SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

msullivan@mdege.com

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

msullivan@mdege.com

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

msullivan@mdege.com

SOURCE: Murrell D et al. AAD 2019, Session S034.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

LAS VEGAS – There was no difference in first neonatal glucose level or glucose levels within the first 24 hours of life when women with gestational diabetes received strict, rather than liberalized, glucose management in labor.

Kari Oakes/MDedge News

In a study of 76 women with gestational diabetes mellitus (GDM), the mean first blood glucose level was 53 mg/dL for neonates born to the 38 mothers who received tight glucose control during labor; for those born to the 38 women who received liberalized control, mean first glucose level was 56 mg/dL (interquartile ranges, 22-85 mg/dL and 27-126 mg/dL, respectively; P = .56).

Secondary outcomes tracked in the study included the proportion of neonates whose glucose levels were low (defined as less than 40 mg/dL) at birth. This figure was identical in both groups, at 24%.

These findings ran counter to the hypothesis that Maureen Hamel, MD, and her colleagues at Brown University, Providence, R.I., had formulated – that neonates whose mothers had tight intrapartum glucose control would have lower rates of neonatal hypoglycemia than those born to women with liberalized intrapartum control.

Although the differences did not reach statistical significance, numerically more infants in the tight-control group required any intervention for hypoglycemia (45% vs. 32%; P = .35) or intravenous intervention for hypoglycemia (11% vs 0%; P = .35). Neonatal ICU admission was required for 13% of the tight-control neonates versus 3% of the liberalized-control group (P = .20).

“A protocol aimed at tight maternal glucose management in labor, compared to liberalized management, for women with GDM, did not result in a lower rate of neonatal hypoglycemia and was associated with mean neonatal glucose closer to hypoglycemia [40 mg/dL] in the first 24 hours of life,” said Dr. Hamel, discussing the findings of her award-winning abstract at the meeting presented by the Society for Maternal-Fetal Medicine.

Women were included if they were at least 18 years old with a singleton pregnancy and a diagnosis of gestational diabetes. Participants received care through a specialized program for pregnant women with diabetes; they were considered to have GDM if they had at least two abnormal values from a 100-g, 3-hour glucose tolerance test (GTT) or had a blood glucose reading of at least 200 mg/dL from a 1-hour 50-g GTT. About two-thirds of women required medical management of GDM; about 80% received labor induction at 39 weeks’ gestation.

At 36 weeks’ gestation, participants were block-randomized 1:1 to receive tight or liberalized intrapartum blood glucose control, with allocation unknown to both providers and patients until participants were admitted for delivery. Neonatal providers were blinded as to allocation throughout the admission. “In the tight glucose control group, point-of-care glucose was assessed hourly,” said Dr. Hamel. “Goal glucose levels were 70-100 [mg/dL], and treatment was initiated for a single maternal glucose greater than 100 and less than 60 [mg/dL].”

Those in the liberalized group had blood sugar checked every 4 hours in the absence of symptoms, with a goal blood glucose range of 70-120 mg/dL and treatment initiated for blood glucose over 120 or less than 60 mg/dL.

The increase in older women giving birth partly underlies the increase in GDM, said Dr. Hamel. By 35 years of age, about 15% of women will develop GDM, compared with under 6% for women giving birth between 20 and 24 years of age.

Neonatal hypoglycemia, with associated risks for neonatal ICU admission, seizures, and neurologic injury, is more common in women with GDM, said Dr. Hamel, a maternal-fetal medicine fellow.

There’s wide institutional and geographic variation in intrapartum maternal glucose management, said Dr. Hamel. Even within her own institution, blood sugar might be checked just once in labor, every 2 hours, or every hour, and the threshold for treatment might be set at a maternal blood glucose level over 100, 120, or even 200 mg/dL.

