Ketotifen in the Prophylaxis of Extrinsic Bronchial Asthma: Efficacy
The intensity of asthmatic attacks during the day and night, as well as the total number of days with asthmatic attacks, decreased during treatment in both groups. At the end of treatment, there was a statistically significant difference between the two groups in favor of slow-release oral ketotifen. A Mann-Whitney rank-sum test with significance of p<0.01 was calculated on the frequency and intensity of asthmatic attacks during the day and night between weeks 6 and 12, as well as on the mean value of the results during weeks 8 to 12 (Fig 1). Clinical symptoms and signs (eg, cough, expectoration, nasal obstruction and discharge, runny eyes, cutaneous signs, and wheezing) also improved progressively. At the end of the trial treatment, analysis showed a statistically significant difference between the two groups for all symptoms except conjunctivitis and atopic eczema (Fig 2). There was a slight improvement in PEFR (Fig 3) and FEVt for both groups, but this was not statistically significant.
In 43 percent of the patients receiving the active drug, use of concomitant medication was reduced, compared to 27 percent of the patients receiving placebo (p<0.01). End-point analysis showed a statistically significant difference in favor of slow-release oral ketotifen in the use of (S-sympathomimetics and the number of days with P-sympathomimetic drug use between the two treatments (p<0.05) (Fig 4). Overall evaluation of efficacy at the end of treatment showed a statistically significant difference (p<0.01) between the two groups; patients categorized as “very good” and “good” comprised 76 percent of patients using slow-release oral ketotifen, compared to 30 percent in the placebo-treated group (Fig 5).
Side Effects, Compliance, and Tolerability
The most frequent side effects were “mild” and “moderate” sedation, sleepiness and drowsiness, which were reported in 44 percent of the patients receiving slow-release oral ketotifen (n = 130) and in 26 percent of the patients receiving placebo (n = 125). This difference was statistically significant (p<0.01). The side effects were mainly reported during the first two weeks (week 2) (in 42 percent of the patients receiving slow-release oral ketotifen and in 22 percent receiving placebo). In the succeeding eight weeks (weeks 4, 6, 8, and 10), sedation decreased from 42 percent to 11 percent and then to 5 percent in patients receiving slow-release oral ketotifen, compared with a decrease of 22 percent to 6 percent in patients receiving placebo. At the end of treatment (week 12), sedation was observed in 23 percent of the patients treated with slow-release oral ketotifen and in 13 percent of the patients receiving placebo (Fig 6). The percentage of patients not taking the prescribed trial drug was higher during the first (6 percent) and last (4 percent) two weeks of the trial (Table 3). This was determined from the pill count.
No significant differences in systolic and diastolic blood pressure and pulse rate were observed between the groups at any time during the trial. There were no clinically relevant drug-related changes in laboratory tests of hematopoietic, hepatic, or renal function associated with slow-release oral therapy with ketotifen.
Figure 1. Frequency of asthmatic attacks (numeric answers) during 12 weeks. End-point analysis (last CTRL) (mean values) showed statistically significant difference between two groups (Mann-Whitney rank-sum test, p<0.01).
Figure 2. Changes in clinical symptoms (cough and wheezing on auscultation). End-point analysis (average values for weeks 6 to 12) showed statistically significant difference between two groups (Mann-Whitney rank-sum test, p<0.01).
Figure 3. Changes of PEFR. No statistically significant difference between two groups was seen (Mann-Whitney rank-sum test).
Figure 4. Number of cases receiving 0-sympathomimetics (concomitant antiasthma medication) during 12 weeks of treatment. End-point analysis (last CTRL) (mean values) showed statistically significant difference between two groups (x2test, p<0.05).
Figure 5. Evaluation of efficacy by investigator at end of treatment showed statistically significant difference between two groups: ketotifen SRO (very good, and good, 76 percent) vs placebo (very good, and good, 30 percent).
Figure 6. Number of cases with sedation at control visit during 12 weeks. SRO, Slow-release oral.
Table 3—Percentage of NoncompUant Patients
|Croup||Noncompliant Patients, percent|
|Week 2||001<©||Week 10||Week 12|