Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

[email protected]

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

[email protected]

Louisiana physicians who treat Medicaid patients for hepatitis C will see less administrative burden under an arrangement approved by the Centers for Medicare & Medicaid Services.

Dynamic Graphics/Thinkstockphotos

Beginning July 15, physicians will no longer have to seek prior authorization or preauthorization to prescribe the authorized generic version of Epclusa (sofosbuvir/velpatasvir) to any Medicaid patient with hepatitis C. There will be no forms to file.

The change comes as part of a supplemental rebate agreement approved June 26 by CMS. That same day, Louisiana announced a deal with Asegua Therapeutics, a wholly owned subsidiary of Epclusa maker Gilead, that essentially caps the annual cost to the state for treating hepatitis C in incarcerated patients and Medicaid recipients.

State officials estimate about 39,000 Louisianans fit those criteria; the goal of the program is to cure at least 31,000 of them by the time the 5-year agreement expires.

“This new model has the potential to save many lives and improve the health of our citizens,” Louisiana Gov. John Bel Edwards (D) said in a statement. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this 5-year partnership. Ultimately our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

The agreement was designed to change very little in terms of the mechanics of how Medicaid managed care organizations, which cover most of the state’s Medicaid population and handle coverage and claims. The biggest change is that, when a spending cap is reached, Asegua will rebate 100% excess costs to the state. Louisiana officials did not disclose what the annual financial caps were as part of the agreement.

“We really thought it was important to leave the system – as much as possible – intact because we think that is going to make us most successful,” Alex Billioux, MD, of the Louisiana Department of Health said in an interview. “We think it leverages existing patient relationships and existing [Medicaid managed care organization] care management responsibilities.”

He added that, by keeping current processes unchanged, “it takes what is an otherwise very complicated arrangement with the state and makes it a little simpler.”

Patients will see no change in terms of copayments for the approved generic topping out at $3 depending on income level as they would have prior to the agreement. The biggest difference for them is that “people who couldn’t be treated are now going to have access to those prescriptions,” Dr. Billioux said.

Some cautious optimism surrounds this kind of arrangement and the potential effect it can have on the affected population.

“Innovation geared to improve access to hepatitis C treatment is critical, particularly in areas like Louisiana where treatment rates for Medicaid patients have been very low,” Robert Brown, MD, member of the American Liver Foundation’s National Medical Advisory Committee and hepatologist at Weill Cornell Medical College, New York, said. “If we can enhance patient access to treatment, we know we will improve health outcomes. However, it is too early to tell if this innovation will be a success. At the end of the day, the number of additional patients cured will determine if this was the right approach.”

[email protected]

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

[email protected]

SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

[email protected]

SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

[email protected]

SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

MILAN – Health-related quality of life improved for patients with moderate to severe genital psoriasis while they received ixekizumab, according to data presented at the World Congress of Dermatology.

After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.

Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.

In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.

Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.

In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.

Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.

Participants also completed the DLQI, which was administered nine times over the 52-week study period.

From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.

The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.

Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..

“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.

Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.

[email protected]

MILAN – Health-related quality of life improved for patients with moderate to severe genital psoriasis while they received ixekizumab, according to data presented at the World Congress of Dermatology.

After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.

Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.

In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.

Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.

In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.

Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.

Participants also completed the DLQI, which was administered nine times over the 52-week study period.

From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.

The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.

Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..

“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.

Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.

[email protected]

MILAN – Health-related quality of life improved for patients with moderate to severe genital psoriasis while they received ixekizumab, according to data presented at the World Congress of Dermatology.

After 12 weeks of ixekizumab administration, nearly half of patients who received ixekizumab in the randomized, double-blind, placebo-controlled trial achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, compared with fewer than 5% of those receiving placebo. At the end of one year, 46.7% of the original ixekizumab group and 50.8% of those who transitioned to ixekizumab from placebo via an open-label extension arm achieved a DLQI of 0 or 1. A DLQI score of 0 or 1 on a 30-point scale indicated that psoriasis had no effect on health-related quality of life.

Among patients with plaque psoriasis, genital involvement is common – present in over 60% at some point during the disease course, Lyn Guenther, MD, of Guenther Dermatology Research Centre, London, Ont., and her colleagues wrote in the poster accompanying the presentation. Sexual health and overall quality of life can be negatively affected by genital psoriasis, they added.

In the study, adult patients were included if they had chronic plaque psoriasis present in genital and nongenital areas. For overall psoriasis and genital involvement, the Static Physician’s Global Assessment (sPGA) was 3 or greater, and total body surface area involvement was at least 1%. Also, patients had to have failed or been intolerant to at least one topical therapy for genital psoriasis.

