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Single-dose influenza drug baloxavir similar to oseltamivir in efficacy
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Single-dose influenza antiviral baloxavir shows efficacy similar to that of oseltamivir.
Major finding: Baloxavir shows similar time to alleviation of influenza symptoms compared with oseltamivir, but greater reductions in viral load.
Study details: Phase 2 and phase 3 randomized controlled trials in 389 and 1,366 otherwise healthy patients with influenza.
Disclosures: The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
Source: Hayden F et al. N Engl J Med 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
Service, please: Hospital setting matters for pneumonia
the National Center for Health Statistics (NCHS) reported.
The percentages were not as close, however, for other diagnostic services. Inpatient stays were much more likely than ED encounters to involve bacteriology and microbiology testing (75.3% vs. 31.2%), CT scans (41.2% vs. 11.5%), and pulmonary function tests (33.7% vs. 9.8%), investigators from the NCHS said.
The age distribution of the two patient populations also were quite different, with those aged 65 years and older making up the largest share (46%) of pneumonia inpatients and the 15-and-under group representing the largest proportion (47%) of ED visits. For the inpatient setting, the smallest age group was those aged 15-44 years (10%), and for the ED it was those aged 65 years and older (14%), they reported.
The National Hospital Care Survey “is not yet nationally representative,” the NCHS investigators wrote – the overall sample for 2014 consisted of 581 hospitals – but “the number of encounters and the inclusion of [personally identifiable information] allow an example of analysis that was not previously possible.”
the National Center for Health Statistics (NCHS) reported.
The percentages were not as close, however, for other diagnostic services. Inpatient stays were much more likely than ED encounters to involve bacteriology and microbiology testing (75.3% vs. 31.2%), CT scans (41.2% vs. 11.5%), and pulmonary function tests (33.7% vs. 9.8%), investigators from the NCHS said.
The age distribution of the two patient populations also were quite different, with those aged 65 years and older making up the largest share (46%) of pneumonia inpatients and the 15-and-under group representing the largest proportion (47%) of ED visits. For the inpatient setting, the smallest age group was those aged 15-44 years (10%), and for the ED it was those aged 65 years and older (14%), they reported.
The National Hospital Care Survey “is not yet nationally representative,” the NCHS investigators wrote – the overall sample for 2014 consisted of 581 hospitals – but “the number of encounters and the inclusion of [personally identifiable information] allow an example of analysis that was not previously possible.”
the National Center for Health Statistics (NCHS) reported.
The percentages were not as close, however, for other diagnostic services. Inpatient stays were much more likely than ED encounters to involve bacteriology and microbiology testing (75.3% vs. 31.2%), CT scans (41.2% vs. 11.5%), and pulmonary function tests (33.7% vs. 9.8%), investigators from the NCHS said.
The age distribution of the two patient populations also were quite different, with those aged 65 years and older making up the largest share (46%) of pneumonia inpatients and the 15-and-under group representing the largest proportion (47%) of ED visits. For the inpatient setting, the smallest age group was those aged 15-44 years (10%), and for the ED it was those aged 65 years and older (14%), they reported.
The National Hospital Care Survey “is not yet nationally representative,” the NCHS investigators wrote – the overall sample for 2014 consisted of 581 hospitals – but “the number of encounters and the inclusion of [personally identifiable information] allow an example of analysis that was not previously possible.”
Opioid Prescribing May Need a Behavioral “Nudge”
When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.
Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.
In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.
Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.
"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."
When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.
Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.
In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.
Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.
"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."
When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.
Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.
In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.
Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.
"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."
Community-based therapy improved asthma outcomes in African American teens
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
, according to results published in Pediatrics.
