Theophylline as 'add-on' therapy to cetirizine in patients with chronic idiopathic urticaria: A randomized, double-blind, placebo-controlled pilot study

Background: Chronic urticaria is a prevalent condition associated with substantial disability. Its pathogenesis is not clearly understood and is divided into autoimmune and chronic idiopathic urticaria (CIU). We investigated if the non-specific phosphodiesterase inhibitor theophylline could provide additional benefit to the histamine-1 receptor (H-1R) antagonist cetirizine in CIU. Methods: This was a double-blind, placebo-controlled, parallel study. Patients were randomized to receive either cetirizine and theophylline (200 mg twice daily; group A, 67 subjects) or cetirizine and placebo for 6 months (group B, 67 subjects). Group A patients took theophylline for 6 more months. Response was assessed by visual analog scale (VAS) and treatment effectiveness score (TES). Blood theophylline levels were also determined at visit t = 1 and t = 7. Results: The study was completed by 54 of the 67 patients (80.6%) in group A and 51 of the 67 patients (76.1%) in group B. The physician VAS values for group A were lower after t = 3, while the patient VAS values were decreased after t = 2. The physician and patient TES values in group A were statistically higher (p < 0.05) at all time points except for t = 1. At least 1 month of theophylline addition was necessary to obtain statistically significant benefit over cetirizine, and reducing theophylline by 50% during phase 2 did not alter this benefit. Pruritus values were reduced, but not statistically significant. Conclusions: Addition of theophylline to conventional H-1R antagonists was well tolerated without any adverse effects and provided considerable additional benefit in the management of CIU.