Sud Sukrit, Sachdeva Sanjeev, Puri Amarender Singh
Department of Gastroenterology, G B Pant Institute of Postgraduate Medical Education and Research, New Delhi 110 002, India.
Medanta -The Medicity Hospital, Gurugram, 122 006, India.
Indian J Gastroenterol. 2021 Dec;40(6):598-603. doi: 10.1007/s12664-021-01185-5. Epub 2021 Dec 31.
Between 20% and 40% of patients with severe ulcerative colitis (UC) are either steroid-refractory UC (SRUC) or steroid-dependent UC (SDUC). Tacrolimus is an oral and relatively inexpensive drug, which has been extensively used in Japan for steroid-refractory and steroid-dependent disease.
Patients diagnosed with SDUC/SRUC were treated with tacrolimus 0.05-0.1 mg/kg in this prospective study. Clinical Mayo score (CMS) and UC Endoscopic Index of Severity (UCEIS) were evaluated prior to starting the drug and subsequently after 8 weeks. 5-Aminosalicylic acid agents (5-ASA) and immunomodulators were continued if the patients were previously on these drugs. Clinical response at 8 weeks was defined as decrease in CMS by at least 3 points. Clinical remission was defined as CMS ≤2 and combined remission as CMS≤2 with UCEIS <3.
Fifty-two patients (29 males) with a mean age of 35.1± 12.8 years with predominantly E3 disease (71%) were prospectively evaluated in this study. SDUC and SRUC were diagnosed in 31 and 21 patients, respectively. Seven failed treatment within 8 weeks, four were subjected to surgery, and 3 were switched to infliximab. Forty-two patients continued tacrolimus for 8 weeks. Mean CMS and UCEIS prior to starting tacrolimus were 6 ± 1.1 and 4.8 ± 1.1, respectively. At 8 weeks, median CMS and UCEIS decreased to 2.6 ± 1.7 and 2.7 ± 1.3, respectively. Clinical response was documented in 29 patients (56%) at week 8 whereas clinical remission was seen in 25 patients (48%). Combined clinical and endoscopic remissions were seen in 18 patients (35%). Except for a single patient who developed reversible renal dysfunction, no other adverse event was observed.
Our results show that tacrolimus is effective in inducing a clinical response in 56% of patients with SDUC and SRUC. In view of its low cost and safety profile, it may be considered first-line therapy for SDUC/SRUC.
20%至40%的重症溃疡性结肠炎（UC）患者属于激素难治性UC（SRUC）或激素依赖性UC（SDUC）。他克莫司是一种口服且相对便宜的药物，在日本已被广泛用于治疗激素难治性和激素依赖性疾病。
在这项前瞻性研究中，对诊断为SDUC/SRUC的患者使用0.05 - 0.1毫克/千克的他克莫司进行治疗。在开始用药前以及用药8周后评估临床梅奥评分（CMS）和UC内镜严重程度指数（UCEIS）。如果患者之前正在使用5 - 氨基水杨酸制剂（5 - ASA）和免疫调节剂，则继续使用。8周时的临床反应定义为CMS至少降低3分。临床缓解定义为CMS≤2，联合缓解定义为CMS≤2且UCEIS <3。
本研究前瞻性评估了52例患者（29例男性），平均年龄35.1±12.8岁，主要为E3型疾病（71%）。分别有31例和21例患者被诊断为SDUC和SRUC。7例患者在8周内治疗失败，4例接受了手术，3例改用英夫利昔单抗。42例患者继续使用他克莫司8周。开始使用他克莫司前的平均CMS和UCEIS分别为6±1.1和4.8±1.1。在8周时，CMS和UCEIS的中位数分别降至2.6±1.7和2.7±1.3。8周时29例患者（56%）有临床反应，25例患者（48%）出现临床缓解。18例患者（35%）实现了临床和内镜联合缓解。除1例出现可逆性肾功能不全的患者外，未观察到其他不良事件。
我们的结果表明，他克莫司对56%的SDUC和SRUC患者诱导临床反应有效。鉴于其低成本和安全性，它可被视为SDUC/SRUC的一线治疗药物。
