The two most commonly used antiviral drugs for treating influenza infections, oseltamivir and zanamivir, each provide a net benefit to patients compared with no treatment, concluded the authors of a meta-analysis of 74 influenza antiviral observational studies published online Feb. 27 in Annals of Internal Medicine.
And in a separate report published in the same journal, another group of researchers found in a meta-analysis of 159 studies that evaluated rapid influenza diagnostic tests (RIDTs) that these tests have high specificity for positively identifying a patient infected with influenza but low sensitivity, which means that a negative test result cannot reliably rule out influenza infection (Ann. Intern. Med. 2012;156 [Epub ahead of print Feb. 28).
Both findings support existing U.S. recommendations from the Centers for Disease Control and Prevention (CDC) for the use of neuraminidase-inhibitor anti-influenza drugs and the use of RIDTs.
The antivirals meta-analysis, which was commissioned by the World Health Organization, included 51 observational studies that compared treatment with oral oseltamivir to no antiviral therapy. However, not every study looked at the same types of patients or the same outcomes, or had similar methods. For example, three studies assessed mortality rates in hospitalized patients and adjusted for age and comorbidities. This pooled analysis showed a statistically significant, 77% reduction in mortality compared with no antiviral therapy, suggesting that oral oseltamivir may reduce deaths, although the overall grade for the quality of the evidence was deemed low (Ann. Intern. Med. 2012;156 [Epub ahead of print Feb. 28, 2012]).
A second analysis included nine studies that also looked at the effect of oseltamivir on mortality in hospitalized patients, but these studies did not make any adjustments for possible confounders. The meta-analysis showed a more modest, 49% reduction in mortality.
Other parts of the oseltamivir analysis showed that its use reduced the rate of hospitalization among outpatients by 25%, and the duration of fever by approximately 33 hours. Oseltamivir use also reduced the incidence of neuropsychiatric events, as well as other signs and symptoms of influenza infection.
"Our findings indicate that the use of oral oseltamivir for treatment of influenza may provide net benefit by reducing mortality, the duration of symptoms, and complications of influenza. We observed a large, precise effect of oseltamivir on hospitalization" that was "compatible with the imprecise estimate from randomized controlled trials," wrote Dr. Holger J. Schünemann, chairman of the department of clinical epidemiology and biostatistics at McMaster University, Hamilton, Ont., and his associates.
The meta-analysis also included five observational studies and two surveys that compared the second marketed neuraminidase inhibitor, inhaled zanamivir, with no antiviral therapy in patients treated as outpatients. Two studies addressed hospitalization, and showed that patients with confirmed influenza or influenza-like illness who received zanamivir may be less likely to be hospitalized than patients who received no antiviral, a 34% reduction that was not statistically significant. Pooled results from three studies that reported on symptom duration showed an approximately 23-hour reduced duration of symptoms with zanamivir.
"Inhaled zanamivir reduces signs and symptoms, but we judged the overall confidence in the estimates of effect as very low, owing to imprecise and possibly biased data on mortality and hospitalization," the authors said. "A direct comparison between oral oseltamivir and inhaled zanamivir in eight studies showed that zanamivir may have a slight advantage in shortening the duration of signs and symptoms."
The meta-analysis also found that the evidence on the use of oral amantadine is "sparse, but may suggest a benefit from using this agent for treatment of drug-sensitive influenza A infection."
The analysis also suggested that earlier treatment with antivirals, within 48 hours, "may be of greater benefit" than later treatment.
"The potential positive effect of earlier rather than later administration of oseltamivir on death in hospitalized patients, and suggestions that pregnant women, children, and patients who are immunocompromised may also benefit from treatment, are among the key contributions of our study," the authors concluded. In addition, "we found moderate-quality evidence for the reduction in signs and symptoms from treatment with inhaled zanamivir compared with no treatment. The data suggest that oral oseltamivir could provide a net benefit in the treatment of patients with influenza, including a sizable reduction in hospitalized patients, although our confidence in these effects is low."
"Evidence that treatment with a neuraminidase inhibitor offers significant benefit in people with influenza is growing," commented Dr. Timothy R. Peters, a pediatric infectious diseases physician at Wake Forest University, Winston-Salem, N.C. As expected, those benefits are likely greatest in patients at highest risk for severe influenza disease, including pregnant women, young children, and immunocompromised patients. The findings of the meta-analysis generally support the recommendations of the CDC that encourage clinicians to aggressively protect influenza-infected patients at high risk for severe disease by using a neuraminidase inhibitor (MMWR 2011;60:1-24). Once the 2009 H1N1 pandemic ended, "it may be that clinicians do not prescribe neuraminidase inhibitors as aggressively as the CDC recommendations would support," he said.