are unengaged with outpatient care and programs, for whom hospital stays can give us a unique opportunity to coordinate and streamline care, and to build trust that can then lead to increased patient engagement,” said Kirstin Knox, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, and lead author of an abstract describing a method to address this challenge. “Our program works with these patients, the ‘outliers among the outliers’ to re-engage them in care, streamline admissions, coordinate inpatient and outpatient care, and address the underlying barriers/drivers that lead to frequent hospitalization.”

Their program designed and implemented a multidisciplinary intervention targeting the highest utilizers on their inpatient general medicine service. Each was assigned an inpatient continuity team, and the patient case was then presented to a multidisciplinary high-utilizer care committee that included physicians, nurses, and social workers, as well as representatives from a community health worker program, home care, and risk management to develop a care plan.

Analysis comparing the 6 months before and after intervention showed admissions and total hospital days were reduced by 55% and 47% respectively, and 30-day readmissions were reduced by 65%. Total direct costs were reduced from $2,923,000 to $1,284,000.

The top takeaway, Dr. Knox said, is that, through efforts to coordinate care and address underlying drivers of high utilization, hospital-based programs for the most frequently admitted patients can streamline inpatient care and decrease utilization for many high-risk, high-cost patients.

“I hope that hospitalists will consider starting inpatient-based high-utilizer programs at their own institutions, if they haven’t already,” she said. “Even starting with one or two of your most frequently admitted patients can be incredibly eye opening, and streamlining/coordinating care (as well as working overtime to address the underlying drivers/barriers that lead to high utilization) for these patients is incredibly rewarding.”
 

Reference

Knox K et al. Breaking the cycle: a successful inpatient based intervention for hospital high utilizers. Abstract published at Hospital Medicine 2018; Apr 8-11; Orlando, Fla., Abstract 319. Accessed 2018 Oct 2.

Hospitalists know that a small percentage of patients account for a disproportionately large percentage of overall health care spending, much of which comes from inpatient admissions. Many programs have been developed around the country to work with this population, and most of these programs are – appropriately – outpatient based. 

“However, a subset of frequently admitted patients either don’t make it to outpatient care or are unengaged with outpatient care and programs, for whom hospital stays can give us a unique opportunity to coordinate and streamline care, and to build trust that can then lead to increased patient engagement,” said Kirstin Knox, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, and lead author of an abstract describing a method to address this challenge. “Our program works with these patients, the ‘outliers among the outliers’ to re-engage them in care, streamline admissions, coordinate inpatient and outpatient care, and address the underlying barriers/drivers that lead to frequent hospitalization.”

Their program designed and implemented a multidisciplinary intervention targeting the highest utilizers on their inpatient general medicine service. Each was assigned an inpatient continuity team, and the patient case was then presented to a multidisciplinary high-utilizer care committee that included physicians, nurses, and social workers, as well as representatives from a community health worker program, home care, and risk management to develop a care plan.

Analysis comparing the 6 months before and after intervention showed admissions and total hospital days were reduced by 55% and 47% respectively, and 30-day readmissions were reduced by 65%. Total direct costs were reduced from $2,923,000 to $1,284,000.

The top takeaway, Dr. Knox said, is that, through efforts to coordinate care and address underlying drivers of high utilization, hospital-based programs for the most frequently admitted patients can streamline inpatient care and decrease utilization for many high-risk, high-cost patients.

“I hope that hospitalists will consider starting inpatient-based high-utilizer programs at their own institutions, if they haven’t already,” she said. “Even starting with one or two of your most frequently admitted patients can be incredibly eye opening, and streamlining/coordinating care (as well as working overtime to address the underlying drivers/barriers that lead to high utilization) for these patients is incredibly rewarding.”
 

Reference

Knox K et al. Breaking the cycle: a successful inpatient based intervention for hospital high utilizers. Abstract published at Hospital Medicine 2018; Apr 8-11; Orlando, Fla., Abstract 319. Accessed 2018 Oct 2.

The FP was puzzled by the lack of response to treatment and decided to perform a 4-mm punch biopsy at the edge of the nonhealing ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). His differential diagnosis included pyoderma gangrenosum and a deep fungal infection. The pathologist called a week later FP with a surprising result: anaplastic large cell cutaneous T-cell lymphoma. (See the Watch & Learn video on “Punch biopsy.”) 

Anaplastic large cell cutaneous T-cell lymphoma is a rare diagnosis—especially in a teenager—and it can’t be determined by appearance only. On follow-up, the FP explained the diagnosis to the patient and her mother. He called Hematology/Oncology to facilitate the referral.