The study benefited from the fact that there was standardized antepartum GDM management in place and that 100% of outcome data were available. Also, the a priori sample size to detect significant between-group differences was obtained, and neonatal providers were blinded as to maternal glucose control strategy. Replication of the study should be both easy and feasible, said Dr. Hamel.

However, only very short-term outcomes were tracked, and the study was not powered to detect differences in such less-frequent neonatal outcomes as neonatal ICU admission.

“There is no benefit to tight maternal glucose control in labor among women with GDM,” concluded Dr. Hamel. “Our findings support glucose assessment every 4 hours, with intervention for blood glucose levels less than 60 or higher than 120 [mg/dL].”

Dr. Hamel reported no outside sources of funding and no conflicts of interest.

SOURCE: Hamel M et al. Am J Obstet Gynecol. 2019 Jan. 220;1:S36, Abstract 44.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.

In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.

Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.

Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).


Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”

They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.

The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.

Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.

SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.

Flora Kisuule, MD, SFHM, has been awarded the 2018 Excellence in Service and Professionalism Award by Johns Hopkins Bayview Medical Center, Baltimore. Dr. Kisuule is associate director of the division of hospital medicine at Johns Hopkins Bayview, assistant professor at Johns Hopkins University School of Medicine, and assistant professor in the Johns Hopkins Bloomberg School of Public Health.

Dr. Kisuule codeveloped a hospitalist fellowship program for Johns Hopkins University, which she now directs. She has served on several Society of Hospital Medicine committees and consulted on hospitalist programs around the world. Dr. Kisuule is joining the SHM Board of Directors in March 2019.

Paul Hain, DO, was promoted recently to chief medical officer and senior vice president of market delivery for Blue Cross/Blue Shield of Texas. Dr. Hain has a wealth of experience in leadership, including helping create the pediatric hospitalist program at Vanderbilt Children’s Hospital in Nashville, Tenn.

With BC/BS, Dr. Hain will oversee the region’s public relations, community investments, government relations, and lobbying. He will help sponsor Medicare and Medicaid in the state, while also supporting enterprise and marketing efforts. Dr. Hain joins BC/BS after serving as vice president and medical director of population health and network development at the Children’s Medical Center of Dallas.

Laura M. Rosch, DO, recently was selected by Kansas City University as the new campus dean in the Joplin (Mo.) College of Osteopathic Medicine. Dr. Rosch is a practicing hospitalist in Illinois, where she was chair of internal medicine at the Chicago College of Osteopathic Medicine prior to taking her current position.

Dr. Rosch will manage daily operations for the Joplin medical school, streamlining the school with the main campus. She is a former president of the Illinois Osteopathic Medicine Society and holds a master’s degree in nutrition science.

Suzan Lowry, MD, has been named health officer for Charles County, Md., by the county Department of Health and Charles County Commissioners. A longtime pediatrician with 20 years’ experience, Dr. Lowry has served as a pediatric hospitalist educator at Children’s National Medical Center in Washington, D.C.

Dr. Lowry has spent a majority of her career working on behalf of public health. Most recently, she has worked at the United States Marine Corps Quantico Health Clinic in Virginia.

Robyn Chase, DO, a staff hospitalist at Yavapai Regional Medical Center (Prescott, Ariz.), recently was selected as the hospital’s Physician of the Year for 2018.

Dr. Chase has practiced at YRMC since 2010 and is a board-certified internist. She also serves as an associate professor at the University of Arizona, Phoenix.

Kevin Dishman, MD, has been elevated to senior vice president and chief medical officer at Stormont Vail Health (Topeka, Kan.). Dr. Dishman also will be president of Stormont medical services division’s medical staff.

Dr. Dishman came to Stormont in 2000 to work as a hospitalist. Most recently, he has served as the center’s vice president of acute care services. In his new role, Dr. Dishman will be charged with, among other duties, seeking out physicians to bring to Stormont’s Topeka location.

