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PsA patients had durable responses after 1 year of IV golimumab treatment
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
, according to follow-up results of a randomized clinical trial.
The improvements in joint disease, skin disease, and health-related quality of life seen at 24 weeks in the phase 3 GO-VIBRANT study were maintained at this 52-week follow-up, according to M. Elaine Husni, MD, of the Cleveland Clinic, and coinvestigators.
Patients who crossed over to golimumab treatment after 24 weeks of placebo had similar rates of clinical response at 52 weeks, while patients receiving concomitant methotrexate had similar ACR response rates, compared with patients on golimumab monotherapy, Dr. Husni and colleagues reported.
Many patients who were not ACR20 responders at week 52 nevertheless had improvements in skin disease, enthesitis, and dactylitis, an exploratory analysis showed.
“These factors may have contributed to these patients remaining in the trial and continuing golimumab therapy despite not achieving an ACR20 response,” wrote Dr. Husni and coauthors. The report is in Arthritis Care & Research.
The Food and Drug Administration approved a once-monthly subcutaneous formulation of golimumab (Simponi) in 2009 for treatment of moderate to severe active psoriatic arthritis, rheumatoid arthritis, and active ankylosing spondylitis. The intravenous formulation of this TNF inhibitor (Simponi Aria) received a psoriatic arthritis indication in 2017 based on GO-VIBRANT data. Published results at the time showed that compared with placebo, intravenous golimumab given as a 2-mg/kg infusion at weeks 0, 4, and then every 8 weeks produced greater improvements in psoriatic arthritis signs and symptoms and less radiographic progression through week 24 of the study, and had adverse events consistent with other TNF inhibitors, according to investigators.
The follow-up report includes efficacy and safety data for golimumab-treated patients beyond 24 weeks, as well as data for patients on the placebo arm, who crossed over to receive golimumab at week 24, week 28, and then every 8 weeks thereafter.
The results show ACR response rates were maintained from week 24 to 52 in golimumab-treated patients, and were similar in the placebo crossover patients. The ACR20, ACR50, and ACR70 response rates in the golimumab group were 76.8%, 58.1%, and 38.6%, respectively, while in the crossover group, they were 77.0%, 53.6%, and 33.9%, respectively.
Radiographic progression was measured using van der Heijde-Sharp (vdH-S) score with modifications for psoriatic arthritis. The mean change in vdH-S score at 24 weeks was –0.4 and 2.0 in the golimumab and placebo groups, respectively; by week 52, the mean change was –0.5 and 0.8 for golimumab and placebo crossover.
Infection was the most common adverse event throughout 60 weeks of safety evaluation, occurring in 22.8% of all golimumab-treated patients, investigators said. Four infusion reactions occurred following golimumab administration, though none were considered serious or severe.
The GO-VIBRANT study, which comprised 480 adults, had limited follow-up and was not powered to identify rare safety events, investigators said.
“However, the totality of results through 1 year of the GO-VIBRANT study show a durable response to IV golimumab 2 mg/kg across several clinical efficacy, HRQoL, and radiographic endpoints with no new safety signals,” they concluded.
Study authors reported disclosures with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Janssen, Novartis, Pfizer, Sanofi, and UCB. Several study authors reported current or former employment with Janssen Research & Development and stock or stock options in Johnson & Johnson.
SOURCE: Husni ME et al. Arthritis Care Res. 2019 Apr 12. doi: 10.1002/acr.23905.
FROM ARTHRITIS CARE & RESEARCH
Zika knowledge, preparedness low among U.S. pediatricians
BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.
“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.
“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.
But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.
“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”
Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.
Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.
However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.
Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.
Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.
Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).
Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.
“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.
“ but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.
Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.
The research was funded by the AAP and CDC.
BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.
“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.
“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.
But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.
“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”
Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.
Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.
However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.
Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.
Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.
Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).
Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.
“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.
“ but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.
Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.
The research was funded by the AAP and CDC.
BALTIMORE – U.S. pediatricians feel comfortable providing patients with preventive information and travel advice related to Zika, but few feel prepared when it comes to testing and management of infants exposed prenatally to Zika infections, a study found.
