Influenza cost-effectiveness of therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Cost-Effectiveness of Therapy Adapted from CDC [1][2]

Antiviral Drugs

  • Randomized, controlled trials conducted primarily among persons with mild illness in outpatient settings have demonstrated that zanamivir or oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day when administered within 48 hours of illness onset compared with placebo[3][4][5][6]
  • One randomized, controlled trial of oseltamivir treatment among 408 children aged 1--3 years reported that when oseltamivir was started within 24 hours of illness onset, the median time to illness resolution was shortened by 3.5 days compared with placebo.
  • Minimal or no benefit was reported in healthy children and adults when antiviral treatment was initiated more than 2 days after onset of uncomplicated influenza.
  • The amount of influenza viral shedding was reduced among those treated, but studies on whether the duration of viral shedding is reduced have been inconsistent [7][8][9][10][11] and the temporal and causal relationships between changes in influenza viral shedding and clinical outcomes have not been well-established.
  • One evidence review concluded that neuraminidase inhibitors were not effective in reducing the severity or duration of ILI (defined as acute respiratory infection with fever and cough).
  • However, a variety of pathogens can cause ILI besides influenza viruses, and this review did not conclude that neuraminidase inhibitors were ineffective in reducing laboratory-confirmed influenza among adults.[12]
  • Data are limited about the effectiveness of zanamivir and oseltamivir treatment in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases).
  • In a study that combined data from 10 clinical trials, the risk for pneumonia among those participants with laboratory-confirmed influenza receiving oseltamivir treatment was approximately 50% lower than among those persons receiving a placebo and 34% lower among patients at risk for complications (p is less than 0.05 for both comparisons).[13]
  • Although a similar significant reduction also was determined for hospital admissions among the overall group, the 50% reduction in hospitalizations reported in the small subset of high-risk participants was not statistically significant.[13]

One randomized, controlled trial found a decreased incidence of otitis media among children treated with oseltamivir. [6]

  • A randomized, controlled trial among children aged 1--3 years found an 85% reduction in acute otitis media when oseltamivir treatment was started within 12 hours of illness onset, but no reduction when treatment was started more than 24 hours from symptom onset.[14]
  • Another randomized, controlled study conducted among influenza virus-infected children with asthma reported greater improvement in lung function and fewer asthma exacerbations among oseltamivir-treated children compared with those who received placebo but did not determine a difference in symptom duration.[14]
  • Insufficient data exist regarding the effectiveness of any of the influenza antiviral drugs for use among children aged younger than 1 year.

Vaccination

  • A RCT conducted among 1,602 healthy children initially aged 15–71 months assessed the efficacy of trivalent LAIV against culture-confirmed influenza during two seasons.[15]
  • In season one, when vaccine and circulating virus strains were well-matched, efficacy in preventing laboratory-confirmed illness from influenza was 93% for participants who received two doses of LAIV.
  • In season two, when the A (H3N2) component was not well-matched between vaccine and circulating virus strains, efficacy was 86% overall.
  • A randomized, double-blind, placebo-controlled trial among 4,561 healthy working adults aged 18–64 years assessed multiple endpoints (i.e., targeted outcome measures), including reductions in self-reported respiratory tract illness without laboratory confirmation, absenteeism, health care visits, use of antibiotics, and use of over-the-counter medications for illness symptoms during peak and total influenza outbreak periods[16]). The study was conducted during the 1997-1998 influenza season, when the influenza vaccine and circulating A (H3N2) viruses were poorly matched. Vaccination was associated with reductions in severe febrile illnesses of 19%, and febrile upper respiratory tract illnesses of 24%.
  • Vaccination was also associated with fewer days of illness, fewer days of work lost, fewer days with health care provider visits, and reduced use of prescription antibiotics and over-the-counter medications. Among a subset of 3,637 healthy adults aged 18–49 years, LAIV recipients (n = 2,411) had 26% fewer febrile upper-respiratory illness episodes; 27% fewer lost work days as a result of febrile upper respiratory illness; and 18%–37% fewer days of health care provider visits caused by febrile illness, compared with placebo recipients (n = 1,226). Days of antibiotic use were reduced by 41%–45% in this age subset.
  • One study included 2,187 children aged 6–71 months who had recurrent respiratory tract infections[17] and found overall influenza rates of 2.3% among live vaccine recipients and 4.8% for TIV, for a 52.7% decrease in children receiving live vaccine compared to those receiving inactivated vaccine.
  • In a randomized study of 2,229 children aged 6–17 years with asthma, 4.1% of live vaccine recipients and 6.2% of TIV recipients developed influenza, for a relative reduction of 34.7%.[18]
  • Finally, in 2004-2005 a multinational RCT was conducted among 8,352 children aged 6–59 months. For the primary endpoint in this trial, culture-confirmed influenza-like illness, there were 45% fewer cases of influenza for well-matched influenza strains and 58% fewer for mismatched strains among live versus inactivated vaccine recipients.[19]

