Tanida Satoshi, Sasoh Shun, Otani Takahiro, Kubota Yoshimasa, Ban Tesshin, Ando Tomoaki, Nakamura Makoto, Joh Takashi
Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan.
J Clin Med Res. 2024 May;16(5):256-263. doi: 10.14740/jocmr5165. Epub 2024 May 29.
Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.
选择性 Janus 激酶（JAK）抑制剂单药治疗或强化粒细胞和单核细胞吸附性血液成分单采术（GMA）一直仅限于治疗难治性溃疡性结肠炎（UC）患者。此前尚无报告描述乌帕替尼（UPA）联合强化 GMA（每周两次）治疗对传统药物和阿达木单抗耐药的难治性 UC 的疗效，包括组织病理学评估以及安全性。这项回顾性研究评估了 UPA 联合强化 GMA 诱导治疗对难治性 UC 患者的 10 周临床和组织病理学疗效。在接受 UPA 联合强化 GMA 治疗的 8 例患者中（中度 UC 1 例，重度 UC 7 例），到 10 周时 50.0%的患者实现了临床缓解。10 周时组织学 - 内镜下黏膜改善和黏膜愈合的患者百分比分别为 62.5%和 12.5%。排除 1 例因对 UPA 不耐受在第 10 周停药的患者后，基线时平均梅奥总评分、内镜子评分和 C 反应蛋白浓度分别为 11.43±0.37、3±0 和 1.29±0.70mg/dL。10 周时相应的值分别为 2.28±0.77（P<0.03）、1.14±0.34（P<0.03）和 0.03±0.008mg/dL（P<0.05）。分别有 1 例患者发生带状疱疹、肌酐磷酸激酶暂时升高和贫血等不良事件。1 例患者因 UPA 导致的暂时味觉异常在第 4 周停止联合治疗。对于传统药物和抗肿瘤坏死因子-α抗体治疗失败的难治性 UC 患者，UPA 联合强化 GMA 似乎可能实现令人满意的临床缓解诱导和组织病理学改善。