The patient was treated by the specialist with weekly oral methotrexate and her skin cleared up completely. Although she would likely need treatment for years, the prognosis was good. This case is a reminder that when a treatment is not working for an expected diagnosis, it’s time to reconsider the diagnosis and do further testing to identify the correct diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP was puzzled by the lack of response to treatment and decided to perform a 4-mm punch biopsy at the edge of the nonhealing ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). His differential diagnosis included pyoderma gangrenosum and a deep fungal infection. The pathologist called a week later FP with a surprising result: anaplastic large cell cutaneous T-cell lymphoma. (See the Watch & Learn video on “Punch biopsy.”) 

Anaplastic large cell cutaneous T-cell lymphoma is a rare diagnosis—especially in a teenager—and it can’t be determined by appearance only. On follow-up, the FP explained the diagnosis to the patient and her mother. He called Hematology/Oncology to facilitate the referral.

The patient was treated by the specialist with weekly oral methotrexate and her skin cleared up completely. Although she would likely need treatment for years, the prognosis was good. This case is a reminder that when a treatment is not working for an expected diagnosis, it’s time to reconsider the diagnosis and do further testing to identify the correct diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP was puzzled by the lack of response to treatment and decided to perform a 4-mm punch biopsy at the edge of the nonhealing ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). His differential diagnosis included pyoderma gangrenosum and a deep fungal infection. The pathologist called a week later FP with a surprising result: anaplastic large cell cutaneous T-cell lymphoma. (See the Watch & Learn video on “Punch biopsy.”) 

Anaplastic large cell cutaneous T-cell lymphoma is a rare diagnosis—especially in a teenager—and it can’t be determined by appearance only. On follow-up, the FP explained the diagnosis to the patient and her mother. He called Hematology/Oncology to facilitate the referral.

The patient was treated by the specialist with weekly oral methotrexate and her skin cleared up completely. Although she would likely need treatment for years, the prognosis was good. This case is a reminder that when a treatment is not working for an expected diagnosis, it’s time to reconsider the diagnosis and do further testing to identify the correct diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

MILWAUKEE – An interdisciplinary intensive outpatient treatment program addressing chronic pain and substance use disorder effectively addressed both diagnoses in a military population.

Kari Oakes/MDedge News

Intensive outpatient programs (IOPs) frequently address these conditions within a biopsychosocial format, but it’s not common for IOPs to have this dual focus on chronic pain and substance use disorder (SUD), said Michael Stockin, MD, speaking in an interview at the scientific meeting of the American Pain Society.

Dr. Stockin said he and his collaborators recognized that, especially among a military population, the two conditions have considerable overlap, so it made sense to integrate behavioral treatment for both conditions in an intensive outpatient program. “Our hypothesis was that if you can use an intensive outpatient program to address substance use disorder, maybe you can actually add a chronic pain curriculum – like a functional restoration program to it.

“As a result of our study, we did find that there were significant differences in worst pain scores as a result of the program. In the people who took both the substance use disorder and chronic pain curriculum, we found significant reductions in total impairment, worst pain, and they also had less … substance use as well,” said Dr. Stockin.

In a quality improvement project, Dr. Stockin and collaborators compared short-term outcomes for patients who received IOP treatment addressing both chronic pain and SUD with those receiving SUD-only IOP.

For those participating in the joint IOP, scores indicating worst pain on the 0-10 numeric rating scale were reduced significantly, from 7.55 to 6.23 (P = .013). Scores on a functional measure of impairment, the Pain Outcomes Questionnaire Short Form (POQ-SF) also dropped significantly, from 84.92 to 63.50 (P = .034). The vitality domain of the POQ-SF also showed that patients had less impairment after participation in the joint IOP, with scores in that domain dropping from 20.17 to 17.25 (P = .024).

Looking at the total cohort, patient scores on the Brief Addiction Monitor (BAM) dropped significantly from baseline to the end of the intervention, indicating reduced substance use (P = .041). Mean scores for participants in the joint IOP were higher at baseline than for those in the SUD-only IOP (1.000 vs. 0.565). However, those participating in the joint IOP had lower mean postintervention BAM scores than the SUD-only cohort (0.071 vs. 0.174).

American veterans experience more severe pain and have a higher prevalence of chronic pain than nonveterans. Similarly, substance use disorders, and opioid use disorders in particular, present an urgent challenge to the military health system as part of reducing mortality from substance use, wrote Dr. Stockin, a chronic pain fellow in pain management at Walter Reed National Military Medical Center, Bethesda, Md., and colleagues in the poster presentation.