BUSINESS MOVES

The Hazel Hawkins Memorial Hospital Women’s Center (Hollister, Calif.) recently established a relationship with Pediatrix Medical Group (Sunrise, Fla.) to provide pediatric hospitalists to help with high-risk delivery of newborns. The hospitalists also will advise Hazel Hawkins staff with regards to critical care transport and assist with the care of newborns and the treatment of child and teen patients.

Hazel Hawkins has been in operation for the past 5 years. Pediatrix hospitalists will be used as consultants for attending staff and emergency physicians and will help treat patients in emergency situations.

American Physician Partners (Brentwood, Tenn.), a national hospital medicine management services company, has acquired private physician group Progressive Medical Associates (Mesa, Ariz.). Progressive’s 37 physicians and 21 private clinicians – working at Banner Health’s 28 nonprofit hospitals covering six states – join the APP team.

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

Administering prenatal corticosteroids to women at risk for preterm birth does not appear to contribute to adverse neurocognitive function in children 6-8 years later, regardless of whether they had fetal growth restriction, a new study found.

Photodisc/Thinkstock

Women at less than 32 weeks’ gestation are recommended to receive multiple betamethasone doses if they have a high ongoing risk of preterm birth. However, concern existed regarding possible effects of these steroid doses on the infant in later childhood, particularly in cases of fetal growth restriction (FGR) because of “animal studies suggesting long-term adverse effects of treatment on neurosensory function,” Robert D. Cartwright of the University of Auckland (New Zealand), and his associates reported in JAMA Network Open.

Yet no such effects were identified in this preplanned follow-up analysis of the placebo-controlled, randomized Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS). “Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of fetal growth restriction, in view of the associated neonatal benefits and absence of later adverse effects,” the authors concluded.

The original ACTORDS study involved 982 women pregnant with 1,146 fetuses at 23 hospitals throughout Australia and New Zealand, enrolled from April 1998 to July 2004. All enrolled women were less than 32 weeks’ gestation, had received an initial course of corticosteroids, and had an ongoing risk of preterm birth at least 7 days later.

Women were randomly assigned to receive an intramuscular dose of betamethasone or saline placebo weekly until birth or preterm birth risk abated. The current follow-up, when children were 6-8 years old, was planned during the 2-year follow-up. Children underwent a pediatrician’s physical and neurologic exam, vision and hearing screening, and fine and gross motor testing. A psychologist tested children’s IQ, attention, executive function, and academic skills using standardized, validated assessment tools. Caregivers also rated children’s behavioral and emotional problems, executive function abilities, and attention in questionnaires.

Among 988 of 1,059 surviving children assessed, FGR occurred in 28% of children exposed to betamethasone and 25% in the placebo group.

For the primary outcomes, rates of disability-free survival were similar in both the placebo and betamethasone groups for children with (odds ratio, 1.1) and without FGR (OR, 1.0). Rates also were similar for death or survival with moderate to severe disability (FGR: OR, 0.9; and non-FGR: OR, 0.8).

“Some evidence suggested a differential effect for several secondary outcomes, with better scores for selective and divided attention after exposure to repeated antenatal betamethasone in children with FGR, but poorer scores for impulse control in children without FGR,” Dr. Cartwright and his associates reported. “These effects were small and of uncertain clinical significance and may reflect type I error.

“For all other measures of neurocognitive function and learning, exposure to repeated antenatal betamethasone treatment did not alter performance in midchildhood, even in the presence of FGR,” they added.

Children with FGR had an increased risk of death or moderate to severe disability, compared with children without FGR, regardless of treatment group. Those with FGR also had greater risk of motor impairment.

One possible reason for not finding adverse neurocognitive effects in the betamethasone group is “that infants with fetal growth restriction appeared to have greater benefit from repeated antenatal corticosteroid therapy, with a nearly twofold reduction in serious neonatal morbidity,” the authors surmised. “Thus, the decrease in serious postnatal complications may have counteracted any potential adverse effects of corticosteroid exposure.” But they noted a continuing concern about whether “repeated antenatal corticosteroids in FGR could increase the risk of ADHD.”

