Department of Dermatology, University of Leipzig, Leipzig, Germany.
Department of Dermatology, University of Erlangen, Ulmenweg 18, D-91054, Erlangen, Germany.
Br J Dermatol. 2017 Nov;177(5):1299-1305. doi: 10.1111/bjd.15649. Epub 2017 Oct 29.
Current treatment of bullous pemphigoid (BP) is based on the long-term use of topical and/or systemic corticosteroids, which are associated with a high rate of adverse events and increased mortality.
To study the corticosteroid-sparing potential of azathioprine and dapsone.
This was a prospective, multicentre, randomized, nonblinded clinical trial that compared the efficacy and safety of two parallel groups of patients with BP treated with oral methylprednisolone 0·5 mg kg per day in combination with either azathioprine 1·5-2·5 mg kg per day or dapsone 1·5 mg kg per day. Nine German and Austrian departments of dermatology included 54 patients based on clinical lesions, positive direct immunofluorescence (IF) microscopy and detection of serum autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked immunosorbent assay. The primary end point was the time until complete tapering of methylprednisolone, and the most important secondary end point was the cumulative corticosteroid dose.
In eight patients (five azathioprine, three dapsone), methylprednisolone could be discontinued after a median time of 251 days in the azathioprine group and 81 days in the dapsone group. The median cumulative corticosteroid dose was 2·65 g for azathioprine compared with 1·92 g for dapsone (P = 0·06). The median numbers of days when corticosteroids were applied were 148 and 51, respectively (P = 0·24). No significant difference in the number of adverse events was seen between the treatment arms. Four patients (8%) died within the observation period of 12 months.
Due to the lower than intended number of patients, the results of the primary and secondary end points were not or only barely significant. Dapsone appeared to have a moderately higher corticosteroid-sparing potential than azathioprine. The combination regimen of either drug with oral methylprednisolone is associated with a relatively low 1-year mortality in this vulnerable patient population.
目前治疗大疱性类天疱疮（BP）的方法是长期使用局部和/或全身皮质类固醇，但其相关的不良反应发生率高，死亡率也有所增加。
研究硫唑嘌呤和氨苯砜的皮质类固醇节约潜力。
这是一项前瞻性、多中心、随机、非盲临床试验，比较了两组平行的 BP 患者的疗效和安全性，一组患者接受口服甲泼尼龙 0.5mg/kg/天联合硫唑嘌呤 1.5-2.5mg/kg/天治疗，另一组患者接受口服甲泼尼龙 0.5mg/kg/天联合氨苯砜 1.5mg/kg/天治疗。德国和奥地利的 9 个皮肤科部门根据临床病变、直接免疫荧光显微镜检查阳性和间接免疫荧光显微镜检查、免疫印迹或酶联免疫吸附试验检测到的血清自身抗体纳入了 54 例患者。主要终点是完全减少甲泼尼龙的时间，最重要的次要终点是累积皮质类固醇剂量。
在 8 例患者（5 例硫唑嘌呤，3 例氨苯砜）中，硫唑嘌呤组中位时间为 251 天，氨苯砜组为 81 天，可停用甲泼尼龙。硫唑嘌呤的累积皮质类固醇剂量中位数为 2.65g，氨苯砜为 1.92g（P=0.06）。应用皮质类固醇的天数中位数分别为 148 天和 51 天（P=0.24）。两组治疗中不良事件的数量没有显著差异。4 例患者（8%）在 12 个月的观察期内死亡。
由于患者数量低于预期，主要和次要终点的结果没有或只有轻微的统计学意义。氨苯砜似乎比硫唑嘌呤具有更高的皮质类固醇节约潜力。在这个脆弱的患者群体中，无论使用哪种药物联合口服甲泼尼龙，其联合方案的 1 年死亡率相对较低。
