Pathania Yashdeep Singh, Bishnoi Anuradha, Parsad Davinder, Kumar Ashok, Kumaran Muthu Sendhil
Department of Dermatology, Venereology and Leprology, PGIMER, Sector 12, Chandigarh, 160012, India.
National Institute of Nursing Education, PGIMER, Sector 12, Chandigarh, 160012, India.
World Allergy Organ J. 2019 May 10;12(5):100033. doi: 10.1016/j.waojou.2019.100033. eCollection 2019.
Literature on the efficacy of azathioprine in antihistamine refractory chronic spontaneous urticaria (CSU) is limited.
To compare the efficacy and safety of azathioprine with respect to cyclosporine in the treatment of refractory CSU.
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.
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.
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.
关于硫唑嘌呤治疗抗组胺药难治性慢性自发性荨麻疹（CSU）疗效的文献有限。
比较硫唑嘌呤与环孢素治疗难治性CSU的疗效和安全性。
在这项前瞻性、随机、活性对照、非劣效性研究中，80例难治性CSU患者被给予环孢素（A组，n = 40）或硫唑嘌呤（B组，n = 40）治疗90天，并进一步随访90天。每15天使用荨麻疹活动评分（UAS7）和结果评分量表（OSS）评估治疗效果。在基线和第90天时还额外测量血清IgE水平、自体血清皮肤试验（ASST）和自体血浆皮肤试验（APST）。
A组31/40（79.5%）患者和B组32/40（80%）患者达到主要终点（第90天时UAS7降低≥75%）（比例差异-0.5%，差异的95%置信区间[CI]-17.13至18.09；点估计值支持B组，CI显示非劣效性）。在第180天时，A组19/40（47.95%）患者和B组24/40（60%）患者维持UAS7降低≥75%（比例差异-12.5%，差异的95%CI-9.00至32.46，点估计值支持B组，CI显示非劣效性）。因此，第180天时能够维持UAS7降低≥75%的患者数量在A组显著减少（比例差异30%，差异的95%CI 8.78至47.77），但在B组没有（比例差异20%，差异的95%CI-0.10至38.10）。A组和B组的平均UAS7值从基线时的28.70±4.42和28.88±4.25分别显著降至第90天时的5.56±5.12和7.0±4.48（A组，平均差异-23.27，差异的95%CI-25.33至-21.22；B组，平均差异-21.87，差异的95%CI-23.78至-19.96）。A组在第180天时显著升至9.98±5.46（平均差异4.55，差异的95%CI 2.98至6.12），但B组没有（第180天时平均UAS7 7.88±5.53，平均差异0.88，差异的95%CI-0.82至2.57）。治疗后ASST阳性患者数量的减少在A组显著，而IgE水平的降低在B组更显著。
本研究得出结论，硫唑嘌呤在治疗难治性CSU方面不劣于环孢素，并且它可以是一种有价值的辅助药物，特别是在资源匮乏的环境中。
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