In a study of 167 African American patients aged 12-16 years, the 84 randomly assigned to Multisystemic Therapy–Health Care (MST-HC) had greater improvement in forced expiratory volume in 1 second (FEV1) over time, compared with the 83 patients randomly assigned to family support (FS) therapy (beta = 0.097, t[164.27] = 2.52; P = .01). Improvements in secondary outcomes also were observed in this group, reported Sylvie Naar, PhD, of Florida State University, Tallahassee, and her coauthors.
They studied African American adolescents with moderate to severe persistent asthma who resided in a home setting with a caregiver and were at high risk for poorly controlled asthma. Families were randomized to either MST-HC (84 patients) or FS (83 patients) based on severity of urgent care use, and follow-up was completed 7 and 12 months after baseline assessment. Families were paid $50 for each assessment.
FEV1 was the primary outcome. Secondary outcomes were medication adherence, symptom severity and frequency, inpatient hospitalizations, and ED visits. Medication adherence was evaluated via the Family Asthma Management System Scale (FAMSS) and the Daily Phone Diary (DPD). Other outcomes were confirmed via medical records.
Patients in the FS control group received weekly home-based counseling for up to 6 months. Patients in the MST-HC treatment group were first engaged in a motivational session with a therapist and evaluated for asthma management with interviews and observations within the home and community. Once possible contributing factors to poor asthma management (such as medication underuse or low parental monitoring) were identified, targeted interventions such as skills training, behavioral and family therapy, or communication training with school and medical staff were chosen, and treatment goals continually monitored and modified, the authors said.
The mean length of treatment until termination in the MST-HC group was 5 months, and the mean number of sessions was 27. In the FS group, mean length of treatment was 4 months, and the mean number of sessions was 11.
FEV1 for the MST-HC group improved from 2.05 at baseline to 2.25 at 7 months (a 10% improvement), and to 2.37 (a 16% improvement) at 12 months, compared with an improvement from 2.21 to 2.31 at 7 months (a 4% improvement) and 2.33 (a 5% improvement) at 12 months in the control group, the authors reported.
At 12 months, FAMSS adherence scores improved from 4.19 to 5.24 in the MST-HC group and from 4.61 to 4.72 in the control group.
DPD adherence scores improved from a mean of 0.33 at baseline to 0.69 for the MST-HC group, and from 0.43 to 0.46 in the FS group.
At 12 months, the mean frequency of asthma symptoms in the MST-HC group improved from 2.75 at baseline to 1.43, compared with a decline of 2.67 to 2.58 in the control group. The mean number of hospitalizations in the MST-HC group improved from 0.87 to 0.24, compared with a change from 0.66 to 0.34 in the control group.
The study results are “especially noteworthy because African American adolescents experience greater morbidity and mortality from asthma than white adolescents even when controlling for socioeconomic variables,” Dr. Naar and her associates wrote. Future research should focus on the “transportability” of MST-HC treatment to community settings, which is “ready to be studied in effectiveness and implementation trials.”
The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate Multisystemic Therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
SOURCE: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
FROM PEDIATRICS
Key clinical point: Multisystemic Therapy–Health Care (MST-HC) significantly improved outcomes in African American adolescents with moderate to severe asthma.
Major finding: Patients randomly assigned to MST-HC treatment had greater improvement in FEV1 over time, compared with controls (beta = 0.097; t(164.27) = 2.52; P = .01).
Study details: A study of 167 African American patients aged 12-16 years, randomly assigned to either MST-HC or FS.
Disclosures: The study was supported by a National Institutes of Health grant. Coauthor Phillippe Cunningham, PhD, is a co-owner of Evidence-Based Services, a network partner organization that is licensed to disseminate multisystemic therapy for drug court and juvenile delinquency settings. The other authors said they have no potential conflicts of interest.
Source: Naar S et al. Pediatrics. 2018. doi: 10.1542/peds.2017-3737.
E-cigarette use highest among adults aged under 35 years
Almost 11 million adults use e-cigarettes in the United States, and the majority are under the age of 35 years, according to the American Heart Association.
