Yamasaki Kenshi, Yamanaka Keiichi, Zhao Yiwei, Iwano Shunsuke, Takei Keiko, Suzuki Koji, Yamamoto Toshiyuki
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Dermatology, Graduate School of Medicine, Mie University, Tsu, Japan.
J Dermatol. 2020 Dec;47(12):1383-1390. doi: 10.1111/1346-8138.15533. Epub 2020 Aug 17.
This phase 3 multicenter study, including 26-week treatment and extension periods, evaluated the efficacy and safety of adalimumab in Japanese patients with active ulcers due to pyoderma gangrenosum. Patients received adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every week starting at week 4. Of the 22 enrolled patients, 12 (54.5%, P < 0.001) achieved the primary efficacy end-point of pyoderma gangrenosum area reduction 100 (PGAR 100, defined as complete skin re-epithelialization) for the target ulcer at week 26 assessed by digital planimetry. PGAR 100 response was observed as early as week 6 (13.6%) and continued to increase over time. The mean percent change from baseline in target ulcer area was -31.8% at week 6 and -63.8% at week 26. A Physician's Global Assessment score of 0 (PGA 0, all ulcers completely clear) was achieved by two patients (9.1%) at week 6 and eight (36.4%) at week 26, while PGA 0/1 (completely/almost clear) was achieved by five (22.7%) and 12 patients (54.5%) at week 6 and 26, respectively. Mean changes from baseline in pain numeric rating scale (-1.8 at week 6 and -2.5 at week 26) and the Dermatology Life Quality Index (-3.1 at week 6 and -3.6 at week 26) improved over time. Adverse events were reported by 18 patients, most commonly infections (n = 11), and serious adverse events by four. These results suggest that adalimumab is effective and generally well tolerated in Japanese patients with active ulcers of pyoderma gangrenosum.
这项3期多中心研究包括26周的治疗期和延长期，评估了阿达木单抗对日本坏疽性脓皮病活动性溃疡患者的疗效和安全性。患者在第0周接受160毫克阿达木单抗，第2周接受80毫克，然后从第4周开始每周接受40毫克。在22名登记患者中，12名（54.5%，P<0.001）在第26周达到坏疽性脓皮病面积减少100（PGAR 100，定义为皮肤完全重新上皮化）这一主要疗效终点，该终点通过数字平面测量法评估目标溃疡。PGAR 100反应最早在第6周出现（13.6%），并随时间持续增加。目标溃疡面积相对于基线的平均变化百分比在第6周为-31.8%，在第26周为-63.8%。两名患者（9.1%）在第6周达到医师整体评估评分为0（PGA 0，所有溃疡完全清除），8名患者（36.4%）在第26周达到该评分；而在第6周和第26周，分别有5名（22.7%）和12名患者（54.5%）达到PGA 0/1（完全/几乎清除）。疼痛数字评定量表相对于基线的平均变化（第6周为-1.8，第26周为-2.5）和皮肤病生活质量指数（第6周为-3.1，第26周为-3.6）随时间有所改善。18名患者报告了不良事件，最常见的是感染（n=11），4名患者报告了严重不良事件。这些结果表明，阿达木单抗对日本坏疽性脓皮病活动性溃疡患者有效且总体耐受性良好。