The project enrolled a total of 66 patients (10 female and 56 male). Of these, 18 participated in the joint SUD–chronic pain program, and 48 received usual treatment of the SUD-only IOP treatment. The mean overall age was 33.2 years, and 71.2% of participants were white.

Overall, 51 patients (77.3%) of participants had alcohol use disorder. Participants included active duty service members, veterans, and their dependents. Opioid and cannabis use disorders were experienced by a total of eight patients, and seven more patients had diagnoses of alcohol use disorder along with other substance use disorders.

All patients completed the BAM and received urine toxicology and alcohol breath testing at enrollment; drug and alcohol screening was completed at other points during the IOP treatment for both groups as well.

The joint IOP ran 3 full days a week, with a substance use curriculum in the morning and a pain management program in the afternoon; the SUD-only participants had three morning sessions weekly. Both interventions lasted 6 weeks, and Dr. Stockin said he and his colleagues would like to acquire longitudinal data to assess the durability of gains seen from the joint IOP.

The multidisciplinary team running the joint IOP was made up of an addiction/pain medicine physician, a clinical health psychologist, a physical therapist, social workers, and a nurse.

“This project is the first of its kind to find a significant reduction in pain burden while concurrently treating addiction and pain in an outpatient military health care setting,” Dr. Stockin and colleagues wrote in the poster accompanying the presentation.

“We had outcomes in both substance use and chronic pain that were positive, so it suggests that in the military health system, people may actually benefit from treating both chronic pain and substance use disorder concurrently. If you could harmonize those programs, you might be able to get good outcomes for soldiers and their families,” Dr. Stockin said.

Dr. Stockin reported no conflicts of interest. The project was funded by the Defense Health Agency.

[email protected]

MILWAUKEE – An interdisciplinary intensive outpatient treatment program addressing chronic pain and substance use disorder effectively addressed both diagnoses in a military population.

Kari Oakes/MDedge News

Intensive outpatient programs (IOPs) frequently address these conditions within a biopsychosocial format, but it’s not common for IOPs to have this dual focus on chronic pain and substance use disorder (SUD), said Michael Stockin, MD, speaking in an interview at the scientific meeting of the American Pain Society.

Dr. Stockin said he and his collaborators recognized that, especially among a military population, the two conditions have considerable overlap, so it made sense to integrate behavioral treatment for both conditions in an intensive outpatient program. “Our hypothesis was that if you can use an intensive outpatient program to address substance use disorder, maybe you can actually add a chronic pain curriculum – like a functional restoration program to it.

“As a result of our study, we did find that there were significant differences in worst pain scores as a result of the program. In the people who took both the substance use disorder and chronic pain curriculum, we found significant reductions in total impairment, worst pain, and they also had less … substance use as well,” said Dr. Stockin.

In a quality improvement project, Dr. Stockin and collaborators compared short-term outcomes for patients who received IOP treatment addressing both chronic pain and SUD with those receiving SUD-only IOP.

For those participating in the joint IOP, scores indicating worst pain on the 0-10 numeric rating scale were reduced significantly, from 7.55 to 6.23 (P = .013). Scores on a functional measure of impairment, the Pain Outcomes Questionnaire Short Form (POQ-SF) also dropped significantly, from 84.92 to 63.50 (P = .034). The vitality domain of the POQ-SF also showed that patients had less impairment after participation in the joint IOP, with scores in that domain dropping from 20.17 to 17.25 (P = .024).

Looking at the total cohort, patient scores on the Brief Addiction Monitor (BAM) dropped significantly from baseline to the end of the intervention, indicating reduced substance use (P = .041). Mean scores for participants in the joint IOP were higher at baseline than for those in the SUD-only IOP (1.000 vs. 0.565). However, those participating in the joint IOP had lower mean postintervention BAM scores than the SUD-only cohort (0.071 vs. 0.174).

American veterans experience more severe pain and have a higher prevalence of chronic pain than nonveterans. Similarly, substance use disorders, and opioid use disorders in particular, present an urgent challenge to the military health system as part of reducing mortality from substance use, wrote Dr. Stockin, a chronic pain fellow in pain management at Walter Reed National Military Medical Center, Bethesda, Md., and colleagues in the poster presentation.

The project enrolled a total of 66 patients (10 female and 56 male). Of these, 18 participated in the joint SUD–chronic pain program, and 48 received usual treatment of the SUD-only IOP treatment. The mean overall age was 33.2 years, and 71.2% of participants were white.