As of 2016, an estimated 4.5% of adults – more than 10.8 million individuals – used e-cigarettes every day or some days, which defined current use for the 466,842 people who responded to the Behavioral Risk Factor Surveillance System survey and were included in the study conducted by the AHA’s Tobacco Regulation and Addiction Center and published in the Annals of Internal Medicine.
Based on that survey data, an estimated 51% of current users were under the age of 35 years in 2016. Daily use was highest among those aged 18-24 years, and of those respondents, 44% said that they had never been regular cigarette users. “It’s particularly disturbing to see these younger people who have never been regular cigarette smokers taking up the use of e-cigarettes, perhaps with the assumption that this alternative nicotine delivery system has been proven to be safe,” said Rose Marie Robertson, MD, who is the AHA’s chief science and medical officer.
The analysis also showed that about 60% of e-cigarette users were men and that use was higher among LGBT people. The first-ever estimates of current use by state put the prevalence highest in Oklahoma at 7.0% and lowest in South Dakota (3.1%) and the District of Columbia (2.3%), the AHA said.
The study was funded through a grant from the National Institutes of Health and the Food and Drug Administration’s Center for Tobacco Products.
rfranki@mdedge.com
SOURCE: Mirbolouk M et al. Ann Intern Med. 2018 Aug 28. doi: 10.7326/M17-3440.
Almost 11 million adults use e-cigarettes in the United States, and the majority are under the age of 35 years, according to the American Heart Association.
As of 2016, an estimated 4.5% of adults – more than 10.8 million individuals – used e-cigarettes every day or some days, which defined current use for the 466,842 people who responded to the Behavioral Risk Factor Surveillance System survey and were included in the study conducted by the AHA’s Tobacco Regulation and Addiction Center and published in the Annals of Internal Medicine.
Based on that survey data, an estimated 51% of current users were under the age of 35 years in 2016. Daily use was highest among those aged 18-24 years, and of those respondents, 44% said that they had never been regular cigarette users. “It’s particularly disturbing to see these younger people who have never been regular cigarette smokers taking up the use of e-cigarettes, perhaps with the assumption that this alternative nicotine delivery system has been proven to be safe,” said Rose Marie Robertson, MD, who is the AHA’s chief science and medical officer.
The analysis also showed that about 60% of e-cigarette users were men and that use was higher among LGBT people. The first-ever estimates of current use by state put the prevalence highest in Oklahoma at 7.0% and lowest in South Dakota (3.1%) and the District of Columbia (2.3%), the AHA said.
The study was funded through a grant from the National Institutes of Health and the Food and Drug Administration’s Center for Tobacco Products.
rfranki@mdedge.com
SOURCE: Mirbolouk M et al. Ann Intern Med. 2018 Aug 28. doi: 10.7326/M17-3440.
Almost 11 million adults use e-cigarettes in the United States, and the majority are under the age of 35 years, according to the American Heart Association.
As of 2016, an estimated 4.5% of adults – more than 10.8 million individuals – used e-cigarettes every day or some days, which defined current use for the 466,842 people who responded to the Behavioral Risk Factor Surveillance System survey and were included in the study conducted by the AHA’s Tobacco Regulation and Addiction Center and published in the Annals of Internal Medicine.
Based on that survey data, an estimated 51% of current users were under the age of 35 years in 2016. Daily use was highest among those aged 18-24 years, and of those respondents, 44% said that they had never been regular cigarette users. “It’s particularly disturbing to see these younger people who have never been regular cigarette smokers taking up the use of e-cigarettes, perhaps with the assumption that this alternative nicotine delivery system has been proven to be safe,” said Rose Marie Robertson, MD, who is the AHA’s chief science and medical officer.
The analysis also showed that about 60% of e-cigarette users were men and that use was higher among LGBT people. The first-ever estimates of current use by state put the prevalence highest in Oklahoma at 7.0% and lowest in South Dakota (3.1%) and the District of Columbia (2.3%), the AHA said.