Patients were excluded if they had genital pustules or vesicles, significant uncontrolled medical or psychiatric comorbidities, recent infection, or prior interleukin-17 antagonist treatment.

In all, patients received ixekizumab 160 mg (75 patients) or placebo (74) subcutaneously every 2 weeks during the initial 12-week study period. For the open-label extension arm, 74 patients in the active arm and 65 patients in the placebo arm went on to receive 80 mg of ixekizumab every 4 weeks, with a step-up option to every other week dosing depending on clinical response.

Patients were given the Short Form Health Survey (SF-36) at baseline and at week 12 and week 52; investigators recorded the mean change for baseline for both the physical and mental component.

Participants also completed the DLQI, which was administered nine times over the 52-week study period.

From baseline, SF-36 scores climbed in both the physical and mental domains for those on ixekizumab, wrote Dr. Guenther and her coinvestigators, with “improvements in all SF-36 domains” for those on ixekizumab at 12 weeks, which continued through week 52. For patients who transitioned to ixekizumab from placebo, “improvements in all SF-36 domains were achieved at week 52,” they wrote.

The mean change from baseline on the SF-36 for the ixekizumab population was 3.5 on the physical domain and 4.8 on the mental component. For the placebo-ixekizumab group, scores improved by a mean 4.5 on the physical domain and 4.9 on the mental domain. Those who stayed on ixekizumab saw some decline in SF-36 scores, with a physical component improvement of 2.5 and mental component improvement of 3.6 at 52 weeks.

Ixekizumab (Taltz), a monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis, and active psoriatic arthritis..

“Ixekizumab provided clinically meaningful and persistent improvements in HRQoL in patients with moderate to severe genital psoriasis,” wrote Dr. Guenther and her colleagues.

Dr. Guenther and two coauthors reported receiving remuneration from several pharmaceutical companies, including Eli Lilly, which funded the study. Four coauthors are employees and shareholders of Eli Lilly.

[email protected]

The tyrosine kinase inhibitor dasatinib was found to transiently inhibit CAR T-cell function in mice, suggesting applicability as an on-off control for CAR T-cell therapy, investigators report.

“In this study, we focused our efforts on evaluating dasatinib as a control drug for CAR T cells,” wrote Katrin Mestermann, PhD, of the University of Würzburg in Germany and colleagues in Science Translational Medicine.

The researchers explored the pharmacological effects of dasatinib on CAR T-cell function using a mouse xenograft model. In this model, dasatinib was administered every 6 hours to sustain serum levels above a mandatory threshold to ensure human pharmacokinetic equivalence.

The team observed that dasatinib interferes with several cellular mechanisms that effect CAR T-cell activity, including inhibition of protein phosphorylation and cytokine secretion, among others.

Short-term administration of dasatinib was shown to not alter antilymphoma activity of CD19-CAR T cells, according to data from in vivo experiments.

In addition, upon cessation of dasatinib, CAR T-cell antitumor activity was rapidly restored, based on in vitro experiment data.

Dr. Mestermann and her colleagues also noted that the dose of dasatinib was titratable to attain either partial or complete inhibition of CAR T-cell activity. These effects could be maintained for several days without altering T-cell survival.

“A short treatment course of dasatinib, administered early after CAR T-cell infusion, protects a proportion of mice from otherwise fatal cytokine release syndrome,” the researchers wrote.

Cytokine release syndrome is the most frequently seen acute toxicity linked to CAR T-cell therapy, they explained.

“Further studies are warranted to determine whether dasatinib is also effective in clinical situations with established cytokine release syndrome,” they concluded.

The study was funded by the Cluster Biotechnologie Bayern and Free State of Bavaria, the German Cancer Aid, and the University of Würzburg. The authors reported financial affiliations with Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Takeda, and others.

SOURCE: Mestermann K et al. Sci Transl Med. 2019 Jul 3. doi: 10.1126/scitranslmed.aau5907.

The tyrosine kinase inhibitor dasatinib was found to transiently inhibit CAR T-cell function in mice, suggesting applicability as an on-off control for CAR T-cell therapy, investigators report.

“In this study, we focused our efforts on evaluating dasatinib as a control drug for CAR T cells,” wrote Katrin Mestermann, PhD, of the University of Würzburg in Germany and colleagues in Science Translational Medicine.

The researchers explored the pharmacological effects of dasatinib on CAR T-cell function using a mouse xenograft model. In this model, dasatinib was administered every 6 hours to sustain serum levels above a mandatory threshold to ensure human pharmacokinetic equivalence.

The team observed that dasatinib interferes with several cellular mechanisms that effect CAR T-cell activity, including inhibition of protein phosphorylation and cytokine secretion, among others.