Overall, 51 patients (77.3%) of participants had alcohol use disorder. Participants included active duty service members, veterans, and their dependents. Opioid and cannabis use disorders were experienced by a total of eight patients, and seven more patients had diagnoses of alcohol use disorder along with other substance use disorders.

All patients completed the BAM and received urine toxicology and alcohol breath testing at enrollment; drug and alcohol screening was completed at other points during the IOP treatment for both groups as well.

The joint IOP ran 3 full days a week, with a substance use curriculum in the morning and a pain management program in the afternoon; the SUD-only participants had three morning sessions weekly. Both interventions lasted 6 weeks, and Dr. Stockin said he and his colleagues would like to acquire longitudinal data to assess the durability of gains seen from the joint IOP.

The multidisciplinary team running the joint IOP was made up of an addiction/pain medicine physician, a clinical health psychologist, a physical therapist, social workers, and a nurse.

“This project is the first of its kind to find a significant reduction in pain burden while concurrently treating addiction and pain in an outpatient military health care setting,” Dr. Stockin and colleagues wrote in the poster accompanying the presentation.

“We had outcomes in both substance use and chronic pain that were positive, so it suggests that in the military health system, people may actually benefit from treating both chronic pain and substance use disorder concurrently. If you could harmonize those programs, you might be able to get good outcomes for soldiers and their families,” Dr. Stockin said.

Dr. Stockin reported no conflicts of interest. The project was funded by the Defense Health Agency.

[email protected]

MILWAUKEE – An interdisciplinary intensive outpatient treatment program addressing chronic pain and substance use disorder effectively addressed both diagnoses in a military population.

Kari Oakes/MDedge News

Intensive outpatient programs (IOPs) frequently address these conditions within a biopsychosocial format, but it’s not common for IOPs to have this dual focus on chronic pain and substance use disorder (SUD), said Michael Stockin, MD, speaking in an interview at the scientific meeting of the American Pain Society.

Dr. Stockin said he and his collaborators recognized that, especially among a military population, the two conditions have considerable overlap, so it made sense to integrate behavioral treatment for both conditions in an intensive outpatient program. “Our hypothesis was that if you can use an intensive outpatient program to address substance use disorder, maybe you can actually add a chronic pain curriculum – like a functional restoration program to it.

“As a result of our study, we did find that there were significant differences in worst pain scores as a result of the program. In the people who took both the substance use disorder and chronic pain curriculum, we found significant reductions in total impairment, worst pain, and they also had less … substance use as well,” said Dr. Stockin.

In a quality improvement project, Dr. Stockin and collaborators compared short-term outcomes for patients who received IOP treatment addressing both chronic pain and SUD with those receiving SUD-only IOP.

For those participating in the joint IOP, scores indicating worst pain on the 0-10 numeric rating scale were reduced significantly, from 7.55 to 6.23 (P = .013). Scores on a functional measure of impairment, the Pain Outcomes Questionnaire Short Form (POQ-SF) also dropped significantly, from 84.92 to 63.50 (P = .034). The vitality domain of the POQ-SF also showed that patients had less impairment after participation in the joint IOP, with scores in that domain dropping from 20.17 to 17.25 (P = .024).

Looking at the total cohort, patient scores on the Brief Addiction Monitor (BAM) dropped significantly from baseline to the end of the intervention, indicating reduced substance use (P = .041). Mean scores for participants in the joint IOP were higher at baseline than for those in the SUD-only IOP (1.000 vs. 0.565). However, those participating in the joint IOP had lower mean postintervention BAM scores than the SUD-only cohort (0.071 vs. 0.174).

American veterans experience more severe pain and have a higher prevalence of chronic pain than nonveterans. Similarly, substance use disorders, and opioid use disorders in particular, present an urgent challenge to the military health system as part of reducing mortality from substance use, wrote Dr. Stockin, a chronic pain fellow in pain management at Walter Reed National Military Medical Center, Bethesda, Md., and colleagues in the poster presentation.

The project enrolled a total of 66 patients (10 female and 56 male). Of these, 18 participated in the joint SUD–chronic pain program, and 48 received usual treatment of the SUD-only IOP treatment. The mean overall age was 33.2 years, and 71.2% of participants were white.

Overall, 51 patients (77.3%) of participants had alcohol use disorder. Participants included active duty service members, veterans, and their dependents. Opioid and cannabis use disorders were experienced by a total of eight patients, and seven more patients had diagnoses of alcohol use disorder along with other substance use disorders.