The research was funded by the National Health Medical Research Council of Australia, the Health Research Council of New Zealand and the Auckland Medical Research Foundation. One coauthor reported receiving grants from National Health and Medical Research Council of Australia, and a second coauthor received grants from the Auckland Medical Research Foundation.

SOURCE: Cartwright RD et al. JAMA Netw Open. 2019 Feb 1. doi:10.1001/jamanetworkopen.2018.7636.

Administering prenatal corticosteroids to women at risk for preterm birth does not appear to contribute to adverse neurocognitive function in children 6-8 years later, regardless of whether they had fetal growth restriction, a new study found.

Photodisc/Thinkstock

Women at less than 32 weeks’ gestation are recommended to receive multiple betamethasone doses if they have a high ongoing risk of preterm birth. However, concern existed regarding possible effects of these steroid doses on the infant in later childhood, particularly in cases of fetal growth restriction (FGR) because of “animal studies suggesting long-term adverse effects of treatment on neurosensory function,” Robert D. Cartwright of the University of Auckland (New Zealand), and his associates reported in JAMA Network Open.

Yet no such effects were identified in this preplanned follow-up analysis of the placebo-controlled, randomized Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS). “Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of fetal growth restriction, in view of the associated neonatal benefits and absence of later adverse effects,” the authors concluded.

The original ACTORDS study involved 982 women pregnant with 1,146 fetuses at 23 hospitals throughout Australia and New Zealand, enrolled from April 1998 to July 2004. All enrolled women were less than 32 weeks’ gestation, had received an initial course of corticosteroids, and had an ongoing risk of preterm birth at least 7 days later.

Women were randomly assigned to receive an intramuscular dose of betamethasone or saline placebo weekly until birth or preterm birth risk abated. The current follow-up, when children were 6-8 years old, was planned during the 2-year follow-up. Children underwent a pediatrician’s physical and neurologic exam, vision and hearing screening, and fine and gross motor testing. A psychologist tested children’s IQ, attention, executive function, and academic skills using standardized, validated assessment tools. Caregivers also rated children’s behavioral and emotional problems, executive function abilities, and attention in questionnaires.

Among 988 of 1,059 surviving children assessed, FGR occurred in 28% of children exposed to betamethasone and 25% in the placebo group.

For the primary outcomes, rates of disability-free survival were similar in both the placebo and betamethasone groups for children with (odds ratio, 1.1) and without FGR (OR, 1.0). Rates also were similar for death or survival with moderate to severe disability (FGR: OR, 0.9; and non-FGR: OR, 0.8).

“Some evidence suggested a differential effect for several secondary outcomes, with better scores for selective and divided attention after exposure to repeated antenatal betamethasone in children with FGR, but poorer scores for impulse control in children without FGR,” Dr. Cartwright and his associates reported. “These effects were small and of uncertain clinical significance and may reflect type I error.

“For all other measures of neurocognitive function and learning, exposure to repeated antenatal betamethasone treatment did not alter performance in midchildhood, even in the presence of FGR,” they added.

Children with FGR had an increased risk of death or moderate to severe disability, compared with children without FGR, regardless of treatment group. Those with FGR also had greater risk of motor impairment.

One possible reason for not finding adverse neurocognitive effects in the betamethasone group is “that infants with fetal growth restriction appeared to have greater benefit from repeated antenatal corticosteroid therapy, with a nearly twofold reduction in serious neonatal morbidity,” the authors surmised. “Thus, the decrease in serious postnatal complications may have counteracted any potential adverse effects of corticosteroid exposure.” But they noted a continuing concern about whether “repeated antenatal corticosteroids in FGR could increase the risk of ADHD.”

The research was funded by the National Health Medical Research Council of Australia, the Health Research Council of New Zealand and the Auckland Medical Research Foundation. One coauthor reported receiving grants from National Health and Medical Research Council of Australia, and a second coauthor received grants from the Auckland Medical Research Foundation.