Chemoprophylaxis

  • In randomized, placebo-controlled trials, both oseltamivir and zanamivir were efficacious in the prevention of influenza illness among persons administered chemoprophylaxis after a household member or other close contact had laboratory-confirmed influenza (zanamivir: 72%--82%; oseltamivir: 68%--89%)[20][21][22][23][24][25]
  • Postexposure chemoprophylaxis with neuraminidase inhibitors generally should be reserved for those who have had recent close contact with a person with influenza.
  • Persons who can be considered for antiviral chemoprophylaxis include family or other close contacts of a person with a suspected or confirmed case who are at higher risk for influenza complications but have not been vaccinated against the influenza virus strains circulating at the time of exposure [26]
  • Unvaccinated health-care workers who have occupational exposures and who did not use adequate personal protective equipment at the time of exposure are also potential candidates for chemoprophylaxis [26].
  • Because of widespread resistance among currently circulating influenza A virus strains and inherent non-susceptibility among influenza B viruses, adamantanes have limited use in the prevention of influenza.
  • Persons who receive an antiviral medication for chemoprophylaxis might still acquire influenza virus infection and be potentially able to transmit influenza virus, even if clinical illness is prevented.[27][28]

References

  1. ↑ "CDC Flu Vaccine Effectiveness".
  2. ↑ "CDC Guidance on the Use of Influenza Antiviral Agents".
  3. ↑ Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG; et al. (1997). "Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group". N Engl J Med. 337 (13): 874–80. doi:10.1056/NEJM199709253371302. PMID 9302301.
  4. ↑ Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T; et al. (1999). "Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections". J Infect Dis. 180 (2): 254–61. doi:10.1086/314904. PMID 10395837.
  5. ↑ Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH; et al. (2000). "Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group". Lancet. 355 (9218): 1845–50. PMID 10866439.
  6. ↑ 6.0 6.1 Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D; et al. (2001). "Oral oseltamivir treatment of influenza in children". Pediatr Infect Dis J. 20 (2): 127–33. PMID 11224828.
  7. ↑ Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S; et al. (2008). "Time lines of infection and disease in human influenza: a review of volunteer challenge studies". Am J Epidemiol. 167 (7): 775–85. doi:10.1093/aje/kwm375. PMID 18230677.
  8. ↑ Cowling BJ, Chan KH, Fang VJ, Lau LL, So HC, Fung RO; et al. (2010). "Comparative epidemiology of pandemic and seasonal influenza A in households". N Engl J Med. 362 (23): 2175–84. doi:10.1056/NEJMoa0911530. PMC 4070281. PMID 20558368.
  9. ↑ Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE (1998). "Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense". J Clin Invest. 101 (3): 643–9. doi:10.1172/JCI1355. PMC 508608. PMID 9449698.
  10. ↑ Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M; et al. (1999). "Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment". JAMA. 282 (13): 1240–6. PMID 10517426.
  11. ↑ Sato M, Hosoya M, Kato K, Suzuki H (2005). "Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors". Pediatr Infect Dis J. 24 (10): 931–2. PMID 16220098.
  12. ↑ Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A (2006). "Antivirals for influenza in healthy adults: systematic review". Lancet. 367 (9507): 303–13. doi:10.1016/S0140-6736(06)67970-1. PMID 16443037. Review in: Evid Based Nurs. 2006 Oct;9(4):108 Review in: ACP J Club. 2006 Sep-Oct;145(2):45 Review in: Evid Based Med. 2006 Oct;11(5):141