“Areas where pediatricians were less likely to report preparedness included recommending testing, providing data to the Centers for Disease Control and Prevention’s Zika Pregnancy Registry, managing infants exposed to Zika prenatally, and informing parents of social services for Zika-infected infants,” senior author Amy J. Houtrow, MD, MPH, PhD, and colleagues reported at the Pediatric Academic Societies annual meeting.
“Results indicate that additional education efforts are needed to grow the overall Zika knowledge of pediatricians and boost preparedness, particularly around recommending Zika testing and providing data to CDC,” they concluded.
But these findings are not surprising given how rare congenital Zika virus syndrome is, explained Dr. Houtrow, an associate professor of physical medicine and rehabilitation and pediatrics at the University of Pittsburgh.
“For most rare conditions, pediatricians report better general than specific knowledge,” Dr. Houtrow said in an interview. “We expect pediatricians have a broad range of knowledge for a multitude of conditions and to be well versed in the care of infants and children with common conditions, coupled with the ability to access knowledge and expertise about rarer conditions such as congenital Zika syndrome.”
Dr. Houtrow and associates drew their findings from the 2018 AAP Periodic Survey of Fellows, which includes both primary care physicians and neonatologists. The survey’s response rate was 42%, with 672 of 1,599 surveys returned, but the researchers limited their analysis to 576 postresidency respondents who were providing direct patient care.
Overall, 39% of physicians reported being knowledgeable about Zika virus, and 47% said they wanted to learn more. More than half of responding doctors (57%) reported feeling moderately or very prepared when it came to informing patients of preventive measures to reduce risk of Zika infection, and nearly half (49%) felt confident about giving patients travel advice.
However, physicians’ preparedness gradually dropped for clinical situations requiring more direct experience with Zika. For example, 37% felt moderately or very prepared to provide clinical referrals for infant patients with an infection, and 33% felt prepared to talk with pregnant women about the risks of birth defects from Zika infection.
Just one in five physicians (22%) felt prepared for recommending Zika virus testing, and 16% felt prepared about providing data to the CDC’s U.S. Zika Pregnancy Registry or managing infants who had been prenatally exposed to Zika infection. Only 15% felt they had the preparedness to tell parents about social services for Zika-affected infants.
Preparedness did not differ by gender, specialty, practice setting, hours worked per week, or population density (urban, rural and suburban). However, differences did appear based on respondents’ age and U.S. region.
Older doctors reported greater knowledge about Zika than younger doctors. Compared with those aged 39 years or younger, those aged 40-49 and 50-59 reported feeling more knowledgeable (adjusted odds ratio, 1.74 and 1.72, respectively; P less than .05). The odds of feeling more knowledgeable was nearly triple among those aged at least 60 years, compared with those under 40 (aOR, 2.92; P less than .001).
Those practicing in the Northeast United States (aOR, 2.19; P less than .01) and in the South (aOR, 1.74; P less than .05) also reported feeling more knowledgeable than those in the West or Midwest.
“This makes sense because infants with a history of prenatal exposure to the Zika Virus are more likely to be seen in practices with more immigrants from the Caribbean and Latin America,” Dr. Houtrow said in an interview.
“ but the urgency of the need for education about Zika virus has diminished because the rates of new congenital Zika syndrome have dropped,” she continued.
Study limitations include the inability to generalize the findings beyond U.S. members of the AAP and the possibility that nonrespondents differed from respondents in terms of Zika knowledge and preparedness.
The research was funded by the AAP and CDC.
REPORTING FROM PAS 2019
Fecal microbiota transplant shows promise for hepatic encephalopathy
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
VIENNA –
The oral fecal microbiota transplant (FMT), modeled on guideline-directed treatment for Clostridium difficile (Clin Infect Dis. 2018 April 1;66[7]:e1-48), was linked with a cut in hospitalizations and serious adverse events, as well as a clinically meaningful improvement in a cognitive measure specific for hepatic encephalopathy, Jasmohan S. Bajaj, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Given the preliminary scope of the study, the next step is to assess the treatment in more patients and to evaluate delivery of the FMT specifically to the upper or lower gastrointestinal tract, said Dr. Bajaj, a hepatologist at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond.
