Guide
Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disorder typically characterized by spontaneous wheals and/or angioedema for more than 6 weeks, often accompanied by intense pruritus.
According to current consensus and guidelines, nonsedating second-generation H1 antihistamines (H1AH) are the first-line treatment for CSU, however, less than half of patients respond to standard doses of H1AH. For refractory patients, international guidelines recommend increasing the dose of H1AH. However, there are slight differences in the recommendations of different countries, such as the Japan guidelines: it can be replaced with other H1AH. Considering the significant increase in the adverse effects of doubling the dose, it is urgent to explore the best regimen for symptom control without affecting the quality of life of patients.
Bilastine is a non-sedating second-generation H1AH that has been approved in 90 countries for patients with urticaria and allergic rhinitis. Previous studies have shown that the use of bilastine is associated with better symptom control and a lower incidence of adverse effects early in treatment. Therefore, switching to bilastine may be an effective alternative for the treatment of patients with refractory CSU. Recently, data from a phase IV, multicenter, open-label, randomized, parallel-group comparative study were published, showing that for patients with refractory CSU, switching to a standard dose of birasten is not inferior to using a double dose of H1AH, and has a good safety profile.
About the study
This multicenter study was conducted in Japan to evaluate the efficacy and safety of switching to standard-dose birasten treatment versus 2-dose H1AH in patients with refractory CSU.
Adults over 20 years of age with a clinical diagnosis of refractory CSU (treated with regular-dose second-generation non-sedative or mildly sedative antihistamines for more than one week, persistent pruritus or wheals, and urticaria control score [UCT] ≤11) were included. Patients with urticaria with obvious triggers, patients with chronic itching (eczema, contact dermatitis, and atopic dermatitis) other than CSU, antihistamine allergy, patients who have used hormones or immunosuppressants within the past 4 weeks or received first-generation antihistamines, H2 receptor antagonists, or antileukotriene drugs within 1 week, patients who have been treated with omalizumab in the past, pregnant or lactating women, etc.
Subjects were randomly assigned 1:1 to bilastine (20 mg orally once daily) or double-dose H1AH (twice daily oral) for 7 days of follow-up, and subgroup analyses were performed according to UCT < score of 8 or ≥8.
The primary endpoint was the mean of the total symptom score (TSS) on days 5-7. Secondary endpoints include changes in the Japan version of the Epworth Sleepiness Scale (JESS) and urticaria activity score (UAS7), dermatology life quality index (DLQI), and TSS score after the intervention. An adverse event is defined as any illness, disability, death, or infection that occurs during the study. Adverse events and adverse drug reactions were recorded to assess safety endpoints.
Findings:
A total of 128 patients were included in this study (n=64 in the bilastine group; n=64 in the 2-fold H1AH group).
Primary endpoint
On days 5-7 post-dose, the difference in TSS between the bilastine group and the double-dose H1AH group was 0.17 (95% CI -0.32, 0.67), which was less than the non-inferiority cut-off of 0.8, indicating that the efficacy of the bilastine group was not inferior to that of the double-dose H1AH group. When stratified according to UCT (<8 and ≥8), the difference in TSS between groups with high UCT was 0.01 (95% CI -0.62, 0.64) compared to 0.03 (95% CI -0.43, 1.02) in patients with low UCT (Figure 1, Table 1). This suggests that doubling the dose of H1AH may be beneficial compared to switching to bilastine in poorly controlled patients.
Figure 1: Forest plot of TSS difference between the bilastine group and the double-dose H1AH group MD: mean difference; CI: confidence interval; Dotted line: Non-inferiority
Table 1: Differences in primary and secondary endpoints between groups
Secondary endpoints
After 1 week of treatment, the between-group difference in JESS changes was -0.07 (95% CI -1.26, 1.11), suggesting that the effect of drowsiness was comparable to that of the two-dose H1AH group in the bilastine group. When stratified according to UCT (<8 and ≥8), it was found that when UCT ≥8, the difference between groups was -1.36 (95% CI -3.26, 0.54) (Table 1), suggesting that patients with reasonable control had fewer adverse effects of switching to Rastine sleepiness.
In addition, the difference between UAS7 groups was 0.07 (95% CI -2.91, 3.05; p=0.5181), the difference in DLQI was 0.02 (95% CI -1.29, 1.30; p=0.9794) (Table 1), indicating that the efficacy of the bilastine group was not inferior to that of the double-dose H1AH group in the evaluation of other indicators.
security
During the study, there were no serious adverse events in either group.
Occurrence of adverse events: 5 (7.8%) in the double-dose H1AH group and 3 (4.7%) in the bilastine group. Among the comparisons of H1AH-related adverse events (drowsiness, malaise, dry mouth, headache, and dizziness), there were 5 in the double-dose H1AH group and 2 in the bilastine group (Table 2).
Table 2: Adverse events observed in both groups
Conclusions of the study
比拉斯汀可作为难治性CSU患者的治疗选择，尽管该研究是在少数患者中进行，且随访时间相对较短，但结果仍表明：比拉斯汀（20mg）治疗难治性CSU患者，与双倍剂量H1AH相比，具有相同的疗效和安全性。 需要进一步的研究来评估长期临床结局。 参考文献：Fukunaga A, Kakei Y, Murakami S, et al. Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study[J]. Front Immunol, 2024,15:1441478.