BACKGROUND: Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of chronic urticaria. OBJECTIVE: A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with aleukotriene-modifying agent. METHODS:Patients 12 years or older with a history of chronic urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receivingcombination therapy versus monotherapy. RESULTS: Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 (P <.05 unless stated otherwise). Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6. Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5, physician recorded VAS at visits 4 and 5 and across visits 4 through 6, as well as for patient recorded VAS at visit 5. There were no significant results for patients with ASST negative results. CONCLUSION: The results of this study indicate that only patients with autoimmune (ASST positive) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with chronic urticaria with theASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria.
RCT Entities:
BACKGROUND: Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of chronic urticaria. OBJECTIVE: A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent. METHODS:Patients 12 years or older with a history of chronic urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy. RESULTS: Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 (P <.05 unless stated otherwise). Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6. Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5, physician recorded VAS at visits 4 and 5 and across visits 4 through 6, as well as for patient recorded VAS at visit 5. There were no significant results for patients with ASST negative results. CONCLUSION: The results of this study indicate that only patients with autoimmune (ASST positive) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with chronic urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria.