An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone
An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone
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DOI：
10.1111/bjd.15649
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发表时间：
2017-11-01
影响因子：
10.3
通讯作者：
Schmidt, E.
中科院分区：
文献类型：
--
作者：
Sticherling, M.;Franke, A.;Schmidt, E.
背景目前大疱性类天疱疮（BP）的治疗是基于长期使用局部和/或全身皮质类固醇，这与高不良事件发生率和死亡率增加有关。目的研究硫唑嘌呤和氨苯砜的皮质类固醇节省潜力。方法本研究为前瞻性、多中心、随机、非盲临床试验，比较两组患者口服甲泼尼龙0.5 mg kg·1/d联合硫唑嘌呤1.5-2.5 mg kg·1/d或氨苯砜1.5 mg kg·1/d的疗效和安全性。9个德国和奥地利皮肤科包括54例患者的临床病变，阳性直接免疫荧光（IF）显微镜和血清自身抗体检测间接IF显微镜，免疫印迹或酶联免疫吸附试验。主要终点是甲基强的松龙完全减量的时间，最重要的次要终点是皮质类固醇累积剂量。结果8例患者（硫唑嘌呤组5例，氨苯砜组3例）中，甲基强的松龙可在硫唑嘌呤组251天和氨苯砜组81天后停用。硫唑嘌呤的中位累积皮质类固醇剂量为2.65 g，而氨苯砜为1.92 g（P = 0.06）。应用皮质类固醇的中位天数分别为148天和51天（P = 0.24）。两治疗组之间的不良事件数量无显著差异。4例患者（8%）在12个月的观察期内死亡。结论：由于患者数量低于预期，主要和次要终点的结果不显著或仅勉强显著。氨苯砜似乎比硫唑嘌呤具有中等程度的皮质类固醇节省潜力。任何一种药物与口服甲基强的松龙的联合方案与该脆弱患者人群相对较低的1年死亡率相关。
Background Current treatment of bullous pemphigoid (BP) is based on the longterm use of topical and/or systemic corticosteroids, which are associated with a high rate of adverse events and increased mortality. Objectives To study the corticosteroid-sparing potential of azathioprine and dapsone. Methods 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.1 per day in combination with either azathioprine 1.5-2.5 mg kg.1 per day or dapsone 1.5 mg kg.1 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. Results 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. Conclusions 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.