All patients completed the BAM and received urine toxicology and alcohol breath testing at enrollment; drug and alcohol screening was completed at other points during the IOP treatment for both groups as well.

The joint IOP ran 3 full days a week, with a substance use curriculum in the morning and a pain management program in the afternoon; the SUD-only participants had three morning sessions weekly. Both interventions lasted 6 weeks, and Dr. Stockin said he and his colleagues would like to acquire longitudinal data to assess the durability of gains seen from the joint IOP.

The multidisciplinary team running the joint IOP was made up of an addiction/pain medicine physician, a clinical health psychologist, a physical therapist, social workers, and a nurse.

“This project is the first of its kind to find a significant reduction in pain burden while concurrently treating addiction and pain in an outpatient military health care setting,” Dr. Stockin and colleagues wrote in the poster accompanying the presentation.

“We had outcomes in both substance use and chronic pain that were positive, so it suggests that in the military health system, people may actually benefit from treating both chronic pain and substance use disorder concurrently. If you could harmonize those programs, you might be able to get good outcomes for soldiers and their families,” Dr. Stockin said.

Dr. Stockin reported no conflicts of interest. The project was funded by the Defense Health Agency.

[email protected]

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

For women with symptomatic uterine leiomyomas and abnormal uterine bleeding, ulipristal acetate treatment significantly improved quality of life over placebo, according to a study of the intention-to-treat populations of the randomized, double-blind, phase III VENUS I and VENUS II trials.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

In these pivotal studies, ulipristal (Ella) at either 5 mg or 10 mg significantly improved both rate of and time to amenorrhea, noted Andrea S. Lukes, MD, of Carolina Women’s Research and Wellness Center in Durham, N.C. To assess effects on quality of life, she and her associates analyzed baseline and 12-week responses to the widely validated Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QOL) questionnaire, which examined factors such as symptom severity, energy and mood, physical and social activities, self-consciousness, and sexual functioning.

Among 589 patients in the analysis, 169 received placebo, 215 received 5 mg ulipristal, and 205 received 10 mg ulipristal. At baseline, average total quality of life scores on UFS-QOL were 33 (standard deviation, 220), 32 (SD, 21), and 36 (SD, 23), respectively, the researchers wrote in Obstetrics & Gynecology.

After 12 weeks of treatment, both doses of ulipristal were associated with significantly greater improvements on all UFS-QOL scales, compared with placebo (P less than .001). For example, on a scale of 0-100, symptom severity improved by a mean of 23 with ulipristal 5 mg and by a mean of 30 with ulipristal 10 mg (both P less than .001 versus placebo).

“Although a small proportion of patients experienced no change or some worsening in these outcomes, the majority of women reported clear improvements; for example, more than 70% of patients in the ulipristal treatment arms achieved a meaningful improvement of 30 or more points on the Revised Activities subscale,” the researchers wrote.

Additionally, significantly greater improvements in physical and social activities were seen for both ulipristal doses, compared with placebo, from baseline to the end of treatment.

The VENUS II trial included two 12-week treatment courses. In this trial, women who switched from ulipristal to placebo experienced some worsening in quality of life, while those who switched from placebo to ulipristal improved their UFS-QOL scores, the investigators said. Patients who stayed on ulipristal throughout continued to benefit from one treatment course to the next.

The researchers concluded that the findings, “taken together with the significant improvements in amenorrhea, suggest that ulipristal is a promising, noninvasive treatment option for women suffering from symptomatic uterine leiomyomas.”

Allergan provided funding. Dr. Lukes disclosed ties to Allergan, AbbVie, Myovant, Merck, and several other companies. Four of the coauthors are employees of Allergan, and the two remaining coauthors had links to a number of pharmaceutical companies.

SOURCE: Lukes AS et al. Obstet Gynecol 2019;133 (5):869-78.

For women with symptomatic uterine leiomyomas and abnormal uterine bleeding, ulipristal acetate treatment significantly improved quality of life over placebo, according to a study of the intention-to-treat populations of the randomized, double-blind, phase III VENUS I and VENUS II trials.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

In these pivotal studies, ulipristal (Ella) at either 5 mg or 10 mg significantly improved both rate of and time to amenorrhea, noted Andrea S. Lukes, MD, of Carolina Women’s Research and Wellness Center in Durham, N.C. To assess effects on quality of life, she and her associates analyzed baseline and 12-week responses to the widely validated Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QOL) questionnaire, which examined factors such as symptom severity, energy and mood, physical and social activities, self-consciousness, and sexual functioning.

