http://www.cdc.go.kr/CDC/info/CdcKrInfo0301.jsp?menuIds=HOME001-MNU0004-MNU0036-MNU0037&q_type=B&q_value=2012&cid=18416&pageNum=4

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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Experts: Overuse of flu drugs could cut effectiveness
Experts: Most “worried well” who were exposed to flu but not sick should not get antiviral drugs

By Bob LaMendola South Florida Sun Sentinel

출처 : South Florida Sun-Sentinel 5:01 p.m. EDT, September 15, 2009
http://www.sun-sentinel.com/business/sfl-swine-flu-preparation-091609,0,5300569.story

Doctors and hospitals should prepare not only for a surge of swine flu patients but also the “worried well,” relatives and friends who may accompany them asking for treatment because they were exposed to the virus, a panel of South Florida experts said Tuesday.

Only high-risk people such as the chronically ill should be given antiviral drugs solely to prevent an infection after they were exposed to a sick person, and medical professionals will have to be strong in saying no to the rest of the “worried well,” panel members said during a swine flu seminar at Broward General Medical Center in Fort Lauderdale.

“You will have a lot of panicky, demanding family members in your office. How do you deal with that? It’s up to your intestinal fortitude,” said Dr. Stephen Renae, an infectious disease specialist.

Antiviral drugs like Tamiflu and Relenza can shorten the duration of swine flu and can prevent it from causing illness in those who are exposed to the H1N1 flu virus, if taken within about 48 hours of the start of symptoms.

But the flu has been fairly mild so far, and the Centers for Disease Control and Prevention does not recommend giving drugs as a preventive measure except in those for whom the flu is a big risk, including pregnant women, children, adolescents and people with chronic illnesses such as lung disease, heart diseases and the like.

Also, a few cases of Tamiflu-resistant swine flu have appeared, making flu experts worry that overuse of antiviral drugs may reduce their effectiveness in stopping the flu in sick people. It’s also impotant to be sure sufficient supplies of antiviral drugs are available to those who need them, experts say. Doctors facing healthy, low-risk people who want drugs as a preventive should try to explain the situation, the panel said.

“Doctors need to use their best judgment and follow the CDC rules,” said Dr. Paula Thaqi, director of the Broward County Health Department. The same will be true, she said, when the first batches of H1N1 vaccine comes out in a few weeks and will be reserved for high-risk groups.

Dawn Nesbitt, chief emergency room nurse at Plantation General Hospital, who attended the seminar, said entire families have come to the ER asking about Tamiflu when a child in the household gets sick.

Eight to 10 sick students per day have been coming to her ER, sent there by schools when family members cannot get free to pick them up and bring them home, Nesbitt said.

The Palm Beach County Health Department has been trying to head off big crowds of people flooding physician offices and ERs by urging people to take care of themselves at home unless their symptoms are worrisome.

“You don’t necessarily have to run to the doctor’s office. Do that good old self-care, just like folks have done with influenza in the past,” said Al Grasso, coordinator for emergency preparation at the department.

Overall, Thaqi said she is pleased with the level of flu planning by doctors, hospitals and emergency rescue staffers in the community. Grasso said the same.

The new H1N1 virus is a worry for health experts because of its potential, not because it’s a major danger now. When it first came out in April, doctors feared it would be highly virulent and kill thousands. So far, it hasn’t. The nation has seen about 600 deaths, Florida 78. Experts still worry that the virus could mutate and become more serious, but so far that hasn’t happened.

“We’re hoping that will be a busy flu season and that’s all,” said Dr. Nabil El Sanadi, emergency medicine chief at the tax-assisted Broward Health system.

Bob LaMendola can be reached at blamendola@SunSentinel.com or 954-356-4526 or 561-243-6600, ext. 4526