2019年11月14日出版的《新英格兰医学杂志》发表了土耳其伊斯坦布尔大学Gülen Hatemi研究团队的最新成果，他们的研究探讨了阿普司特治疗白塞病相关口腔溃疡的疗效和安全性。

小分子磷酸二酯酶-4抑制剂阿普司特可调节白塞病中上调的细胞因子。在此前的白塞病患者临床2期试验中，阿普司特降低了口腔溃疡的发生率和严重程度。但对于活动性口腔溃疡且之前未接受过生物制剂的白塞病患者，阿普司特治疗的有效性和安全性数据仍有限。

在这项临床3期试验中，研究组招募了207名患有活动性口腔溃疡且无主要器官受累的白塞病患者，按1：1随机分组，其中104名接受口服30mg阿普司特治疗，103名接受口服安慰剂，每日两次，为期12周，之后再随访52周。采用曲线下面积（AUC）对口腔溃疡总数进行评估，数值越小表明溃疡越少。采用白塞病生活质量评分对患者的生活质量进行评估，0-30，分数越高，生活质量越差。

治疗12周，阿普司特组的口腔溃疡数AUC为129.5，显著小于安慰剂组的222.1。阿普司特组的白塞病生活质量得分较基线下降了4.3分，安慰剂组则下降了1.2分。阿普司特的不良反应主要包括腹泻、恶心和头痛。

总之，阿普司特治疗白塞病相关的口腔溃疡患者，与安慰剂相比，可显著减少口腔溃疡数量，但容易发生腹泻、恶心和头痛等不良反应。

附：英文原文

Title: Trial of Apremilast for Oral Ulcers in Behet’s Syndrome

Author: Gülen Hatemi, M.D.,, Alfred Mahr, M.D., M.P.H., Ph.D.,, Yoshiaki Ishigatsubo, M.D., Ph.D.,, Yeong-Wook Song, M.D.,, Mitsuhiro Takeno, M.D., Ph.D.,, Doyoung Kim, M.D., Ph.D.,, Melike Melikolu, M.D.,, Sue Cheng, M.D., Ph.D.,, Shannon McCue, Ph.D.,, Maria Paris, M.D.,, Mindy Chen, M.S.,, and Yusuf Yazici, M.D.

Issue&Volume: 2019-11-13

Abstract:

Background

The small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behet’s syndrome. In a phase 2 trial involving patients with Behet’s syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behet’s syndrome who had active oral ulcers and had not previously received biologic agents are limited.

Methods

In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behet’s syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behet’s Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed.

Results

A total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, 92.6; 95% confidence interval [CI], 130.6 to 54.6; P<0.001). The change from baseline in the Behet’s Disease Quality of Life score was 4.3 points in the apremilast group, as compared with 1.2 points in the placebo group (least-squares mean difference, 3.1 points; 95% CI, 4.9 to 1.3). Adverse events with apremilast included diarrhea, nausea, and headache.

Conclusions

In patients with oral ulcers associated with Behet’s syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache.

DOI: 10.1056/NEJMoa1816594

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1816594