Short-term administration of dasatinib was shown to not alter antilymphoma activity of CD19-CAR T cells, according to data from in vivo experiments.

In addition, upon cessation of dasatinib, CAR T-cell antitumor activity was rapidly restored, based on in vitro experiment data.

Dr. Mestermann and her colleagues also noted that the dose of dasatinib was titratable to attain either partial or complete inhibition of CAR T-cell activity. These effects could be maintained for several days without altering T-cell survival.

“A short treatment course of dasatinib, administered early after CAR T-cell infusion, protects a proportion of mice from otherwise fatal cytokine release syndrome,” the researchers wrote.

Cytokine release syndrome is the most frequently seen acute toxicity linked to CAR T-cell therapy, they explained.

“Further studies are warranted to determine whether dasatinib is also effective in clinical situations with established cytokine release syndrome,” they concluded.

The study was funded by the Cluster Biotechnologie Bayern and Free State of Bavaria, the German Cancer Aid, and the University of Würzburg. The authors reported financial affiliations with Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Takeda, and others.

SOURCE: Mestermann K et al. Sci Transl Med. 2019 Jul 3. doi: 10.1126/scitranslmed.aau5907.

The tyrosine kinase inhibitor dasatinib was found to transiently inhibit CAR T-cell function in mice, suggesting applicability as an on-off control for CAR T-cell therapy, investigators report.

“In this study, we focused our efforts on evaluating dasatinib as a control drug for CAR T cells,” wrote Katrin Mestermann, PhD, of the University of Würzburg in Germany and colleagues in Science Translational Medicine.

The researchers explored the pharmacological effects of dasatinib on CAR T-cell function using a mouse xenograft model. In this model, dasatinib was administered every 6 hours to sustain serum levels above a mandatory threshold to ensure human pharmacokinetic equivalence.

The team observed that dasatinib interferes with several cellular mechanisms that effect CAR T-cell activity, including inhibition of protein phosphorylation and cytokine secretion, among others.

Short-term administration of dasatinib was shown to not alter antilymphoma activity of CD19-CAR T cells, according to data from in vivo experiments.

In addition, upon cessation of dasatinib, CAR T-cell antitumor activity was rapidly restored, based on in vitro experiment data.

Dr. Mestermann and her colleagues also noted that the dose of dasatinib was titratable to attain either partial or complete inhibition of CAR T-cell activity. These effects could be maintained for several days without altering T-cell survival.

“A short treatment course of dasatinib, administered early after CAR T-cell infusion, protects a proportion of mice from otherwise fatal cytokine release syndrome,” the researchers wrote.

Cytokine release syndrome is the most frequently seen acute toxicity linked to CAR T-cell therapy, they explained.

“Further studies are warranted to determine whether dasatinib is also effective in clinical situations with established cytokine release syndrome,” they concluded.

The study was funded by the Cluster Biotechnologie Bayern and Free State of Bavaria, the German Cancer Aid, and the University of Würzburg. The authors reported financial affiliations with Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Takeda, and others.

SOURCE: Mestermann K et al. Sci Transl Med. 2019 Jul 3. doi: 10.1126/scitranslmed.aau5907.

AMSTERDAM – Rituximab maintenance therapy did not significantly prolong disease-free survival among patients with diffuse large B-cell lymphoma in complete remission after induction chemotherapy, investigators in the HOVON-Nordic trial collaboration found.

Among 380 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission following induction chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the median disease-free survival (DFS) after a median follow-up of 79.9 months had not been reached for patients randomized to either rituximab maintenance therapy or observation alone, reported Pieternella J. Lugtenburg, MD, PhD, from Erasmus Medical Center in Rotterdam, the Netherlands.

“In patients with diffuse large B-cell lymphoma in first complete remission after R-CHOP induction therapy, rituximab maintenance therapy does not prolong disease-free survival, and we could not identify a clinical subgroup that benefited,” she said at the annual congress of the European Hematology Association.

The randomized, phase 3 HOVON-Nordic LG trial compared R-CHOP-14 with rituximab delivered on day 1 for four cycles in one arm, and on days 1 and 8 in the comparison arm (R2-CHOP). Patients were assessed for response after four cycles, and those with progressive disease were taken off the study. The remaining patients continued on their assigned regimen for an additional four cycles and second assessment, and those who had complete responses then underwent a second randomization to rituximab maintenance or observation. Patients randomized to maintenance could receive up to 12 8-week cycles.

The second randomization was stratified by age (18-65 vs. 66-80 years), age-adjusted International Prognostic Index score, and R-CHOP regimen (one or two infusions per cycle in the first randomization).

