Date Published: July 06, 2013
Publisher: Blackwell Publishing Ltd
Author(s): K Krause, A Spohr, T Zuberbier, M K Church, M Maurer, Werner Aberer.
Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.
Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine.
Bilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1–3 h after cold challenge were significantly (P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treat-ment was well tolerated without evidence of increased sedation with dose escala-tion. Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines.
This was a prospective, randomized, double-blind, placebo-controlled, triple cross-over study to assess the efficacy, mechanisms and safety of treatment with 20 mg, 40 mg, 80 mg of bilastine and placebo administered once daily for 7 days in patients with cold contact urticaria. The design of the study is shown in Fig. 1. A total of 20 patients (seven men and 13 women, mean age 45 years, range 22–68 years) with a confirmed diagnosis of CCU made at least 6 weeks before screening were included in this study. The group size was estimated using a power of 80% (t-test) with a two-sided significance level of 5% and a medium effect of 1.2 SD. The patients were drawn from the outpatient population at the urticaria specialty clinic of the Allergie-Centrum-Charité-Universitätsmedizin and associated dermatological institutions in Berlin, Germany.
This study showed that bilastine given daily for seven days before provocation is an effective H1-antihistamine in reducing the symptoms of cold contact urticaria, including wheal formation and pruritus. Increasing the dose of bilastine from 20 mg through 40 mg to 80 mg daily increased its effectiveness. Sedation was reported by only one patient with 40 mg bilastine. Histamine release was unaffected during the early phase of the response (0–20 min). However, levels of histamine collected during the 20- to 60-min period and IL-6 and IL-8 collected during the 2- to 3-hour period were significantly reduced, particularly when patients were treated with bilastine 80 mg.