건강한 성인에서 뉴라미니데이즈 억제제의 인플루엔자 치료 및 예방 : 종합 검토 및 메타 분석

[영국의학협회지(BMJ )] 2009년 12월 8일

뉴라미니데이즈 억제제(타미플루, 리렌자 등 인플루엔자 바이러스 치료제의 작용기전)에 대한 4개의 예방적 투여 및 12개의 치료적 투여에 관한 임상시험을 포함하는 20개의 임상시험에 관한 리뷰 및 메타 분석 논문입니다.

연구팀은 뉴라미니데이즈 억제제(타미플루, 리렌자 등)는 인플루엔자유사증상( influenza-like illness) 및 무증상 인플루엔자에 전혀 효과가 없는 것으로 나타났다고 결론을 내렸습니다.

인플루엔자 증상이 나타난 실험실 확정진단 환자에게서 경구용 오셀타미비르(oseltamivir, 타미플루)의 효능은  1일 투여용량 75 mg의 경우  61% ,  150 mg 의 경우 73%로 나타났습니다.

흡입용 자나미비르(zanamivir, 리렌자)의 효능은  1일 투여용량  10 mg 의 경우 62%로 나타났습니다.

항바이러스제 투여시 인플루엔자유사증상(ILE)를 경감시키는 시간은 타미플루(oseltamivir)가 1.20일, 리렌자(zanamivir)가 1.24일 정도인 것으로 나타났습니다. 다시 말해 인플루엔자 감염환자에게 타미플루나 리렌자를 투여할 경우, 약을 전혀 투여하지 않을 때보다 하루 정도 빨리 독감증상이 줄어든다고 볼 수 있습니다.

그리고 연구팀은 타미플루(oseltamivir)의 경우, 하부호흡기(하기도, lower respiratory tract )의 합병증을 줄여주지 못하는 것으로 보인다고 밝혔습니다.

따라서 결론적으로 뉴라미니데이즈 억제제(타미플루, 리렌자 등)는 건강한 성인에서 인플루엔자 증상을 소폭(완만하게) 개선시켜주는 효과가 있는 것으로 나타났습니다. 또한 뉴라미니데이즈 억제제(타미플루, 리렌자 등)는 인플루엔자 실험실 확정진단 후 투여할 경우 효과가 있지만, 인플루엔자유사증상( influenza-like illness) 및 무증상 인플루엔자에는 전혀 효과가 없는 것으로 나타났습니다.

그동안 비판적 전문가들은 건강한 성인들에게 예방적 목적으로 타미플루를 무분별하게 투여하는 것은 효과가 의심스럽고 돌연변이를 통한 내성 바이러스의 출현 등이 우려된다고 주장하며, 고위험군과 중증환자 등에 치료목적으로 제한적으로 투여하는 것이 바람직하다는 의견을 개진해왔습니다.

논문 전문은 첨부파일로 올려 놓았으며, 요약문은 아래와 같습니다.

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Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis (전문은 첨부파일 참조)

Tom Jefferson, researcher1, Mark Jones, statistician2, Peter Doshi, doctoral student3, Chris Del Mar, dean; coordinating editor of Cochrane Acute Respiratory Infections Group4

1 Acute Respiratory Infections Group, Cochrane Collaboration, Rome, Italy, 2 University of Queensland, School of Population Health, Brisbane, Australia, 3 Program in History, Anthropology, Science, Technology and Society, Massachusetts Institute of Technology, Cambridge, MA, USA, 4 Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia

Correspondence to: C Del Mar cdelmar@bond.edu.au

출처 : BMJ 2009;339:b5106, doi: 10.1136/bmj.b5106 (Published 8 December 2009)

Objectives To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects.
Search strategy An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts.

Selection criteria Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza.

Main outcome measures Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events.

Data extraction Two reviewers applied inclusion criteria, assessed trial quality, and extracted data.

Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose.

Results 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported.

Conclusion Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.

© Jefferson et al 2009
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