The induction phase found no significant benefit for the additional rituximab infusion for the primary endpoint of progression-free survival, with 3-year PFS rates of 74% for R-CHOP and 71% for R2-CHOP. Respective 5-year PFS rates were 68% and 62%.

There were no differences between the arms by any of the stratification factors, and no difference in overall survival.

Dr. Lugtenburg presented results of the maintenance phase, which included all patients in complete remission at least 4 weeks after the last cycle of R-CHOP-14 who did not have rituximab-related adverse events or active infections.

A total of 195 patients were randomized to observation, and 185 to maintenance. Of this latter group, 149 patients received all 12 cycles, with a median duration of exposure of 22.5 months.

As noted, DFS, the primary endpoint for the maintenance phase, was not significantly different between the arms, with 136 events in the maintenance arm versus 134 in the observation arm. A total of 21 patients assigned to maintenance died, and 22 patients assigned to observation died during follow-up.

The respective 5-year DFS rates were 79% and 74%, a difference that was not statistically significant.

There were no significant differences between the arms in either time to relapse or death, and no difference in overall survival.

In the question-and-answer section following her talk, Marek Trnený, MD, from Charles University in Prague, pointed out that, in the NHL 13 study, which looked at rituximab maintenance for patients with DLBCL or follicular lymphoma in first remission, there was an apparent clinical benefit with rituximab maintenance for men with low International Prognostic Index scores, and asked whether Dr. Lugtenburg and colleagues had seen similar trends.

“We knew about this finding, and we really didn’t see any differences between males and females, not only in terms of efficacy, but also in terms of toxicity, they had actually the same rates of toxicity,” she said.

In NHL 13, women had a significantly higher incidence of grade 3-4 adverse events, compared with men.

The study was sponsored by HOVON, the HematoOncology Foundation for Adults in the Netherlands, with additional support from Roche. Dr. Lugtenburg reported consultancy for and research funding from Roche and others. Dr. Trnený reported advisory board activity, research support, and honoraria from Roche and others.

SOURCE: Lugtenburg PJ et al. EHA 2019, Abstract S1559.

AMSTERDAM – Rituximab maintenance therapy did not significantly prolong disease-free survival among patients with diffuse large B-cell lymphoma in complete remission after induction chemotherapy, investigators in the HOVON-Nordic trial collaboration found.

Among 380 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission following induction chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the median disease-free survival (DFS) after a median follow-up of 79.9 months had not been reached for patients randomized to either rituximab maintenance therapy or observation alone, reported Pieternella J. Lugtenburg, MD, PhD, from Erasmus Medical Center in Rotterdam, the Netherlands.

“In patients with diffuse large B-cell lymphoma in first complete remission after R-CHOP induction therapy, rituximab maintenance therapy does not prolong disease-free survival, and we could not identify a clinical subgroup that benefited,” she said at the annual congress of the European Hematology Association.

The randomized, phase 3 HOVON-Nordic LG trial compared R-CHOP-14 with rituximab delivered on day 1 for four cycles in one arm, and on days 1 and 8 in the comparison arm (R2-CHOP). Patients were assessed for response after four cycles, and those with progressive disease were taken off the study. The remaining patients continued on their assigned regimen for an additional four cycles and second assessment, and those who had complete responses then underwent a second randomization to rituximab maintenance or observation. Patients randomized to maintenance could receive up to 12 8-week cycles.

The second randomization was stratified by age (18-65 vs. 66-80 years), age-adjusted International Prognostic Index score, and R-CHOP regimen (one or two infusions per cycle in the first randomization).

The induction phase found no significant benefit for the additional rituximab infusion for the primary endpoint of progression-free survival, with 3-year PFS rates of 74% for R-CHOP and 71% for R2-CHOP. Respective 5-year PFS rates were 68% and 62%.

There were no differences between the arms by any of the stratification factors, and no difference in overall survival.

Dr. Lugtenburg presented results of the maintenance phase, which included all patients in complete remission at least 4 weeks after the last cycle of R-CHOP-14 who did not have rituximab-related adverse events or active infections.

A total of 195 patients were randomized to observation, and 185 to maintenance. Of this latter group, 149 patients received all 12 cycles, with a median duration of exposure of 22.5 months.

As noted, DFS, the primary endpoint for the maintenance phase, was not significantly different between the arms, with 136 events in the maintenance arm versus 134 in the observation arm. A total of 21 patients assigned to maintenance died, and 22 patients assigned to observation died during follow-up.

The respective 5-year DFS rates were 79% and 74%, a difference that was not statistically significant.

