Oseltamivir: Do the recommendations reflect the evidence? ERIC KRUEGER, MD

Transcription

1 Oseltamivir: Do the recommendations reflect the evidence? ERIC KRUEGER, MD ADVOCATE LUTHERAN GENERAL HOSPITAL UNIVERSITY OF ILLINOIS - CHICAGO ACOEP SPRING SYMPOSIUM APRIL 3, 2018

2 Financial Disclosures 2 I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3 Objectives 3 Review the CDC recommendations for treatment of emergency department patients presenting with influenza and influenza-like illness Critically assess the clinical evidence used to support the current recommendations Evaluate the quality of the existing evidence for oseltamivir in treatment of influenza in emergency department patients

4 Learning points 4 Oseltamivir shortens the duration of symptoms in patients with influenza and probably has some mortality benefit in hospitalized patients but does not improve other patient oriented outcomes related to influenza Oseltamivir s effectiveness has been overexaggerated in the literature by publication bias Recommendations from the CDC regarding treatment of influenza do not accurately reflect the actual data that CDC used to make these recommendations nor do they take into account the best available data

5 Oseltamivir (Tamiflu) 5

6 Does it actually work? 6

7 Cochrane Oseltamivir Findings 7

8 Cochrane Oseltamivir Findings 8

9 MUltiparty Group for Advice on Science 9

10 MUltiparty Group for Advice on Science? 10

11 Cochrane MUGAS 11 Pneumonia: - Self-reported, unverified NNT Actual diagnosed no benefit - Children no benefit Pneumonia: - Lower respiratory infections getting abx NNT 26 Hospitalizations - No benefit Prophylaxis - NNT 33 - NNT (household) 7? Headache - NNH 32 Neuropsych (nervousness, depression, SI, confusion) - NNH 94? Decrease in pro-inflammatory cytokines and flu antibodies - Impacts ppx testing results Antipyretic effects 16.8/17.8h fewer symptoms Nausea NNH 28/26 Vomiting NNH 22/30 Hospitalizations - NNT 90 Neuropsych - No harm

12 Cochrane vs MUGAS 12

13 MUGAS 13

14 MUGAS 14

15 Cochrane MUGAS 15 Pneumonia: - Self-reported, unverified NNT Actual diagnosed no benefit - Children no benefit Pneumonia: - Lower respiratory infections getting abx NNT 26 Hospitalizations - No benefit Prophylaxis - NNT 33 - NNT (household) 7? Headache - NNH 32 Neuropsych (nervousness, depression, SI, confusion) - NNH 94? Decrease in pro-inflammatory cytokines and flu antibodies - Impacts ppx testing results Antipyretic effects 16.8/17.8h fewer symptoms Nausea NNH 28/26 Vomiting NNH 22/30 Hospitalizations - NNT 90 Neuropsych - No harm

16 Why does this matter so much in 2018? 16

17 Why does this matter so much in 2018? 17 Seasonal Influenza A(H3N2) Activity and Antiviral Treatment of Patients with Influenza

18 18

19 HAN Citation #1 19

20 HAN Citation #2 20

21 HAN Citation #3 21

22 HAN Citation #4 22

23 HAN Citation #5 23

24 HAN Citation #6 24 starting antiviral treatment more than 2 days after onset had survival benefit in adults versus no treatment.? With regard to neuraminidase inhibitor treatment started more than 2 days after symptom onset compared with none, we identified no significant association with mortality in all patients (adjusted OR 1 20 [95% CI ]), nor in laboratory confirmed cases, adults, pregnant women, or children.

25 HAN Citation #7 25 Also, a randomized, placebo-controlled study suggested clinical benefit when oseltamivir was initiated 72 hours after illness onset among febrile children with uncomplicated influenza.? When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups.

26 Exceptions! 26

27 So what did we learn? 27

28 So what did we learn? 28 CDC OSELTAMIVIR SCIENCE

29 29

30 References 30 Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet May 2;385(9979): doi: /S (14) Epub 2015 Jan 30. Doll MK, Winters N, Boikos C, Kraicer-Melamed H, Gore G, Quach C. Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: a systematic review of systematic reviews and/or meta-analyses. J Antimicrob Chemother Nov 1;72(11): Emergency Preparedness and Response. Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 27 Dec. 2017, emergency.cdc.gov/han/han00409.asp. Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Azim T, Bresee J, Luby SP, Brooks WA. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect Dis Feb;14(2): Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, Cheung A, Hovhannisyan G, Ivanova L, Flottorp SA, Saeterdal I, Wong AD, Uyeki TM, Akl EA, Alonso-Coello P, Smaill F, Schūnemann HJ. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, Spencer EA, Onakpoya I, Mahtani KR, Nunan D, Howick J, Heneghan CJ. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev Apr 10;(4):CD doi: / CD pub4. Malosh RE, Martin ET, Heikkinen T, Brooks WA, Whitley RJ, Monto AS. Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual Patient Data Meta-analysis of Randomized Controlled Trials. Clin Infect Dis Muthuri SG, PRIDE Consortium Investigators, Nguyen-Van-Tam JS.. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med May;2(5): Venkatesan S, Myles PR, Leonardi-Bee J, Muthuri SG, Al Masri M, Andrews N, Bantar C, Dubnoy-Raz G, Gérardin P, Koay ESC, Loh TP, Memish Z, Miller E, Oliva ME, Rath BA, Schweiger B, Tanq JW, Tran D, Vidmar T, Waight PA, Nguyen-Van-Tam JS. Impact of Outpatient Neuraminidase Inhibitor Treatment in Patients Infected With Influenza A(H1N1)pdm09 at High Risk of Hospitalization: An Individual Participant Data Metaanalysis. Clin Infect Dis May 15;64(10):