The study was funded through a grant from the National Institutes of Health and the Food and Drug Administration’s Center for Tobacco Products.
rfranki@mdedge.com
SOURCE: Mirbolouk M et al. Ann Intern Med. 2018 Aug 28. doi: 10.7326/M17-3440.
FROM ANNALS OF INTERNAL MEDICINE
Obesity Extends Viral Shedding of Flu
Obesity not only makes flu more severe, but also lengthens the period of viral shedding for influenza A, according to a study by University of Michigan researchers, partly funded by the National Institute of Allergy and Infectious Diseases.
Over 3 flu seasons, the researchers monitored 1,783 people from 320 households in Managua, Nicaragua. During that time, 87 people became ill with influenza A and 58 with influenza B.
More than 40% of the adults aged > 18 years were obese, as defined by body mass. Obese adults with ≥ 2 symptoms of influenza A (n = 62) shed the virus 42% longer than did nonobese adults, or 5.2 days compared with 3.7 days, respectively. Obese adults with 1 or no symptoms of influenza A (n = 25) shed the virus 104% longer than nonobese adults—3.2 days compared with 1.6 days, respectively.
Obesity was not a risk factor for increased viral shedding duration in children aged 5 to 17 years or for adults with influenza B.
The researchers suggest that chronic inflammation caused by obesity may be responsible for the increased viral shedding. Reducing obesity rates could be an important target to limit the spread of viral infectious diseases, they suggest. The findings may have particular significance in the US, where in 2014 35% of adults were obese compared with 17.4% of adults in Nicaragua.
Obesity not only makes flu more severe, but also lengthens the period of viral shedding for influenza A, according to a study by University of Michigan researchers, partly funded by the National Institute of Allergy and Infectious Diseases.
Over 3 flu seasons, the researchers monitored 1,783 people from 320 households in Managua, Nicaragua. During that time, 87 people became ill with influenza A and 58 with influenza B.
More than 40% of the adults aged > 18 years were obese, as defined by body mass. Obese adults with ≥ 2 symptoms of influenza A (n = 62) shed the virus 42% longer than did nonobese adults, or 5.2 days compared with 3.7 days, respectively. Obese adults with 1 or no symptoms of influenza A (n = 25) shed the virus 104% longer than nonobese adults—3.2 days compared with 1.6 days, respectively.
Obesity was not a risk factor for increased viral shedding duration in children aged 5 to 17 years or for adults with influenza B.
The researchers suggest that chronic inflammation caused by obesity may be responsible for the increased viral shedding. Reducing obesity rates could be an important target to limit the spread of viral infectious diseases, they suggest. The findings may have particular significance in the US, where in 2014 35% of adults were obese compared with 17.4% of adults in Nicaragua.
Obesity not only makes flu more severe, but also lengthens the period of viral shedding for influenza A, according to a study by University of Michigan researchers, partly funded by the National Institute of Allergy and Infectious Diseases.
Over 3 flu seasons, the researchers monitored 1,783 people from 320 households in Managua, Nicaragua. During that time, 87 people became ill with influenza A and 58 with influenza B.
More than 40% of the adults aged > 18 years were obese, as defined by body mass. Obese adults with ≥ 2 symptoms of influenza A (n = 62) shed the virus 42% longer than did nonobese adults, or 5.2 days compared with 3.7 days, respectively. Obese adults with 1 or no symptoms of influenza A (n = 25) shed the virus 104% longer than nonobese adults—3.2 days compared with 1.6 days, respectively.
Obesity was not a risk factor for increased viral shedding duration in children aged 5 to 17 years or for adults with influenza B.
The researchers suggest that chronic inflammation caused by obesity may be responsible for the increased viral shedding. Reducing obesity rates could be an important target to limit the spread of viral infectious diseases, they suggest. The findings may have particular significance in the US, where in 2014 35% of adults were obese compared with 17.4% of adults in Nicaragua.
