Search

We conducted a randomized, placebo-controlled, double-blind study to determine whether intranasal alpha 2-interferon could prevent respiratory illnesses in healthy contacts of ill family members. Beginning within 48 hours of the onset of illness in a family member, contacts self-administered interferon (5 X 10(6) IU) or placebo spray once daily for seven days. Respiratory illness developed during the eight-day period, starting with the second day of spraying, in 52 of 222 persons in the placebo group as compared with 32 of 226 in the interferon group (P = 0.02; efficacy, 39 percent). Among persons exposed to laboratory-documented rhinovirus colds, illness developed in 2 of 27 interferon recipients as compared with 12 of 34 placebo recipients (P = 0.02; efficacy, 79 percent). During the two-week period during and after spraying, rhinovirus colds developed in 1.3 percent of those spraying with interferon and in 15.1 percent of those spraying with placebo (P = 0.003; efficacy, 88 percent). Blood-tinged mucus or nasal mucosal bleeding or both were detected in 7.7 percent of placebo and 13.6 percent of interferon users (P = 0.04), but no evidence of cumulative nasal toxicity was found. We conclude that postexposure prophylaxis with intranasal interferon may in some cases provide an effective strategy for controlling the spread of natural colds, especially those caused by rhinoviruses.

Past studies conducted in Australian and American families have demonstrated that alpha 2b interferon (IFN) is effective in preventing rhinovirus-associated illnesses in exposed family members. IFN had been used by intranasal application for 7 days after exposure (5 x 10(6) IU/day). We used the same approach but with only 5 days of spraying (5 x 10(6) IU on day 1 and 2.5 x 10(6) IU on each subsequent day). This amount has been effective in studies involving seasonal prophylaxis. During the study period, a total of 178 rhinoviruses were isolated from the 199 enrolled families in Tecumseh, Mich. There were 434 courses of IFN use and 434 courses of placebo use. Although rhinoviruses were less frequently isolated from those using IFN than those using the placebo, no differences favoring IFN treatment could be found in any of the symptomatic episodes. In fact, more episodes were observed in IFN recipients than in placebo recipients, although the differences were not statistically significant. Additionally, there was no evidence of modification of the severity of episodes of illness. It was concluded that prevention of rhinovirus illness episodes postexposure required a dosage of at least 5 x 10(6) IU of IFN-alpha 2b.

Recombinant alpha-2b interferon was evaluated in two controlled trials, each lasting for 2 months or more, with different dose levels and schedules of administration. The first study was conducted during a period of transmission of type A (H1N1) and type B influenza. At 2.5 x 10(6) IU per day, no effect on influenza infection could be detected, but there appeared to be an effect on rhinovirus isolation. During the subsequent autumn 1.7 x 10(6) IU per day was found to have only a minimal effect on rhinovirus infection (efficacy from 22 to 27%). Under similar circumstances the preceding year, but with a daily dose of 3.0 x 10(6) IU, efficacy had been 76%. Since there was no evidence of change in rhinovirus strains circulating or their interferon susceptibility, this represented a dose-response relationship. It was possible to evaluate side effects in the 1,200 individuals involved. A lower dose was associated with lower frequency of symptoms of blood-tinged mucus. Persons using a placebo spray had a higher frequency of this side effect than an observed control. Using the spray 5 days a week was no less likely to produce symptoms than everyday use. Once-daily use was less likely to produce side effects than twice-daily use. There was no indication of sensitization when interferon was used for two separate periods of 4 weeks.

The safety, tolerance, and levels of drug in the nasal cavity produced by an ocular formulation of interferon were determined at four dosages in a placebo-controlled, double-masked trial. Interferon given by the ocular route was generally well tolerated, although a dose-related occurrence of subjective symptoms was detected.

In a double-blind evaluation of alpha 2-interferon as prophylaxis against naturally acquired respiratory infections, 120 adult members of 46 Australian families used 325 courses of intranasal spray during a six-month period, applying 5 million IU to the anterior nasal mucosa daily for seven days when respiratory symptoms developed in another member of the family. Used in this way, the alpha 2-interferon was well tolerated, and the rate of minor nasal bleeding (12 percent) did not increase with repeated courses. By comparison with the control group of 109 members of 49 families who used 319 seven-day courses of placebo spray, the users of alpha 2-interferon experienced 33 percent fewer days with nasal symptoms and 41 percent fewer episodes of "definite" respiratory illness. The users of alpha 2-interferon who were exposed to rhinovirus infections experienced 76 percent fewer days with symptoms and 86 percent fewer "definite" illnesses than their counterparts who used placebo. All of the observed clinical benefits, which suggested prevention of 6.8 "definite" respiratory illnesses per 100 courses of medication used, could be explained by a protective effect against illness associated with rhinoviruses that was not demonstrated for influenza A or B or coronavirus 229E.

In a double-blind, placebo-controlled study, patients with naturally occurring common colds of less than or equal to 48 h duration were randomly assigned to receive nasal sprays of recombinant alfa-2b interferon at 10 or 20 MU/day or placebo four times per day for 5 days. The 10-MU (n = 74), 20-MU (n = 74), and placebo (n = 72) groups had comparable frequencies of documented rhinovirus colds (50 to 65%) and mean durations of pretreatment symptoms (26 to 27 h). The median duration of colds tended to be longer in the 20-MU group (10 days) than the 10-MU group (8 days) or placebo group (8 days) (P = 0.06). In those with proven rhinovirus colds treated within 24 h, the median duration was significantly longer in the 20-MU group (9 days) than in the placebo group (6 days). No differences favoring interferon treatment were found in respiratory symptom scores or resolution of specific symptoms. On days 5 and 7, nasal washings from compliant subjects with proven rhinovirus colds yielded rhinoviruses more often in placebo (47 and 48%, respectively) than in interferon (15 and 16%, respectively) recipients (P less than 0.02), but no differences in new respiratory illness occurrence were observed in household contacts. Interferon recipients had significantly higher frequencies of blood in nasal mucus (16 to 18%) than did placebo recipients (4%) during treatment. Antibiotics for presumed secondary infections were given more often in the 20-MU group (11%) than in the placebo group (0%) (P less than 0.01). Nasal sprays of recombinant alfa-2b interferon were not an effective treatment for natural colds and were associated with toxicity.

Efficacy of intranasal recombinant alpha interferon (IFN-alpha 2b) was evaluated over a four-week period. The first 400 participants received either 1,500,000 IU of IFN-alpha 2b or placebo twice daily. Rhinovirus infections were prevented (protective efficacy, 76%). Parainfluenza infections were not prevented, but symptoms in associated episodes of disease were significantly reduced. The medication was generally well tolerated, but side effects were often observed. The most commonly reported symptom was blood-tinged mucus. A pilot study of IFN-alpha 2b or placebo administered on a once-daily dose schedule was also carried out in 150 participants. There was a suggestion of continued efficacy with reduced side effects. Overall, these findings would limit the use of IFN-alpha 2b on the twice-daily schedule to shorter time periods or to special situations in which the efficacy clearly outweighs side effects, and they encourage further examination of other dosage schedules.