Division of Gastroenterology, Houston Methodist Hospital, Houston, Texas, USA.
Division of Gastroenterology, Vidant Medical Center, Greenville, North Carolina, USA.
J Dig Dis. 2020 May;21(5):264-271. doi: 10.1111/1751-2980.12867. Epub 2020 Jun 11.
There are limited data on using more than one biologic or small molecule drug combined to treat patients with inflammatory bowel disease. The aim of our study was to determine the effectiveness and safety of combination biologic use in inflammatory bowel disease.
We identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and a small molecule drug from 2015 to 2019 for persistent disease activity or concomitant rheumatological or dermatological disease. The primary end-point was effectiveness, based on improvements in inflammatory markers, clinical, and endoscopic remission. The secondary end-point was safety.
Of the 50 patients treated with combination therapy there were significantly more patients in clinical and endoscopic remission at follow-up compared to baseline (50% vs 14%, P = 0.0018, delta 36%, 95% confidence interval [CI] 0.13-0.53; and 34% vs 6%, P = 0.0039, delta 28%, 95% CI 0.09-0.47), respectively. Median erythrocyte sedimentation rate (17 mm/h vs 13 mm/h, P = 0.002) and C-reactive protein (5.00 mg/dL vs 2.35 mg/dL, P = 0.002) also decreased posttreatment. There were eight serious adverse events and no deaths CONCLUSIONS: Combination biologic therapy appears to be an effective option for patients with refractory inflammatory bowel disease or concomitant autoimmune disease that is inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared with biologic monotherapy; however, this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Large prospective studies are needed to confirm these findings.
关于使用一种以上生物制剂或小分子药物联合治疗炎症性肠病患者的数据有限。本研究旨在确定联合使用生物制剂治疗炎症性肠病的有效性和安全性。
我们确定了 2015 年至 2019 年期间，因持续性疾病活动或合并风湿性或皮肤病而接受两种生物制剂或生物制剂与小分子药物联合治疗的克罗恩病或溃疡性结肠炎患者。主要终点是根据炎症标志物、临床和内镜缓解的改善来评估疗效。次要终点是安全性。
在接受联合治疗的 50 例患者中，与基线相比，随访时临床和内镜缓解的患者明显更多（50%比 14%，P=0.0018，差异 36%，95%置信区间[CI]为 0.13-0.53；34%比 6%，P=0.0039，差异 28%，95%CI 为 0.09-0.47）。治疗后红细胞沉降率（17mm/h 比 13mm/h，P=0.002）和 C 反应蛋白（5.00mg/dL 比 2.35mg/dL，P=0.002）也降低。有 8 例严重不良事件，无死亡。
联合生物制剂治疗似乎是一种有效的选择，适用于生物单药治疗控制不佳的难治性炎症性肠病或合并自身免疫性疾病的患者。与生物单药治疗相比，严重感染的风险增加；然而，通过在开始联合治疗前停止免疫调节剂，可能会将这种风险降到最低。需要进行大型前瞻性研究来证实这些发现。