Among 589 patients in the analysis, 169 received placebo, 215 received 5 mg ulipristal, and 205 received 10 mg ulipristal. At baseline, average total quality of life scores on UFS-QOL were 33 (standard deviation, 220), 32 (SD, 21), and 36 (SD, 23), respectively, the researchers wrote in Obstetrics & Gynecology.

After 12 weeks of treatment, both doses of ulipristal were associated with significantly greater improvements on all UFS-QOL scales, compared with placebo (P less than .001). For example, on a scale of 0-100, symptom severity improved by a mean of 23 with ulipristal 5 mg and by a mean of 30 with ulipristal 10 mg (both P less than .001 versus placebo).

“Although a small proportion of patients experienced no change or some worsening in these outcomes, the majority of women reported clear improvements; for example, more than 70% of patients in the ulipristal treatment arms achieved a meaningful improvement of 30 or more points on the Revised Activities subscale,” the researchers wrote.

Additionally, significantly greater improvements in physical and social activities were seen for both ulipristal doses, compared with placebo, from baseline to the end of treatment.

The VENUS II trial included two 12-week treatment courses. In this trial, women who switched from ulipristal to placebo experienced some worsening in quality of life, while those who switched from placebo to ulipristal improved their UFS-QOL scores, the investigators said. Patients who stayed on ulipristal throughout continued to benefit from one treatment course to the next.

The researchers concluded that the findings, “taken together with the significant improvements in amenorrhea, suggest that ulipristal is a promising, noninvasive treatment option for women suffering from symptomatic uterine leiomyomas.”

Allergan provided funding. Dr. Lukes disclosed ties to Allergan, AbbVie, Myovant, Merck, and several other companies. Four of the coauthors are employees of Allergan, and the two remaining coauthors had links to a number of pharmaceutical companies.

SOURCE: Lukes AS et al. Obstet Gynecol 2019;133 (5):869-78.

For women with symptomatic uterine leiomyomas and abnormal uterine bleeding, ulipristal acetate treatment significantly improved quality of life over placebo, according to a study of the intention-to-treat populations of the randomized, double-blind, phase III VENUS I and VENUS II trials.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

In these pivotal studies, ulipristal (Ella) at either 5 mg or 10 mg significantly improved both rate of and time to amenorrhea, noted Andrea S. Lukes, MD, of Carolina Women’s Research and Wellness Center in Durham, N.C. To assess effects on quality of life, she and her associates analyzed baseline and 12-week responses to the widely validated Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QOL) questionnaire, which examined factors such as symptom severity, energy and mood, physical and social activities, self-consciousness, and sexual functioning.

Among 589 patients in the analysis, 169 received placebo, 215 received 5 mg ulipristal, and 205 received 10 mg ulipristal. At baseline, average total quality of life scores on UFS-QOL were 33 (standard deviation, 220), 32 (SD, 21), and 36 (SD, 23), respectively, the researchers wrote in Obstetrics & Gynecology.

After 12 weeks of treatment, both doses of ulipristal were associated with significantly greater improvements on all UFS-QOL scales, compared with placebo (P less than .001). For example, on a scale of 0-100, symptom severity improved by a mean of 23 with ulipristal 5 mg and by a mean of 30 with ulipristal 10 mg (both P less than .001 versus placebo).

“Although a small proportion of patients experienced no change or some worsening in these outcomes, the majority of women reported clear improvements; for example, more than 70% of patients in the ulipristal treatment arms achieved a meaningful improvement of 30 or more points on the Revised Activities subscale,” the researchers wrote.

Additionally, significantly greater improvements in physical and social activities were seen for both ulipristal doses, compared with placebo, from baseline to the end of treatment.

The VENUS II trial included two 12-week treatment courses. In this trial, women who switched from ulipristal to placebo experienced some worsening in quality of life, while those who switched from placebo to ulipristal improved their UFS-QOL scores, the investigators said. Patients who stayed on ulipristal throughout continued to benefit from one treatment course to the next.

The researchers concluded that the findings, “taken together with the significant improvements in amenorrhea, suggest that ulipristal is a promising, noninvasive treatment option for women suffering from symptomatic uterine leiomyomas.”

Allergan provided funding. Dr. Lukes disclosed ties to Allergan, AbbVie, Myovant, Merck, and several other companies. Four of the coauthors are employees of Allergan, and the two remaining coauthors had links to a number of pharmaceutical companies.