  13. ↑ 13.0 13.1 Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F (2003). "Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations". Arch Intern Med. 163 (14): 1667–72. doi:10.1001/archinte.163.14.1667. PMID 12885681.
  14. ↑ 14.0 14.1 Heinonen S, Silvennoinen H, Lehtinen P, Vainionpää R, Vahlberg T, Ziegler T; et al. (2010). "Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial". Clin Infect Dis. 51 (8): 887–94. doi:10.1086/656408. PMID 20815736.
  15. ↑ Longini IM, Halloran ME, Nizam A, Wolff M, Mendelman PM, Fast PE; et al. (2000). "Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control". Vaccine. 18 (18): 1902–9. PMID 10699339.
  16. ↑ Nichol KL (1999). "Influenza vaccination for healthy working adults". Minn Med. 82 (11): 24–6. PMID 10589210.
  17. ↑ Ashkenazi S, Vertruyen A, Arístegui J, Esposito S, McKeith DD, Klemola T; et al. (2006). "Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections". Pediatr Infect Dis J. 25 (10): 870–9. doi:10.1097/01.inf.0000237829.66310.85. PMID 17006279.
  18. ↑ Fleming DM, Crovari P, Wahn U, Klemola T, Schlesinger Y, Langussis A; et al. (2006). "Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma". Pediatr Infect Dis J. 25 (10): 860–9. doi:10.1097/01.inf.0000237797.14283.cf. PMID 17006278.
  19. ↑ Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M; et al. (2007). "Live attenuated versus inactivated influenza vaccine in infants and young children". N Engl J Med. 356 (7): 685–96. doi:10.1056/NEJMoa065368. PMID 17301299.
  20. ↑ Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D; et al. (1999). "Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza". N Engl J Med. 341 (18): 1336–43. doi:10.1056/NEJM199910283411802. PMID 10536125.
  21. ↑ Hayden FG, Gubareva LV, Monto AS, Klein TC, Elliot MJ, Hammond JM; et al. (2000). "Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group". N Engl J Med. 343 (18): 1282–9. doi:10.1056/NEJM200011023431801. PMID 11058672.
  22. ↑ Eiland LS, Eiland EH (2007). "Zanamivir for the prevention of influenza in adults and children age 5 years and older". Ther Clin Risk Manag. 3 (3): 461–5. PMC 2386359. PMID 18488077.
  23. ↑ Welliver R, Monto AS, Carewicz O, Schatteman E, Hassman M, Hedrick J; et al. (2001). "Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial". JAMA. 285 (6): 748–54. PMID 11176912.
  24. ↑ Monto AS, Webster A, Keene O (1999). "Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis". J Antimicrob Chemother. 44 Suppl B: 23–9. PMID 10877459.
  25. ↑ Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM; et al. (2002). "Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households". J Infect Dis. 186 (11): 1582–8. doi:10.1086/345722. PMID 12447733.
  26. ↑ 26.0 26.1 "CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009--10 season. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/H1N1flu/recommendations.htm". External link in |title= (help); Missing or empty |url= (help)
  27. ↑ Lee, Vernon J; Yap, Jonathan; Tay, Joshua K; Barr, Ian; Gao, Qiuhan; Ho, Hanley J; Tan, Boon; Kelly, Paul M; Tambyah, Paul A; Kelso, Anne; Chen, Mark I (2010). "Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009". BMC Infectious Diseases. 10 (1): 164. doi:10.1186/1471-2334-10-164. ISSN 1471-2334.
  28. ↑ Khazeni N, Bravata DM, Holty JE, Uyeki TM, Stave CD, Gould MK (2009). "Systematic review: safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza". Ann Intern Med. 151 (7): 464–73. PMID 19652173. Review in: Ann Intern Med. 2010 Mar 16;152(6):JC3-3

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