The study included 20 patients with recurrent hepatic encephalopathy (RHE) and a history of at least two encephalopathy episodes despite treatment with lactulose and rifaximin (Xifaxan). After a baseline assessment, 10 patients received a single, oral dose of FMT contained in 15 capsules and composed of fecal material from the OpenBiome collection, and 10 patients received placebo capsules. All of the FMT material came from a single donor and contained a high level of beneficial microbial types, specifically Lachnospiraceae and Ruminococcaceae species. Patients averaged 64 years of age.
During 5 months of follow-up, 6 of the 10 placebo patients had a serious adverse event versus 1 of the 10 patients treated with an active FMT; altogether, there were 11 serious adverse events among the placebo patients versus only 1 event among the FMT patients, Dr. Bajaj reported. Three patients in the control arm had a total of seven hepatic encephalopathy events, compared with a single patient with one event in the intervention arm.
Enrolled patients also underwent two cognitive tests at baseline and during follow-up. Using a Stroop smartphone app (EncephalApp) designed to assess patients with RHE (Hepatology. 2013 Sept;58[3]:1122-32), the researchers found an average 51-second improvement in OffTime+OnTime, a statistically significant and clinically meaningful improvement in the patients treated with FMT, whereas the control patients showed no statistically significant change in this parameter. The second cognitive measure was the average performance by patients using the Psychometric Hepatic Encephalopathy Score (Curr Gastroenterol Rep. 2014 Jan;16[1]:362), which showed no significant change after treatment in either study arm. The actively treated patients also showed favorable changes in the microbial composition of their stool and mucosa, as well as an enhanced small intestinal barrier, following treatment, Dr. Bajaj said.
SOURCE: Bajaj JS et al. J Hepatol. 2019 April;70[1]:e55.
REPORTING FROM ILC 2019
Vaginal brachytherapy more toxic than pelvic RT in endometrial carcinoma
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
, according to results from a phase 3 trial.
The GOG-0249 study comprised 601 patients with high-intermediate– and high-risk early-stage endometrial carcinoma who were randomized in a 1:1 fashion to receive vaginal cuff brachytherapy plus paclitaxel and carboplatin or pelvic RT every 21 days for a total of three cycles.
Those in the brachytherapy group received treatment at both high and low-dosing rates. Paclitaxel was given at a dose of 175 mg/m2 infused over 3 hours, succeeded by carboplatin (area under the curve, 6) infused over 45 minutes. Pelvic RT was provided at a dose of 45 to 50.4 Gy over a period of 5-6 weeks.
“The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,” wrote Marcus E. Randall, MD, of the University of Kentucky, Lexington, and colleagues. The report is in the Journal of Clinical Oncology.
Additional outcomes measured were overall survival and acute toxicity.
After analysis, the researchers found that vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month RFS (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). Also, there was no significant difference for overall survival (HR, 1.04; 90% confidence limit, 0.71-1.52).
With respect to safety, acute adverse events were more common and severe in the vaginal brachytherapy plus chemotherapy group. However, “differences in late toxicity were minimal,” Dr. Randall and colleagues reported.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma,” they wrote. “Novel combinations, dose intensification, and additional translational research represent potential paths forward.”
The study was supported by grant funding from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. The authors reported financial affiliations with AstraZeneca, Genentech, Genmab, Janssen, Johnson & Johnson, Tesaro, and several others.
SOURCE: Randall ME et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01575.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Damage of the Lateral Geniculate Nucleus in MS
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Key clinical point: Lateral geniculate nucleus (LGN) volume loss in multiple sclerosis (MS) indicates structural damage with potential functional relevance.
Major finding: LGN volume was reduced in patients with relapsing-remitting MS vs healthy controls and was associated with ganglion cell-inner plexiform layer (GC-IPL) thickness and correlated with optic radiation (OR) lesion volume.
Study details: A cross-sectional study of 34 patients with relapsing-remitting MS and 33 matched healthy controls.
Disclosures: The lead author received funding for speaker or travel honoraria from Sanofi-Genzyme, Bayer AG, Teva, UCB-Pharma AG, and Hoffmann-La Roche.
Citation: Papadopoulou, et al. Neurology. doi:10.1212/WNL.0000000000007450.
