Nishio Masafumi, Ishii Yoshito, Hashimoto Yu, Otake Haruka, Ogashiwa Tsuyoshi, Tsuda Saya, Yasuhara Hisae, Saigusa Yusuke, Kimura Hideaki, Maeda Shin, Kunisaki Reiko
a Inflammatory Bowel Disease Center , Yokohama City University Medical Center , Yokohama , Japan.
b Department of Gastroenterology , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
Scand J Gastroenterol. 2018 Oct-Nov;53(10-11):1236-1244. doi: 10.1080/00365521.2018.1511825. Epub 2018 Oct 24.
Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC.
Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan-Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered.
Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis.
The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.
钙调神经磷酸酶抑制剂对皮质类固醇难治性溃疡性结肠炎（UC）患者非常有效。当钙调神经磷酸酶抑制剂治疗失败时，可考虑使用阿达木单抗以避免结肠切除术。这种序贯替代挽救疗法的疗效和安全性尚不清楚。因此，本研究旨在调查在皮质类固醇难治性UC中钙调神经磷酸酶抑制剂治疗失败后阿达木单抗的短期和长期疗效及安全性。
本回顾性、观察性、单中心研究纳入了皮质类固醇难治性UC发作且对钙调神经磷酸酶抑制剂无反应并接受阿达木单抗持续挽救治疗的患者。使用Kaplan-Meier方法计算结肠切除术的累积发生率。根据拉赫米列维茨指数评估临床缓解和反应情况。计算结肠切除术的累积发生率。确定临床缓解和结肠切除术的预测因素。在安全性评估中，考虑阿达木单抗给药后发生的任何不良事件。
纳入41例患者；78%患有广泛性结肠炎，87%患有中度至重度结肠炎。17例患者（41%）在随访期间接受了结肠切除术。在注射阿达木单抗后的第8周、26周和52周，分别有27%、39%和32%的患者实现临床缓解。不良事件发生率为17%，包括1例结核病。
首次研究了阿达木单抗对钙调神经磷酸酶抑制剂难治性UC的疗效。在三分之二皮质类固醇难治性UC且钙调神经磷酸酶抑制剂治疗失败的患者中，阿达木单抗治疗避免了结肠切除术的需要。然而，需要注意避免不良事件，尤其是感染。