Adverse events outweigh promise of SGN-CD70A against NHL
An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.
Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.
However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.
Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.
SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.
Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.
The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.
Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.
The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.
Other common AEs were nausea and fatigue.
The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.
The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.
The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.
SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.
An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.
Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.
However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.
Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.
SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.
Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.
The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.
Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.
The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.
Other common AEs were nausea and fatigue.
The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.
The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.
The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.
SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.
An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.
Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.
However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.
Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.
SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.
Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.
The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.
Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.
The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.
Other common AEs were nausea and fatigue.
The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.
The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.
The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.
SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.
FROM INVESTIGATIONAL NEW DRUGS
Key clinical point: A high incidence of unexplained
Major finding: In total, 15 of 20 patients had treatment-related thrombocytopenias; 13 of these adverse events were grade 3 or greater in severity.
Study details: A 20-patient NHL cohort of a phase 1 dose-finding, pharmacologic, safety, and preliminary efficacy trial of the antibody-drug conjugate SGN-CD70A.
Disclosures: The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.
Source: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.
Breaking News: Trump Upends Federal Pay for 2019
In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.
The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."
In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more than 40,000 job openings.
"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero. These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.
President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.
In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.
The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."
In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more than 40,000 job openings.
"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero. These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.
President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.
In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.
The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."
In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more than 40,000 job openings.
"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero. These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.
President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.
New BTK inhibitor under review in China
for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.
The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.
Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.
for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.
The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.
Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.
for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.
The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.
Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.
Variation in bacterial drug susceptibility tied to TB relapse risk
Higher pretreatment drug concentrations close to a resistance breakpoint for susceptibility were associated with greater relapse risk in TB, based on data from 54 patients who relapsed and 63 who were treated and cured.
“We postulated that drug-susceptible Mycobacterium tuberculosis might have a graded spectrum of susceptibilities that could be used to determine the risk of relapse,” wrote Roberto Colangeli, PhD, of Rutgers University, Newark, N.J., and his colleagues.
In a study published in the New England Journal of Medicine, the researchers examined pretreatment bacterial isolates from adults with TB who had experienced relapse and those who were cured. Using these isolates, they identified the minimum inhibitory concentration (MIC) – the lowest concentration of the drug that prevents visible bacterial growth in culture – for isoniazid and rifampin.
Overall, after controlling for other potential relapse risk factors, higher pretreatment MIC values for both isoniazid and rifampin were associated with an increased relapse risk. For isoniazid, the average MIC below the breakpoint was 0.0334 mcg/mL for relapsed patients and 0.0286 mcg/mL for cured patients. For rifampin, the average MIC below the breakpoint was 0.0695 mcg/mL for relapsed patients and 0.0453 mcg/mL for cured patients. The higher values for the relapsed versus cured patients were represented by factors of 1.17 and 1.53 for isoniazid and rifampin, respectively.
The average age of the patients was 41 years; 83% were men, and 35% were non-Hispanic white.
The study findings were limited by several factors, including the small sample size, retrospective design, and inability to test MIC values from primary cultures versus subcultures, the researchers wrote. However, the results suggest an impact of MIC values on treatment outcomes, and “additional studies that are performed in larger, well-defined prospective cohorts and that include MIC testing of pretreatment culture isolates will be useful to better validate these findings,”
The study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Colangeli reported no financial conflicts. Dr. Alland disclosed funding from Cepheid and several current and pending patents in the United States and Europe, with some royalties paid to Cepheid.
SOURCE: Colangeli R et al. N Engl J Med. 2018;379:823-33.
Although standard four-drug therapy has been shown to cure 90% of patients in several clinical trials, patients do relapse for reasons such as poor treatment adherence and “variations in the characteristics of the infected patients or the infecting pathogens,” wrote Eric J. Rubin, MD, in an accompanying editorial (N Engl J Med. 2018;379:882-3).
