Ketotifen in the Prophylaxis of Extrinsic Bronchial Asthma: Conclusion
Although this procedure inescapably compounds differences based upon monitoring of symptoms (ie, drug usage is reduced until symptoms appear). Results of the present study show that 42 percent of the patients receiving slow-release oral ketotifen were able to reduce (or, in some cases, stop) the amount of additional antiasthmatic drug therapy, compared to 27 percent of patients receiving a placebo. This outcome accords with experience in previous trials with ketotifen, and the drug-sparing effect of ketotifen is comparable to that of cromolyn sodium in a study of similar design. read
An important problem in preventive drug treatment is long-term patient compliance. In asthma, this is adversely affected by a lack of subjectively perceived relief of symptoms that can be related directly to drug usage, duration of treatment, route of application, and the occurrence of side effects. The need for lengthy treatment, during which there may be a protracted interval without evident benefit, is well established in patients treated with ketotifen. Also, the need for one or two months of therapy before detection of benefit has emerged from numerous controlled studies. A five-year review of clinical trials by Craps and associates2 suggests that between 6 and 12 weeks of treatment may be mandatory for detection of a prophylactic effect. In this vein, it has been recommended that a trial of cromolyn sodium should preferably last one to two months before any decision is made regarding efficacy. It is likely that the patients compliance could have been influenced by the incidence of side effects, because during the first weeks, when the rate of side effects was high, overall noncompliance was also high. Nonetheless, the rate of noncompliance was relatively low in light of the high incidence of side effects during the period before treatment. This trend of reduced side effects and improved compliance was evident in both groups and may reflect adaptation to the questionnaire. Moreover, it is possible that sedative actions of slow-release oral ketotifen may diminish sleep disturbances so that this property is not necessarily perceived as an adverse effect by asthmatic patients.
In this trial, some of the clinical centers had patients in whom sedation was infrequent; in other centers, patients had a very high incidence of sedation. It is also interesting to note the high incidence of side effects (especially sedation, sleepiness and drowsiness) in the group receiving placebo (26 percent). The incidence of side effects arising from use of 2 mg of the slow-release oral formulation of ketotifen taken each night could be compared to that of a regimen of a 1 mg standard tablet of ketotifen taken twice per day. In earlier studies the incidence of side effects has been as high as 15 to 20 percent. The occurrence of increased side effects and increased noncompliance in both groups during weeks 10 to 12 reflects the outcome of reduction of concomitant therapy and indicates that this type of design may be inappropriate for the study of the efficacy of prophylactic drugs.
In conclusion, a slow-release oral formulation containing 2 mg of ketotifen administered once per day at night has been shown to be significantly more effective than a placebo in ameliorating the signs and symptoms of mild bronchial asthma over a treatment period of 12 weeks. Side effects (eg, sedation, sleepiness and drowsiness) occurred more frequently in the group receiving slow-release oral ketotifen than in the group receiving placebo, but this difference declined during continued treatment. The once-daily regimen of the new form of slow-release oral ketotifen seems to be superior to the twice-daily regimen in that the incidence of side effects was diminished without loss of efficacy, leading to improved compliance.