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Clinical Inf. Dis.: Benefit of Early Oseltamivir Therapy for Adults Hospitalized with Influenza A: An Observational Study
#18,452
During the the opening months of the COVID pandemic we found ourselves facing a novel virus with few viable pharmaceutical options. Treatments were mainly supportive (ventilation, O2, IV fluids, etc.) along with a few desperate attempts to incorporate `off-label' drugs, many of which proved to be of limited value (see WHO Solidarity Therapeutics Trial: Remdesivir, HCQ, Lopinar/Ritonavir & Interferon Disappoint).
The first coronavirus vaccine wouldn't become widely available until early 2021, and the first experimental monoclonal antibody (Bamlanivimab) didn't receive a EUA until November 2020.
Unlike with COVID, should an influenza pandemic come along we do have a number of influenza specific antivirals, although none of them come close to being a `cure'. Most are most credited with shortening the duration and severity of an influenza infection (assuming they are started early enough in the infection).
The most widely used of these is oseltamivir (aka `Tamiflu'), which became the go-to drug nearly 20 years ago after resistance to the older drug Amantadine became insurmountable. There are others, including I.V. Peramavir and the newer Baloxavir, but oseltamivir is the most widely prescribed oral influenza antiviral.
A number of studies have questioned oseltamivir's value over the years, citing a paucity of `gold standard’ Randomized Control Trials (RCTs) demonstrating its effectiveness. Such studies, however, can be difficult to mount since it would be unethical to deny potentially life-saving antivirals to a `placebo group'.
Instead, we've had to rely on observational studies, many of which strongly suggest that antivirals - when given early - can reduce morbidity and mortality from influenza infection.
In December of 2012, in Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that appeared in the Journal of Infectious Diseases that spanned nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.
Their main finding was antiviral therapy - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.
And of interest with H5N1 threatening, in 2010’s Study: Antiviral Therapy For H5N1, a study of outcomes of H5N1 patients who either received, or did not receive, antiviral treatment found:
Out of 308 cases studied, the overall survival rate was a dismal 43.5%. But . . . of those who received at least one dose of Tamiflu . . . 60% survived . . . as opposed to only 24% who received no antivirals.
Admittedly, not a spectacular result, but most of these cases were only diagnosed and treated after several days of severe illness.
Despite these gaps in our knowledge, the CDC continues to encourage the early use of oseltamivir in high risk influenza patients, those with severe symptoms, or those who may be exposed to avian flu.
All of which brings us to a new study, published this week in Clinical Infectious Diseases, which reaffirms earlier studies showing the early administration of oseltamivir for influenza is associated with reduced severity and duration of infection.
Due to its length I've only reproduced the abstract and a snippet from the PDF. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study
Nathaniel M Lewis, PhD, Elizabeth J Harker, MPH, Lauren B Grant, MS, Yuwei Zhu, MD, MS, Carlos G Grijalva, MD, MPH, James D Chappell, MD, PhD, Jillian P Rhoads, PhD, Adrienne Baughman, Jonathan D Casey, MD, Paul W Blair, MD ... Show more
Clinical Infectious Diseases, ciae584, https://doi.org/10.1093/cid/ciae584
Published: 28 November 2024 Article history
Background
Methods
A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022–July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death.
Results
A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49–0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13–0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22–0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18–0.72).
In a 24-hospital network in the United States during the 2022–2023 influenza season, among adult patients hospitalized with influenza, early treatment with oseltamivir started on the same day as hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.
These findings support current recommendations, such as the IDSA Influenza Clinical Practice Guidelines and CDC guidance, to initiate oseltamivir treatment as soon as possible for adult patients hospitalized with influenza.
(Continue . . . )
While we would all prefer to have rock-solid, indisputable evidence based on well-mounted RCTs proving the effectiveness of Oseltamivir, the preponderance of evidence we have today indicates that NAIs can have a substantial positive therapeutic effect on influenza, particularly in high risk patients or with novel flu strains.
The real challenge with NAIs is getting them to patients in the first 24-48 hours of their illness.
Even during moderately severe seasonal flu epidemics we've seen spot shortages around the country (see 2022's CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir).
While there are plans to release oseltamivir from the national stockpile during an emergency, getting them that last mile from the pharmacy to the patient is always the toughest.