SOURCE: Lukes AS et al. Obstet Gynecol 2019;133 (5):869-78.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

External cephalic version in breech pregnancies is more likely to succeed in multiparous women with a lower body mass index (BMI) who have a larger forebag, according to results of a single-center retrospective study.

Writing in Obstetrics & Gynecology, Ofer Isakov, MD, PhD, and colleagues from the Sourasky Medical Center, Tel Aviv, reported the results of a study of 250 women with singleton pregnancies and breech presentation who underwent external cephalic version (ECV) to turn the baby at 36-41 weeks’ gestation.

The overall success rate of the procedure was 65%. However, women with no forebag – the pocket of amniotic fluid in front of the fetal presenting part – had a 3%-10% chance of successful version, while those with a forebag size greater than 1 cm had a 96%-97% probability of success.

Women with a BMI greater than 29 had a very low chance of success, which the authors suggested was likely attributable to a thicker abdominal wall that made manipulation more difficult. However, among women with a BMI of 29 or below, success was significantly associated with forebag size.

Among women with a forebag of 1 cm in size, multiparous women had a significantly higher chance of success than nulliparous women (81%-91% vs. 0%-24%, respectively).

Dr. Isakov and colleagues suggested that the impact of multiparity could relate to late engagement or the relative laxity of the abdomen in women who had experienced previous births.

The authors then developed a decision tree predictive model of success for ECV, which had a prediction accuracy of 92%.

“External version is a simple and effective procedure that can reduce the cesarean delivery rate, but counseling patients on the risks and success rates of version is challenging owing to the lack of validated models to predict success,” Dr. Isakov and colleagues wrote. “The ability to predict the outcome of an ECV attempt may improve the rates of patient consent and prevent the performance of many unpleasant procedures with low chance for success.”

They noted that their success rate was higher than that seen in other studies of ECV and suggested this may be because all the procedures were performed by a single experienced practitioner, and the mean BMI of the cohort was lower than that in earlier studies.

None of the authors declared any relevant financial disclosures, and there was no external funding.

SOURCE: Isakov O et al. Obstet Gynecol. 2019;133:869-78.

External cephalic version in breech pregnancies is more likely to succeed in multiparous women with a lower body mass index (BMI) who have a larger forebag, according to results of a single-center retrospective study.

Writing in Obstetrics & Gynecology, Ofer Isakov, MD, PhD, and colleagues from the Sourasky Medical Center, Tel Aviv, reported the results of a study of 250 women with singleton pregnancies and breech presentation who underwent external cephalic version (ECV) to turn the baby at 36-41 weeks’ gestation.

The overall success rate of the procedure was 65%. However, women with no forebag – the pocket of amniotic fluid in front of the fetal presenting part – had a 3%-10% chance of successful version, while those with a forebag size greater than 1 cm had a 96%-97% probability of success.

Women with a BMI greater than 29 had a very low chance of success, which the authors suggested was likely attributable to a thicker abdominal wall that made manipulation more difficult. However, among women with a BMI of 29 or below, success was significantly associated with forebag size.

Among women with a forebag of 1 cm in size, multiparous women had a significantly higher chance of success than nulliparous women (81%-91% vs. 0%-24%, respectively).

Dr. Isakov and colleagues suggested that the impact of multiparity could relate to late engagement or the relative laxity of the abdomen in women who had experienced previous births.

The authors then developed a decision tree predictive model of success for ECV, which had a prediction accuracy of 92%.

“External version is a simple and effective procedure that can reduce the cesarean delivery rate, but counseling patients on the risks and success rates of version is challenging owing to the lack of validated models to predict success,” Dr. Isakov and colleagues wrote. “The ability to predict the outcome of an ECV attempt may improve the rates of patient consent and prevent the performance of many unpleasant procedures with low chance for success.”

They noted that their success rate was higher than that seen in other studies of ECV and suggested this may be because all the procedures were performed by a single experienced practitioner, and the mean BMI of the cohort was lower than that in earlier studies.

None of the authors declared any relevant financial disclosures, and there was no external funding.

SOURCE: Isakov O et al. Obstet Gynecol. 2019;133:869-78.

External cephalic version in breech pregnancies is more likely to succeed in multiparous women with a lower body mass index (BMI) who have a larger forebag, according to results of a single-center retrospective study.

Writing in Obstetrics & Gynecology, Ofer Isakov, MD, PhD, and colleagues from the Sourasky Medical Center, Tel Aviv, reported the results of a study of 250 women with singleton pregnancies and breech presentation who underwent external cephalic version (ECV) to turn the baby at 36-41 weeks’ gestation.