There were no significant differences between the arms in either time to relapse or death, and no difference in overall survival.

In the question-and-answer section following her talk, Marek Trnený, MD, from Charles University in Prague, pointed out that, in the NHL 13 study, which looked at rituximab maintenance for patients with DLBCL or follicular lymphoma in first remission, there was an apparent clinical benefit with rituximab maintenance for men with low International Prognostic Index scores, and asked whether Dr. Lugtenburg and colleagues had seen similar trends.

“We knew about this finding, and we really didn’t see any differences between males and females, not only in terms of efficacy, but also in terms of toxicity, they had actually the same rates of toxicity,” she said.

In NHL 13, women had a significantly higher incidence of grade 3-4 adverse events, compared with men.

The study was sponsored by HOVON, the HematoOncology Foundation for Adults in the Netherlands, with additional support from Roche. Dr. Lugtenburg reported consultancy for and research funding from Roche and others. Dr. Trnený reported advisory board activity, research support, and honoraria from Roche and others.

SOURCE: Lugtenburg PJ et al. EHA 2019, Abstract S1559.

AMSTERDAM – Rituximab maintenance therapy did not significantly prolong disease-free survival among patients with diffuse large B-cell lymphoma in complete remission after induction chemotherapy, investigators in the HOVON-Nordic trial collaboration found.

Among 380 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission following induction chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the median disease-free survival (DFS) after a median follow-up of 79.9 months had not been reached for patients randomized to either rituximab maintenance therapy or observation alone, reported Pieternella J. Lugtenburg, MD, PhD, from Erasmus Medical Center in Rotterdam, the Netherlands.

“In patients with diffuse large B-cell lymphoma in first complete remission after R-CHOP induction therapy, rituximab maintenance therapy does not prolong disease-free survival, and we could not identify a clinical subgroup that benefited,” she said at the annual congress of the European Hematology Association.

The randomized, phase 3 HOVON-Nordic LG trial compared R-CHOP-14 with rituximab delivered on day 1 for four cycles in one arm, and on days 1 and 8 in the comparison arm (R2-CHOP). Patients were assessed for response after four cycles, and those with progressive disease were taken off the study. The remaining patients continued on their assigned regimen for an additional four cycles and second assessment, and those who had complete responses then underwent a second randomization to rituximab maintenance or observation. Patients randomized to maintenance could receive up to 12 8-week cycles.

The second randomization was stratified by age (18-65 vs. 66-80 years), age-adjusted International Prognostic Index score, and R-CHOP regimen (one or two infusions per cycle in the first randomization).

The induction phase found no significant benefit for the additional rituximab infusion for the primary endpoint of progression-free survival, with 3-year PFS rates of 74% for R-CHOP and 71% for R2-CHOP. Respective 5-year PFS rates were 68% and 62%.

There were no differences between the arms by any of the stratification factors, and no difference in overall survival.

Dr. Lugtenburg presented results of the maintenance phase, which included all patients in complete remission at least 4 weeks after the last cycle of R-CHOP-14 who did not have rituximab-related adverse events or active infections.

A total of 195 patients were randomized to observation, and 185 to maintenance. Of this latter group, 149 patients received all 12 cycles, with a median duration of exposure of 22.5 months.

As noted, DFS, the primary endpoint for the maintenance phase, was not significantly different between the arms, with 136 events in the maintenance arm versus 134 in the observation arm. A total of 21 patients assigned to maintenance died, and 22 patients assigned to observation died during follow-up.

The respective 5-year DFS rates were 79% and 74%, a difference that was not statistically significant.

There were no significant differences between the arms in either time to relapse or death, and no difference in overall survival.

In the question-and-answer section following her talk, Marek Trnený, MD, from Charles University in Prague, pointed out that, in the NHL 13 study, which looked at rituximab maintenance for patients with DLBCL or follicular lymphoma in first remission, there was an apparent clinical benefit with rituximab maintenance for men with low International Prognostic Index scores, and asked whether Dr. Lugtenburg and colleagues had seen similar trends.

“We knew about this finding, and we really didn’t see any differences between males and females, not only in terms of efficacy, but also in terms of toxicity, they had actually the same rates of toxicity,” she said.

In NHL 13, women had a significantly higher incidence of grade 3-4 adverse events, compared with men.

The study was sponsored by HOVON, the HematoOncology Foundation for Adults in the Netherlands, with additional support from Roche. Dr. Lugtenburg reported consultancy for and research funding from Roche and others. Dr. Trnený reported advisory board activity, research support, and honoraria from Roche and others.

SOURCE: Lugtenburg PJ et al. EHA 2019, Abstract S1559.

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.