Comparing azathioprine with cyclosporine in the treatment of antihistamine refractory chronic spontaneous urticaria: A randomized prospective active-controlled non-inferiority study.

Background: Literature on the efficacy of azathioprine in antihistamine refractory chronic spontaneous urticaria (CSU) is limited.

Objective: To compare the efficacy and safety of azathioprine with respect to cyclosporine in the treatment of refractory CSU.

Methods: In this prospective, randomized, active-controlled, non-inferiority study, 80 patients of refractory CSU were administered either cyclosporine (group A, n ​= ​40) or azathioprine (group B, n ​= ​40) for 90 days and followed up for further 90 days. The treatment efficacy was assessed every 15th day using urticaria activity score (UAS7) and outcome scoring scale (OSS). Serum IgE levels, autologous serum skin test (ASST) and autologous plasma skin test (APST) were additionally measured at baseline and 90th day.

Results: Primary end point (≥75% reduction in UAS7 at 90th day) was achieved by 31/40 (79.5%) patients in group A and 32/40 (80%) patients in group B (proportion difference -0.5%, 95% confidence interval [CI] of difference -17.13 to 18.09; point estimates favoring B, CIs demonstrating non-inferiority). At 180th day, ≥75% reduction in UAS7 was maintained in 19/40 (47.95%) patients in group A and 24/40 (60%) patients in group B (proportion difference -12.5%, 95% CI of difference -9.00 to 32.46, point estimates favoring B, CIs demonstrating non-inferiority). Thus, the number of patients who could maintain ≥75% reduction in UAS7 at 180th day reduced significantly in group A (proportion difference 30%, 95% CI of difference 8.78 to 47.77), but not in group B (proportion difference 20%, 95% CI of difference -0.10 to 38.10). The values of mean UAS7 significantly decreased from 28.70 ​± ​4.42 and 28.88 ​± ​4.25 at baseline, to 5.56 ​± ​5.12 and 7.0 ​± ​4.48 at 90th day in group A and B respectively (group A, mean difference -23.27, 95% CI of difference -25.33 to -21.22; group B, mean difference -21.87, 95% CI of difference -23.78 to -19.96). It increased significantly to 9.98 ​± ​5.46 in group A at 180th day (mean difference 4.55, 95% CI of difference 2.98 to 6.12), but not in group B (mean UAS7 180th day 7.88 ​± ​5.53, mean difference 0.88, 95% CI of difference -0.82 to 2.57). The reduction in number of patients having positive ASST post-treatment was significant in group A, whereas reduction in IgE levels was more significant in group B.

Conclusion: The present study concludes that azathioprine is not inferior to cyclosporine in the treatment of refractory CSU, and it can be a valuable adjunct, especially in resource poor settings.