SOURCE: Cartwright RD et al. JAMA Netw Open. 2019 Feb 1. doi:10.1001/jamanetworkopen.2018.7636.

Administering prenatal corticosteroids to women at risk for preterm birth does not appear to contribute to adverse neurocognitive function in children 6-8 years later, regardless of whether they had fetal growth restriction, a new study found.

Photodisc/Thinkstock

Women at less than 32 weeks’ gestation are recommended to receive multiple betamethasone doses if they have a high ongoing risk of preterm birth. However, concern existed regarding possible effects of these steroid doses on the infant in later childhood, particularly in cases of fetal growth restriction (FGR) because of “animal studies suggesting long-term adverse effects of treatment on neurosensory function,” Robert D. Cartwright of the University of Auckland (New Zealand), and his associates reported in JAMA Network Open.

Yet no such effects were identified in this preplanned follow-up analysis of the placebo-controlled, randomized Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS). “Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of fetal growth restriction, in view of the associated neonatal benefits and absence of later adverse effects,” the authors concluded.

The original ACTORDS study involved 982 women pregnant with 1,146 fetuses at 23 hospitals throughout Australia and New Zealand, enrolled from April 1998 to July 2004. All enrolled women were less than 32 weeks’ gestation, had received an initial course of corticosteroids, and had an ongoing risk of preterm birth at least 7 days later.

Women were randomly assigned to receive an intramuscular dose of betamethasone or saline placebo weekly until birth or preterm birth risk abated. The current follow-up, when children were 6-8 years old, was planned during the 2-year follow-up. Children underwent a pediatrician’s physical and neurologic exam, vision and hearing screening, and fine and gross motor testing. A psychologist tested children’s IQ, attention, executive function, and academic skills using standardized, validated assessment tools. Caregivers also rated children’s behavioral and emotional problems, executive function abilities, and attention in questionnaires.

Among 988 of 1,059 surviving children assessed, FGR occurred in 28% of children exposed to betamethasone and 25% in the placebo group.

For the primary outcomes, rates of disability-free survival were similar in both the placebo and betamethasone groups for children with (odds ratio, 1.1) and without FGR (OR, 1.0). Rates also were similar for death or survival with moderate to severe disability (FGR: OR, 0.9; and non-FGR: OR, 0.8).

“Some evidence suggested a differential effect for several secondary outcomes, with better scores for selective and divided attention after exposure to repeated antenatal betamethasone in children with FGR, but poorer scores for impulse control in children without FGR,” Dr. Cartwright and his associates reported. “These effects were small and of uncertain clinical significance and may reflect type I error.

“For all other measures of neurocognitive function and learning, exposure to repeated antenatal betamethasone treatment did not alter performance in midchildhood, even in the presence of FGR,” they added.

Children with FGR had an increased risk of death or moderate to severe disability, compared with children without FGR, regardless of treatment group. Those with FGR also had greater risk of motor impairment.

One possible reason for not finding adverse neurocognitive effects in the betamethasone group is “that infants with fetal growth restriction appeared to have greater benefit from repeated antenatal corticosteroid therapy, with a nearly twofold reduction in serious neonatal morbidity,” the authors surmised. “Thus, the decrease in serious postnatal complications may have counteracted any potential adverse effects of corticosteroid exposure.” But they noted a continuing concern about whether “repeated antenatal corticosteroids in FGR could increase the risk of ADHD.”

The research was funded by the National Health Medical Research Council of Australia, the Health Research Council of New Zealand and the Auckland Medical Research Foundation. One coauthor reported receiving grants from National Health and Medical Research Council of Australia, and a second coauthor received grants from the Auckland Medical Research Foundation.

SOURCE: Cartwright RD et al. JAMA Netw Open. 2019 Feb 1. doi:10.1001/jamanetworkopen.2018.7636.

The hippocampal functional connectivity (FC) found in patients with major depressive disorder is different from the FC found in patients with bipolar disorder, an analysis of functional MRI data shows.