Survey of MS Patients Reveals Pregnancy-Related Concerns
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
Key clinical point: Patients with multiple sclerosis report a wide range of concerns about family planning and pregnancy.
Major finding: Of the 137 respondents who did not become pregnant following diagnosis, 22 (16%) indicated that their decision was driven by multiple sclerosis–related concerns, including MS worsening with pregnancy (64%).
Study details: A survey of 174 women with confirmed MS diagnosis who received care at the University of Virginia Medical Center.
Disclosures: The study was supported by the ziMS Foundation.
Citation: Engel CE et al. ACTRIMS Forum 2019, Poster 307.
High pCR rate in HPV+ HNSCC with nivolumab/SBRT
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
ATLANTA – For patients with locally advanced head and neck squamous cell carcinomas positive for human papillomavirus type 16, neoadjuvant therapy with the immune checkpoint inhibitor nivolumab combined with stereotactic body radiation therapy (SBRT) was associated with high response rates and a lower toxicity profile compared with the current standard of care, results of a phase 1/1b study suggest.
All of five patients treated with SBRT doses of 8 Gy per day for 5 days (40 Gy total) had pathologic complete responses (pCR), as did four of five patients treated at a deescalated SBRT dose of 8 Gy on alternating days for 3 days (24 Gy total), reported Rom S. Leidner, MD, of Providence Cancer Center in Portland, Ore.
“We’ve met the primary endpoint. This approach certainly was safe as far as not preventing definitive surgery. The potency was much greater than expected, with a pCR rate of 90% and a major response in 100% of patients,” he said at the annual meeting of the American Association for Cancer Research.
Dr. Leidner and colleagues are investigating therapies for locally advanced HPV-associated head and neck squamous cell carcinoma (HNSCC) that are as effective as but less toxic than the current standard of care: definitive chemoradiotherapy or surgery followed by risk-adapted adjuvant radiotherapy with or without chemotherapy.
They enrolled 10 patients, all men, with a mean age of 64.5 years. Seven patients had HPV16-positive oropharyngeal HNSCC, and three had unknown primary HNSCC (HPV-positive lymph nodes in the neck without an identifiable mucosal primary site). All patients had clinical indications for adjuvant radiotherapy or upfront transoral robotic surgery (TORS) but were ineligible because of tumor size.
The patients were assigned to one of two dose-finding cohorts in groups of five each to receive nivolumab (Opdivo) 240 mg intravenously every other week for three cycles prior to surgery, with SBRT to gross tumor volume plus 3 mm delivered between the first and second doses of nivolumab.
One cohort of patients received SBRT 8 Gy daily for 5 consecutive days (Monday-Friday), and the other received deescalated SBRT 8 Gy delivered on alternating days (Monday, Wednesday, Friday).
Patients underwent surgery 5 weeks after SBRT, and 4 weeks after surgery were started on adjuvant nivolumab 480 mg IV every 4 weeks for three cycles.
The trial met its primary endpoint of fewer than one-third of patients having an unplanned surgical delay. None of the 10 patients required a surgical delay, in fact.
Although all patients had radiologic evidence of tumor shrinkage prior to surgery, there were no complete responses according to Response Criteria in Solid Tumors (RECIST, version 1.1). Seven patients had a partial response (PR), and three had stable disease.
Dr. Leidner noted that when a patient with stable disease according to RECIST went to surgery “we found a [pCR] in the primary site, and residual cancer in the neck nodes with less than 10% viable tumor cells and evidence of immune eradication.”
As noted, all five patients in the 40-Gy dose group had complete pathologic responses, as did four of the five patients in the deescalated dose group. The remaining patient in this group had a major pathologic response, with less than 10% residual tumor.
“The secondary tissue endpoint far exceeded our expectations on this trial,” Dr. Leidner said.
There were no reports of acute toxicity in the neoadjuvant phase, but delayed mucositis (grade 1 or 2) and immune-related grade 1 dermatologic and rhinitis events were seen. Mucositis resolved by week 4 in all patients, at least 2 weeks before surgery.
Postoperative delayed toxicities up to grade 3 were seen, with delays in mucosal healing in patients who underwent mucosal resections; there were no cases of delayed healing among patients who underwent neck dissection only.
