Sorbonne Université, Centre National de Référence Maladies Auoimmunes Systémiques Rares, Centre National de Référence Maladies Autoinflammatoires et Amylose Inflammatoire, INSERM 959, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
Groupe Hospitalier Pitié-Salpêtrière, AP-HP, and Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie, Paris, France.
Arthritis Rheumatol. 2019 Oct;71(10):1727-1732. doi: 10.1002/art.40912. Epub 2019 Aug 12.
Oral ulcers, the hallmark lesion of Behçet's disease (BD), can be disabling and resistant to conventional treatment, and there is a need for safe and effective treatment. We undertook this study to investigate the long-term safety and efficacy of ustekinumab therapy for BD-related oral ulcers that are resistant to colchicine.
This multicenter, prospective, open-label study included 30 patients who fulfilled the criteria of the International Study Group for BD and who were diagnosed as having active oral ulcers resistant to colchicine. Patients were treated subcutaneously with ustekinumab 90 mg at inclusion, at week 4, and then once every 12 weeks. Each patient was assessed longitudinally for the presence and number of oral ulcers, and median numbers of oral ulcers (with interquartile range [IQR]) were calculated. The primary efficacy end point was the proportion of patients at week 12 who experienced complete response, defined as having no oral ulcers.
The median number of oral ulcers per patient during ustekinumab therapy was significantly lower at week 12 compared to baseline (0 [IQR 0-1] versus 2 [IQR 2-3]; P < 0.0001). Complete response was achieved in 60.0% and 88.9% of patients at weeks 12 and 24, respectively. The median Behçet's Syndrome Activity Score (in which higher scores indicate more active disease) was significantly lower at weeks 12 and 24 (17.5 [IQR 10-42.5] and 10 [IQR 8-11], respectively) versus baseline (70 [IQR 50-70]; P < 0.0001). After a median follow-up of 12 months (IQR 6-16 months), 26 patients (86.7%) were still receiving ustekinumab treatment. Reasons for ustekinumab discontinuation included BD flare (n = 3) and side effects (n = 1). Seven patients (23.3%) experienced adverse events, including headaches (n = 4) and asthenia (n = 2), with no serious side effects.
Ustekinumab seems to be effective in treating BD-related oral ulcers that are resistant to treatment with colchicine.
口腔溃疡是贝赫切特病（BD）的标志性病变，可能导致残疾并对常规治疗产生耐药性，因此需要安全有效的治疗方法。我们进行这项研究旨在探讨乌司奴单抗治疗对秋水仙碱耐药的 BD 相关口腔溃疡的长期安全性和疗效。
这项多中心、前瞻性、开放标签研究纳入了 30 名符合国际 BD 研究组标准且诊断为秋水仙碱耐药性活动期口腔溃疡的患者。患者在纳入时、第 4 周和之后每 12 周皮下注射乌司奴单抗 90mg。对每位患者进行纵向评估，以评估口腔溃疡的存在和数量，并计算口腔溃疡的中位数（四分位距[IQR]）。主要疗效终点是第 12 周时完全缓解的患者比例，定义为无口腔溃疡。
与基线相比，乌司奴单抗治疗期间每位患者的口腔溃疡中位数在第 12 周时显著降低（0[IQR 0-1]比 2[IQR 2-3]；P<0.0001）。分别有 60.0%和 88.9%的患者在第 12 周和第 24 周时达到完全缓解。第 12 周和第 24 周时，贝赫切特病活动评分（评分越高表示疾病越活跃）中位数均显著低于基线（分别为 17.5[IQR 10-42.5]和 10[IQR 8-11]；P<0.0001）。中位随访 12 个月（IQR 6-16 个月）后，26 名患者（86.7%）仍在接受乌司奴单抗治疗。乌司奴单抗停药的原因包括 BD 发作（n=3）和不良反应（n=1）。7 名患者（23.3%）出现不良反应，包括头痛（n=4）和乏力（n=2），无严重不良反应。
乌司奴单抗似乎对秋水仙碱耐药的 BD 相关口腔溃疡有效。