The overall success rate of the procedure was 65%. However, women with no forebag – the pocket of amniotic fluid in front of the fetal presenting part – had a 3%-10% chance of successful version, while those with a forebag size greater than 1 cm had a 96%-97% probability of success.

Women with a BMI greater than 29 had a very low chance of success, which the authors suggested was likely attributable to a thicker abdominal wall that made manipulation more difficult. However, among women with a BMI of 29 or below, success was significantly associated with forebag size.

Among women with a forebag of 1 cm in size, multiparous women had a significantly higher chance of success than nulliparous women (81%-91% vs. 0%-24%, respectively).

Dr. Isakov and colleagues suggested that the impact of multiparity could relate to late engagement or the relative laxity of the abdomen in women who had experienced previous births.

The authors then developed a decision tree predictive model of success for ECV, which had a prediction accuracy of 92%.

“External version is a simple and effective procedure that can reduce the cesarean delivery rate, but counseling patients on the risks and success rates of version is challenging owing to the lack of validated models to predict success,” Dr. Isakov and colleagues wrote. “The ability to predict the outcome of an ECV attempt may improve the rates of patient consent and prevent the performance of many unpleasant procedures with low chance for success.”

They noted that their success rate was higher than that seen in other studies of ECV and suggested this may be because all the procedures were performed by a single experienced practitioner, and the mean BMI of the cohort was lower than that in earlier studies.

None of the authors declared any relevant financial disclosures, and there was no external funding.

SOURCE: Isakov O et al. Obstet Gynecol. 2019;133:869-78.

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.

Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.

After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.

Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.

The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.

There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.

The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.

An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.

SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.

Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.

After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.

Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.

The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.

There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.

The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.

An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.

SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.

Patients whose rheumatoid arthritis was in sustained remission had similar rates of flare for the first 9 months after they tapered off either their conventional synthetic disease-modifying antirheumatic drug (DMARD), or their tumor necrosis factor (TNF) inhibitor, researchers reported.

After the first year, first author Elise van Mulligen of Erasmus University Medical Center in Rotterdam, the Netherlands, and her associates found that flares rates were 10% lower among patients who first tapered conventional synthetic DMARDs, a difference that was not statistically significant. Because secondary endpoints also were similar between groups, patients should consider first tapering off their TNF inhibitor to save costs and reduce side effects, the researchers wrote in Annals of the Rheumatic Diseases.

Over the past decade, better drugs, treat-to-target approaches, and earlier disease detection have vastly improved outcomes in rheumatoid arthritis. As more patients achieve sustained remission, they are tapering off therapy in accordance with current guidelines. This multicenter, single-blinded, randomized trial (Tapering Strategies in Rheumatoid Arthritis [TARA]) is one of the first to compare tapering strategies, rather than looking at only whether tapering is feasible.

The study included 189 patients from the Netherlands whose rheumatoid arthritis was in sustained remission (Disease Activity Score [DAS] less than 2.4 and swollen joint count less than 1 for at least 3 months) on a conventional synthetic DMARD plus a TNF inhibitor. Patients were randomly assigned to either halve the conventional synthetic DMARD dose, or to double the TNF-inhibitor dosing interval. After 3 months, they cut the dose of their assigned taper medication to 25% of baseline. If they stayed in remission, they stopped the medication 3 months later. They avoided glucocorticoids throughout.

There were no serious adverse events related to tapering. Cumulative rates of flare at 1 year (DAS greater than 2.4 or swollen joint count greater than 1) were 33% for conventional synthetic DMARD taper (95% confidence interval, 24%-43%) and 43% (95% CI, 33%-53%) for TNF-inhibitor taper (P = .17). The two groups also had similar scores at 1 year on the DAS, Health Assessment Questionnaire-Disability Index, and European Quality of Life-5 Dimensions index.

The suggestion to first taper off TNF inhibitors reflects current European League Against Rheumatism guidelines, which advise first tapering glucocorticoids, then biologic DMARDS, and finally conventional synthetic DMARDs. “Our results and the fact that TNF blockers are more expensive than conventional synthetic DMARDs support the aforementioned tapering order,” the researchers concluded.

An unrestricted grant from ZonMW supported the work. The investigators reported having no conflicts of interest.

SOURCE: Mulligen E et al. Ann Rheum Dis. 2019 Apr 6. doi: 10.1136/annrheumdis-2018-214970.