Current antibiotic susceptibility thresholds are often set by committees using models, said Dr. Rubin. “Given the uncertainties in modeling, as has been seen in clinical studies, these breakpoints can be imperfect predictors of treatment response.”
Dr. Rubin proposed that minimum inhibitory concentration (MIC) concentrations could be an alternative to in vitro testing as a predictor of treatment response.
“The clinical laboratory provides us not only with a breakpoint interpretation but also with raw data, a quantitative assessment of MIC values,” he noted. “These values can be thought of more as probabilities of successful therapy than as absolute thresholds, a change in attitude that may dispel a false sense of security about the choice of regimen in the treatment of patients with tuberculosis.”
Dr. Rubin is affiliated with the department of immunology and infectious diseases at the Harvard School of Public Health, Boston. He had no relevant financial conflicts to disclose.
Although standard four-drug therapy has been shown to cure 90% of patients in several clinical trials, patients do relapse for reasons such as poor treatment adherence and “variations in the characteristics of the infected patients or the infecting pathogens,” wrote Eric J. Rubin, MD, in an accompanying editorial (N Engl J Med. 2018;379:882-3).
Current antibiotic susceptibility thresholds are often set by committees using models, said Dr. Rubin. “Given the uncertainties in modeling, as has been seen in clinical studies, these breakpoints can be imperfect predictors of treatment response.”
Dr. Rubin proposed that minimum inhibitory concentration (MIC) concentrations could be an alternative to in vitro testing as a predictor of treatment response.
“The clinical laboratory provides us not only with a breakpoint interpretation but also with raw data, a quantitative assessment of MIC values,” he noted. “These values can be thought of more as probabilities of successful therapy than as absolute thresholds, a change in attitude that may dispel a false sense of security about the choice of regimen in the treatment of patients with tuberculosis.”
Dr. Rubin is affiliated with the department of immunology and infectious diseases at the Harvard School of Public Health, Boston. He had no relevant financial conflicts to disclose.
Although standard four-drug therapy has been shown to cure 90% of patients in several clinical trials, patients do relapse for reasons such as poor treatment adherence and “variations in the characteristics of the infected patients or the infecting pathogens,” wrote Eric J. Rubin, MD, in an accompanying editorial (N Engl J Med. 2018;379:882-3).
Current antibiotic susceptibility thresholds are often set by committees using models, said Dr. Rubin. “Given the uncertainties in modeling, as has been seen in clinical studies, these breakpoints can be imperfect predictors of treatment response.”
Dr. Rubin proposed that minimum inhibitory concentration (MIC) concentrations could be an alternative to in vitro testing as a predictor of treatment response.
“The clinical laboratory provides us not only with a breakpoint interpretation but also with raw data, a quantitative assessment of MIC values,” he noted. “These values can be thought of more as probabilities of successful therapy than as absolute thresholds, a change in attitude that may dispel a false sense of security about the choice of regimen in the treatment of patients with tuberculosis.”
Dr. Rubin is affiliated with the department of immunology and infectious diseases at the Harvard School of Public Health, Boston. He had no relevant financial conflicts to disclose.
Higher pretreatment drug concentrations close to a resistance breakpoint for susceptibility were associated with greater relapse risk in TB, based on data from 54 patients who relapsed and 63 who were treated and cured.
“We postulated that drug-susceptible Mycobacterium tuberculosis might have a graded spectrum of susceptibilities that could be used to determine the risk of relapse,” wrote Roberto Colangeli, PhD, of Rutgers University, Newark, N.J., and his colleagues.
In a study published in the New England Journal of Medicine, the researchers examined pretreatment bacterial isolates from adults with TB who had experienced relapse and those who were cured. Using these isolates, they identified the minimum inhibitory concentration (MIC) – the lowest concentration of the drug that prevents visible bacterial growth in culture – for isoniazid and rifampin.
