Kolar M, Duricova D, Bortlik M, Hruba V, Machkova N, Mitrova K, Malickova K, Lukas M, Lukas Milan
IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.
Dig Dis. 2017;35(1-2):91-100. doi: 10.1159/000453343. Epub 2017 Feb 1.
The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse.
Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort.
Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts.
Switching of IBD patients from original to biosimilar IFX is effective and safe.
关于生物类似药英夫利昔单抗（IFX）治疗炎症性肠病（IBD）患者的疗效及安全性的证据较少。
纳入连续就诊于我们中心的IBD患者。一个队列由2015年1月至3月期间从原研IFX转换为生物类似药IFX并进行前瞻性随访的患者组成。第二个队列包括2015年1月至2016年1月期间开始治疗的既往未使用过抗肿瘤坏死因子α药物的患者，这些患者进行回顾性评估。使用标准临床指标、内镜评估和实验室参数（血细胞计数、C反应蛋白（CRP）和粪便钙卫蛋白（FC））评估疾病活动度。还测量了谷浓度和抗药抗体（ATI）。转换治疗的患者在转换后56周（W56）进行评估，初治队列的患者在第14周（W14）和第46周（W46）进行评估。
74例IBD患者转换为生物类似药IFX，119例初治患者开始使用该制剂进行治疗。大多数转换治疗的患者疾病活动度保持稳定（第0周（W0）与W56时的缓解率：72.2%对77.8%；W0与W56之间Harvey-Bradshaw指数和简单临床结肠炎活动指数的中位数差异均为0）。比较W0和W56时，CRP（4.3±8.0对3.3±3.8mg/L；p=0.89）和FC（135±153对199±225μg/g；p=0.17）无显著差异。总体而言，92%的克罗恩病（CD）患者和83%的溃疡性结肠炎（UC）患者对生物类似药IFX诱导治疗（W14）有反应。在W46时，CD患者的反应率为86%，UC患者为64%。此外，一半的UC患者在W14时实现黏膜愈合，95%的CD患者在W46时肛周疾病得到改善。在该队列中，观察到明显的激素节省效应。转换治疗的患者免疫原性未增加（ATI阳性率：9.5%对6.0%，p=0.54），两个队列中不良事件的类型和发生率与原研制剂相当。
IBD患者从原研IFX转换为生物类似药IFX是有效且安全的。
