Galdakao, Spain.
Barcelona, Spain.
Aliment Pharmacol Ther. 2020 May;51(9):870-879. doi: 10.1111/apt.15687. Epub 2020 Mar 17.
Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD).
To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice.
We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment.
One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs <10 ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3 months. Of 62 patients with perianal disease, complete closure was observed in 8% (n = 5) of patients with perianal fistulas, with 34% (n = 21) showing partial response. Treatment was maintained for a median of 6 months (IQR, 2-16). After a median clinical follow-up of 24 months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P = 0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC.
Tacrolimus shows a clinical benefit in both CD and UC after 3 months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.
他克莫司是一种钙调神经磷酸酶抑制剂，常用于预防肾和肝移植中的排斥反应。关于其在炎症性肠病（IBD）患者中的可能用途，已有一些有限但有利的数据。
评估他克莫司在临床实践中用于 IBD 患者的疗效和安全性。
我们在西班牙的 22 个中心进行了一项回顾性、多中心研究。所有接受口服他克莫司治疗肠内或肛周 IBD 的成年患者均纳入研究。3 个月后，通过 Harvey-Bradshaw 指数和部分 Mayo 评分评估临床反应。肛周疾病通过瘘管引流评估。
共纳入 143 例患者（平均年龄 38 岁；51%为男性；中位疾病病程 110 个月）。在溃疡性结肠炎（UC）（n=58）中，部分 Mayo 评分在 3 个月后从中位数 6 降至 3（P=0.0001），而在克罗恩病（CD）（n=85）中，Harvey-Bradshaw 指数在 3 个月后从中位数 9 降至 7（P=0.011）。在 CD 患者中，诱导期血他克莫司浓度（>10ng/mL 与 <10ng/mL；比值比 0.23，95%置信区间 0.05-0.87）和同时使用硫嘌呤（比值比 0.18，95%置信区间 0.04-0.81）与 3 个月时较低的临床疾病活动度相关。在 62 例肛周疾病患者中，8%（n=5）的肛周瘘患者完全闭合，34%（n=21）的患者有部分反应。中位治疗时间为 6 个月（IQR，2-16）。中位临床随访 24 个月（IQR，15-57）后，治疗相关不良事件发生率为 34%，与血药浓度相关（P=0.021）。最后，120 例（84%）患者停用他克莫司，通常是因为无反应或失去反应。有 3 例（2%）患者随后被诊断为癌症。总的手术率为 39%，UC 中有 33%的结肠切除术率。
他克莫司在 CD 和 UC 患者中治疗 3 个月后显示出临床获益，但长期有效性和频繁的不良事件仍然是临床实践中的重要问题。