Overall, after controlling for other potential relapse risk factors, higher pretreatment MIC values for both isoniazid and rifampin were associated with an increased relapse risk. For isoniazid, the average MIC below the breakpoint was 0.0334 mcg/mL for relapsed patients and 0.0286 mcg/mL for cured patients. For rifampin, the average MIC below the breakpoint was 0.0695 mcg/mL for relapsed patients and 0.0453 mcg/mL for cured patients. The higher values for the relapsed versus cured patients were represented by factors of 1.17 and 1.53 for isoniazid and rifampin, respectively.
The average age of the patients was 41 years; 83% were men, and 35% were non-Hispanic white.
The study findings were limited by several factors, including the small sample size, retrospective design, and inability to test MIC values from primary cultures versus subcultures, the researchers wrote. However, the results suggest an impact of MIC values on treatment outcomes, and “additional studies that are performed in larger, well-defined prospective cohorts and that include MIC testing of pretreatment culture isolates will be useful to better validate these findings,”
The study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Colangeli reported no financial conflicts. Dr. Alland disclosed funding from Cepheid and several current and pending patents in the United States and Europe, with some royalties paid to Cepheid.
SOURCE: Colangeli R et al. N Engl J Med. 2018;379:823-33.
Higher pretreatment drug concentrations close to a resistance breakpoint for susceptibility were associated with greater relapse risk in TB, based on data from 54 patients who relapsed and 63 who were treated and cured.
“We postulated that drug-susceptible Mycobacterium tuberculosis might have a graded spectrum of susceptibilities that could be used to determine the risk of relapse,” wrote Roberto Colangeli, PhD, of Rutgers University, Newark, N.J., and his colleagues.
In a study published in the New England Journal of Medicine, the researchers examined pretreatment bacterial isolates from adults with TB who had experienced relapse and those who were cured. Using these isolates, they identified the minimum inhibitory concentration (MIC) – the lowest concentration of the drug that prevents visible bacterial growth in culture – for isoniazid and rifampin.
Overall, after controlling for other potential relapse risk factors, higher pretreatment MIC values for both isoniazid and rifampin were associated with an increased relapse risk. For isoniazid, the average MIC below the breakpoint was 0.0334 mcg/mL for relapsed patients and 0.0286 mcg/mL for cured patients. For rifampin, the average MIC below the breakpoint was 0.0695 mcg/mL for relapsed patients and 0.0453 mcg/mL for cured patients. The higher values for the relapsed versus cured patients were represented by factors of 1.17 and 1.53 for isoniazid and rifampin, respectively.
The average age of the patients was 41 years; 83% were men, and 35% were non-Hispanic white.
The study findings were limited by several factors, including the small sample size, retrospective design, and inability to test MIC values from primary cultures versus subcultures, the researchers wrote. However, the results suggest an impact of MIC values on treatment outcomes, and “additional studies that are performed in larger, well-defined prospective cohorts and that include MIC testing of pretreatment culture isolates will be useful to better validate these findings,”
The study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Colangeli reported no financial conflicts. Dr. Alland disclosed funding from Cepheid and several current and pending patents in the United States and Europe, with some royalties paid to Cepheid.
SOURCE: Colangeli R et al. N Engl J Med. 2018;379:823-33.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Risk of TB relapse increased with higher pretreatment minimum inhibitory concentration values for either isoniazid or rifampin.
Major finding: The higher values for the relapsed versus cured patients were represented by factors of 1.17 and 1.53 for isoniazid and rifampin, respectively.
Study details: The data come from a retrospective study of isolates from 54 patients with TB who relapsed and 63 who were treated and cured.
Disclosures: The study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Colangeli reported no financial conflicts. Dr. Alland disclosed funding from Cepheid and several current and pending patents in the United States and Europe, with some royalties paid to Cepheid.
Source: Colangeli R et al. N Engl J Med. 2018;379:823-33.