“These findings may assist investigators in attempting to distinguish mood disorders by using fMRI data,” Ahmed Ameen Fateh and his associates wrote in Psychiatry Research: Neuroimaging.

Mr. Fateh and his associates recruited 29 participants with depression and 30 with bipolar disorder, from a mental health center of Chengdu, Sichuan, China. An additional 30 healthy controls were recruited through advertisements, reported Mr. Fateh, a doctoral student at the University of Electronic Science and Technology of China, Chengdu.

Using one-way analysis of variance, the investigators looked at possible differences in the participants’ hippocampal FC. The results showed that some regions exhibited significant differences in the hippocampal FC among the patients with major depression and bipolar disorder.

If their results could be replicated, the researchers wrote, “such differences may yield future trends towards improving the clinical differentiation between these two types of depression with significant therapeutic and prognostic implications.”

cpalmer@mdedge.com

SOURCE: Fateh AA et al. Psychiatry Res Neuroimaging. 2019 Jan 12. doi: 10.1016/j.pscychresns.2019.01.004.

The hippocampal functional connectivity (FC) found in patients with major depressive disorder is different from the FC found in patients with bipolar disorder, an analysis of functional MRI data shows.

“These findings may assist investigators in attempting to distinguish mood disorders by using fMRI data,” Ahmed Ameen Fateh and his associates wrote in Psychiatry Research: Neuroimaging.

Mr. Fateh and his associates recruited 29 participants with depression and 30 with bipolar disorder, from a mental health center of Chengdu, Sichuan, China. An additional 30 healthy controls were recruited through advertisements, reported Mr. Fateh, a doctoral student at the University of Electronic Science and Technology of China, Chengdu.

Using one-way analysis of variance, the investigators looked at possible differences in the participants’ hippocampal FC. The results showed that some regions exhibited significant differences in the hippocampal FC among the patients with major depression and bipolar disorder.

If their results could be replicated, the researchers wrote, “such differences may yield future trends towards improving the clinical differentiation between these two types of depression with significant therapeutic and prognostic implications.”

cpalmer@mdedge.com

SOURCE: Fateh AA et al. Psychiatry Res Neuroimaging. 2019 Jan 12. doi: 10.1016/j.pscychresns.2019.01.004.

The hippocampal functional connectivity (FC) found in patients with major depressive disorder is different from the FC found in patients with bipolar disorder, an analysis of functional MRI data shows.

“These findings may assist investigators in attempting to distinguish mood disorders by using fMRI data,” Ahmed Ameen Fateh and his associates wrote in Psychiatry Research: Neuroimaging.

Mr. Fateh and his associates recruited 29 participants with depression and 30 with bipolar disorder, from a mental health center of Chengdu, Sichuan, China. An additional 30 healthy controls were recruited through advertisements, reported Mr. Fateh, a doctoral student at the University of Electronic Science and Technology of China, Chengdu.

Using one-way analysis of variance, the investigators looked at possible differences in the participants’ hippocampal FC. The results showed that some regions exhibited significant differences in the hippocampal FC among the patients with major depression and bipolar disorder.

If their results could be replicated, the researchers wrote, “such differences may yield future trends towards improving the clinical differentiation between these two types of depression with significant therapeutic and prognostic implications.”

cpalmer@mdedge.com

SOURCE: Fateh AA et al. Psychiatry Res Neuroimaging. 2019 Jan 12. doi: 10.1016/j.pscychresns.2019.01.004.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

SEATTLE – Treatment of hepatitis C virus (HCV) with new direct-acting antiviral (DAA) regimens is associated with improved glucose control and reduced incidence of type 2 diabetes when compared to treatment with pegylated interferon/ribavirin (PEG/RBV ) and untreated controls, according to a new analysis of the Electronically Retrieved Cohort of HCV Infected Veterans.

