a Department of Gastroenterology, Inflammatory Bowel Disease Unit , Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC) , Madrid , Spain.
b Department of Gastroenterology and CIBERehd , Hospital Universitario La Fe , Valencia , Spain.
Curr Med Res Opin. 2019 Jul;35(7):1297-1304. doi: 10.1080/03007995.2019.1579557. Epub 2019 Mar 13.
To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment. This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50 mg every 4 weeks (q4wk) was optimized before week 14 to 100 mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival. A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80 kg were assigned to a golimumab maintenance dose of 50 mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50 mg q4wk were optimized to 100 mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12 months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal. Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.
评估在接受戈利木单抗诱导治疗后应答不足的溃疡性结肠炎（UC）患者中早期优化戈利木单抗剂量的结局。这项观察性、多中心队列研究纳入了中重度活动期 UC 且对皮下戈利木单抗诱导剂量应答不足的患者，这些患者在第 14 周前将基于体重的戈利木单抗维持剂量（欧洲标签）从 50mg 每 4 周（q4wk）优化至 100mg q4wk。在第 14 周，我们使用部分 Mayo 评分评估临床应答和缓解。在长期随访中，我们评估了戈利木单抗无失败生存和结肠切除无生存的累积概率。共纳入 209 例接受戈利木单抗诱导剂量的患者，其中 151 例（72.2%）体重<80kg 患者被分配至戈利木单抗维持剂量 50mg q4wk。24 例（15.9%[总体 12.5%]）患者在第 14 周前将计划剂量 50mg q4wk 优化至 100mg q4wk，这些患者构成了研究人群。在第 14 周，16 例患者（66.7%，95%CI 45.7-87.6）获得临床应答，其中 12 例患者无皮质类固醇治疗。4 例患者（16.7%）获得皮质类固醇缓解。中位随访 12 个月（IQR 10-22）后，13 例患者（54.2%）维持临床获益。14 周时获得临床应答的 16 例患者中有 13 例（81.2%）在最后一次随访时维持临床获益。所有患者均避免结肠切除术。没有患者减少戈利木单抗剂量。没有因不良事件导致戈利木单抗停药。在三分之二的 UC 患者中，早期优化戈利木单抗剂量可在第 14 周诱导临床应答，并在超过一半的患者中带来长期临床获益。