Grade 3 oropharyngeal pain requiring opiates for more than 4 weeks after surgery was seen in both cohorts, but lasted longer among patients in the 8-Gy-times-5 cohort.
Half of all patients were found to have adrenal insufficiency, a rate higher than that previously reported with the use of anti-PD-1 immune checkpoint inhibitors in HNSCC, Dr. Leidner said.
“Clinically we’re seeing, as one might expect, substantially reduced xerostomia and ageusia, but that was not formally measured,” he said.
Based on the study findings, investigations are proceeding at the deescalated dose.
Invited discussant Christine H. Chung, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, did not appear to share Dr. Leidner’s enthusiasm for the approach, saying that “overall, path CR in already resectable patients with an extremely high cure rate may not be clinically meaningful.”
She said that the role of adjuvant nivolumab following neoadjuvant nivolumab, radiotherapy, and surgery in HPV-positive patients is unclear, and that “the approach may be more suitable for HPV-negative patients with poor prognosis and in need of treatment intensification.”
Providence Cancer Center sponsored the study. Dr. Leidner reported having no relevant disclosures. Dr. Chung reported research funding from Lilly Oncology, and advisory board honoraria from BMS, CUE, and Ignyta.
SOURCE: Leidner RS et al. AACR 2019, Abstract CT182.
REPORTING FROM AACR 2019
Report card may foretell achalasia surgery outcomes
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
REPORTING FROM SAGES 2019
Reducing sepsis mortality
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
The CDC estimates that 1.7 million people in the United States acquire sepsis annually; sepsis accounts for nearly 270,000 patient deaths per year.
Decreasing mortality and improving patient outcomes requires early detection and appropriate timely treatment. The Joint Commission Center for Transforming Healthcare’s recent sepsis project demonstrated this by analyzing root causes and reducing sepsis mortality with five leading hospitals by an aggregate of nearly 25%.
“Most organizations can tell you how they are doing with regard to whether or not they are ordering lactates or fluids, but many can’t tell you where in the process these elements are failing,” said Kelly Barnes, Black Belt III, Joint Commission Center for Transforming Healthcare. “For instance, is the issue in ordering lactates, drawing lactates, or getting the results of lactates in a timely manner? The key is to understand where in the process things are breaking down to identify what solutions an organization needs to put in place.”
During the Joint Commission project, one organization found that patients had inadequate fluid resuscitation due to staff fear of fluid overload, while another organization found they had issues with fluids being disconnected when patients were taken for tests and then not reconnected – different problems that needed different solutions.
The Joint Commission Center for Transforming Healthcare is currently developing a Targeted Solutions Tool® (TST®), scheduled for release in 2019, to help organizations determine their issues with sepsis recognition and barriers to meeting sepsis bundle element requirements and implement targeted solutions to address their specific issues. The tool will be available free of charge to all Joint Commission-accredited customers.
Reference
1. “Hospital-Wide Sepsis Project Reduces Mortality by Nearly 25 Percent,” Kelly Barnes, The Joint Commission Center for Transforming Healthcare. 2018, Sep 25.
Plasma Metabolome Analysis in Migraine
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.
In a large-scale plasma metabolome analysis, metabolic profiling of plasma yielded alterations in high-density lipoprotein (HDL) metabolism in patients with migraine and decreased omega-3 fatty acids only in male migraineurs, a new study found. Researchers sought to identify a plasma metabolomic biomarker signature for migraine. Plasma samples from 8 Dutch cohorts (n=10,153: 2800 migraine patients and 7353 controls) were profiled on a H-NMR-based metabolomics platform to quantify 146 individual metabolites and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Among the findings:
- Decreases in the level of apolipoprotein A1 and free cholesterol total lipid ratio present in small HDL subspecies were associated with migraine status.
- A decreased level of omega-3 fatty acids was associated with migraine in male participants only.
- Global test analysis supported that HDL traits were associated with migraine status.
Onderwater GLJ, Ligthart L, Bot M, et al. Large-scale metabolome analysis reveals alterations in HDL metabolism in migraine. [Published online ahead of print April 3, 2019]. Neurology. doi:10.1212/WNL.0000000000007313.