Dermatologic and Ocular Diseases
The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results

https://doi.org/10.1016/j.jaci.2003.10.002Get rights and content

Abstract

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 H1-antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcϵRI 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 H1-antagonist monotherapy might benefit from the addition of the leukotriene D4–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.

Section snippets

Subjects

Patients with chronic urticaria were recruited from 7 centers. Enrollment criteria required that patients be 12 years of age or older, have a history of urticaria for at least 6 weeks' duration, and have at least 6 hives present 2 days per week. Only subjects with a history of a suboptimal response to H1 antagonists were recruited. Therefore, a treatment effectiveness score (TES) of less than 5 while taking an H1 antagonist (on a scale of 0 to 10) was required at the time of enrollment.

Study design

Fig 1

Results

Table I summarizes the demographic characteristics of the population studied and displays the baseline (post-randomization) TES and VAS scores. There were no statistically significant differences between the groups. A total of 95 patients were enrolled with 86 completing the study. Numbers of patients at visits 4, 5, and 6 were 95, 90, and 86, respectively. There were 3 and 6 patients in the combination and monotherapy groups, respectively, who did not complete the study. Those who dropped from

Discussion

Leukotrienes have been identified as potentially important bioactive mediators that participate in the pathogenesis of chronic urticaria.24 The purpose of this study was to determine whether blocking LTD4 receptors with a leukotriene receptor antagonist (zafirlukast) in combination with an H1 antagonist was more effective than an H1 antagonist alone in the treatment of refractory chronic urticaria. We found that patients with chronic urticaria exhibiting an incomplete response to H1-antagonist

Acknowledgments

Investigator sites included Hal Nelson, Anjuli Nayak, Theodore Chu, Sheldon Spector, Jonathan Corren, and Albert Finn.

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