Jim Kling/MDedge News

“Previously, people who had diabetes were considered slightly more difficult to treat because their virologic response was a little lower, but now this is not the case, and we have the added benefit of reducing the incidence of diabetes,” said Adeel Butt, MD, professor of medicine and health care policy and research at Weill Cornell Medicine, New York and Qatar, in an interview. Dr. Butt presented the study at the Conference on Retroviruses & Opportunistic Infections.

The incidence of diabetes dropped in the overall treated cohort, compared with untreated patients, but this benefit was driven by the effect of DAAs, as there was no significant difference between PEG/RBV–treated patients and controls. “It’s another reason to argue with people who make it difficult to treat. Our biggest barriers to treating everyone with hepatitis C has to do with reimbursement and the capacity of the health care system, and this is another reason that we need to overcome those barriers. It’s an important insight that provides one more reason to try to continue to eradicate hepatitis C in our population,” said Robert Schooley, MD, professor of medicine at the University of California, San Diego, in an interview.

Patients may also need some reassurance, given concerns that have arisen over the potential for older regimens to cause diabetes. Dr. Butt cited an example of a patient who has an acute myocardial infarction, has a high body mass, and wants to know if DAAs will help or hurt them. “We see [such patients] frequently. This is pretty reassuring not only that DAAs don’t increase risk, but they actually decrease the risk of diabetes as opposed to older treatments. There is a growing body of evidence that non–liver [related conditions] significantly improve with treatment,” he said.

The results could also help prioritize patients for treatment. “It may be important to the patients who are at elevated risk of developing diabetes. They may need to be monitored more closely and offered treatment earlier, perhaps, but that requires more study,” said Dr. Butt.

The researchers excluded patients with HIV or hepatitis B virus, and those who had prevalent diabetes. The cohort included 26,043 treated patients and 26,043 propensity score–matched untreated control patients. Treated patients underwent at least 8 weeks of DAA or 24 weeks of PEG/RBV. Demographically, 54% of patients were white, 29% were black, 3% were Hispanic, and 96% of the patients were male. About one-third had a body mass index of 30 or above.

The incidence of diabetes was 20.6 per 1,000 person-years of follow-up among untreated patients, compared with 15.5 among treated patients (P less than .0001). The incidence was 19.8 in patients treated with PEG/RBV (P =.39) and 9.9 in those treated with DAAs (P less than. 001; hazard ratio, 0.48; P less than .0001). The incidence of diabetes in those with a sustained viral response (SVR) was 13.3 per 1,000 person-years, compared with 19.2 in patients with no SVR (P less than .0001). The incidence of diabetes was lower in treated patients regardless of baseline FIB-4 (Fibrosis-4, a liver fibrosis score) levels.

The study was funded by Gilead. Dr. Butt has had research grants from Gilead and Dr. Schooley is on Gilead’s scientific advisory board.

SOURCE: A Butt et al. CROI 2019. Abstract 88.

Frontline treatment with bendamustine plus rituximab outperformed other rituximab-based chemotherapy regimens in long-term follow-up of mantle cell and indolent lymphoma patients in the BRIGHT study.

The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.

While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.

“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.

Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.

For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.

The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).

Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).

The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.

Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.

“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.

In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.

This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.

mschneider@mdedge.com

SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.

Frontline treatment with bendamustine plus rituximab outperformed other rituximab-based chemotherapy regimens in long-term follow-up of mantle cell and indolent lymphoma patients in the BRIGHT study.

The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.

While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.

“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.

Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.

For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.

The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).

Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).

The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.

Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.

“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.

In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.

This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.

mschneider@mdedge.com

SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.

Frontline treatment with bendamustine plus rituximab outperformed other rituximab-based chemotherapy regimens in long-term follow-up of mantle cell and indolent lymphoma patients in the BRIGHT study.

The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.

While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.

“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.

Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.

For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.

The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).

Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).

The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.

Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.

“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.

In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.

This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.

mschneider@mdedge.com

SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.