Which is why I hedge my bets by getting a flu shot every year. It never hurts to have a plan `B'.
https://afludiary.blogspot.com/2024/11/clinical-inf-dis-benefit-of-early.html
#18,452
During the the opening months of the COVID pandemic we found ourselves facing a novel virus with few viable pharmaceutical options. Treatments were mainly supportive (ventilation, O2, IV fluids, etc.) along with a few desperate attempts to incorporate `off-label' drugs, many of which proved to be of limited value (see WHO Solidarity Therapeutics Trial: Remdesivir, HCQ, Lopinar/Ritonavir & Interferon Disappoint).
The first coronavirus vaccine wouldn't become widely available until early 2021, and the first experimental monoclonal antibody (Bamlanivimab) didn't receive a EUA until November 2020.
Unlike with COVID, should an influenza pandemic come along we do have a number of influenza specific antivirals, although none of them come close to being a `cure'. Most are most credited with shortening the duration and severity of an influenza infection (assuming they are started early enough in the infection).
The most widely used of these is oseltamivir (aka `Tamiflu'), which became the go-to drug nearly 20 years ago after resistance to the older drug Amantadine became insurmountable. There are others, including I.V. Peramavir and the newer Baloxavir, but oseltamivir is the most widely prescribed oral influenza antiviral.
A number of studies have questioned oseltamivir's value over the years, citing a paucity of `gold standard’ Randomized Control Trials (RCTs) demonstrating its effectiveness. Such studies, however, can be difficult to mount since it would be unethical to deny potentially life-saving antivirals to a `placebo group'.
Instead, we've had to rely on observational studies, many of which strongly suggest that antivirals - when given early - can reduce morbidity and mortality from influenza infection.
In December of 2012, in Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that appeared in the Journal of Infectious Diseases that spanned nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.
Their main finding was antiviral therapy - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.
And of interest with H5N1 threatening, in 2010’s Study: Antiviral Therapy For H5N1, a study of outcomes of H5N1 patients who either received, or did not receive, antiviral treatment found:
Out of 308 cases studied, the overall survival rate was a dismal 43.5%. But . . . of those who received at least one dose of Tamiflu . . . 60% survived . . . as opposed to only 24% who received no antivirals.
Admittedly, not a spectacular result, but most of these cases were only diagnosed and treated after several days of severe illness.
Despite these gaps in our knowledge, the CDC continues to encourage the early use of oseltamivir in high risk influenza patients, those with severe symptoms, or those who may be exposed to avian flu.
CDC Study: Early flu Antiviral Treatment Can Shorten Hospital Stays in Children With Flu
CDC Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease).
CDC Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease).
All of which brings us to a new study, published this week in Clinical Infectious Diseases, which reaffirms earlier studies showing the early administration of oseltamivir for influenza is associated with reduced severity and duration of infection.
Due to its length I've only reproduced the abstract and a snippet from the PDF. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study
Nathaniel M Lewis, PhD, Elizabeth J Harker, MPH, Lauren B Grant, MS, Yuwei Zhu, MD, MS, Carlos G Grijalva, MD, MPH, James D Chappell, MD, PhD, Jillian P Rhoads, PhD, Adrienne Baughman, Jonathan D Casey, MD, Paul W Blair, MD ... Show more
Clinical Infectious Diseases, ciae584, https://doi.org/10.1093/cid/ciae584
Published: 28 November 2024 Article history
Background
clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza.
Methods
A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022–July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death.
Results
A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49–0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13–0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22–0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18–0.72).
Conclusion
Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.
(SNIP)Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.
In a 24-hospital network in the United States during the 2022–2023 influenza season, among adult patients hospitalized with influenza, early treatment with oseltamivir started on the same day as hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.
These findings support current recommendations, such as the IDSA Influenza Clinical Practice Guidelines and CDC guidance, to initiate oseltamivir treatment as soon as possible for adult patients hospitalized with influenza.
(Continue . . . )
While we would all prefer to have rock-solid, indisputable evidence based on well-mounted RCTs proving the effectiveness of Oseltamivir, the preponderance of evidence we have today indicates that NAIs can have a substantial positive therapeutic effect on influenza, particularly in high risk patients or with novel flu strains.
The real challenge with NAIs is getting them to patients in the first 24-48 hours of their illness.
Even during moderately severe seasonal flu epidemics we've seen spot shortages around the country (see 2022's CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir).
While there are plans to release oseltamivir from the national stockpile during an emergency, getting them that last mile from the pharmacy to the patient is always the toughest.
Which is why I hedge my bets by getting a flu shot every year. It never hurts to have a plan `B'.
https://afludiary.blogspot.com/2024/11/clinical-inf-dis-benefit-of-early.html
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