Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
BMC Gastroenterol. 2019 Sep 5;19(1):162. doi: 10.1186/s12876-019-1067-0.
Plaque psoriasis and inflammatory bowel disease (IBD) are both chronic immune-mediated inflammatory diseases with an overlapping genetic profile and have been linked in epidemiological studies. Psoriasis and IBD share similar components in their inflammatory pathways and animal and human studies have suggested a potential role for targeting interleukin (IL)-17 with novel antibody therapies in the treatment of these diseases. These studies, while promising for psoriasis, have been associated with deterioration in patients with IBD. Post-hoc analyses of clinical trials involving Ixekizumab revealed adverse outcomes in a small cluster of patients with IBD, prompting recommendations to monitor this population with the use of this drug.
Forty-two year old Caucasian male with treatment-refractory chronic plaque psoriasis who developed new onset diarrheal illness and rectal bleeding following a 12 week induction period with Ixekizumab (anti-IL-17 neutralizing antibody). Colonoscopy revealed severe ulceration throughout the ascending and transcending colon. Histopathology, combined with endoscopic findings, led to a diagnosis of Crohn's-like colitis. The patient's anti-IL-17 medication was discontinued and endoscopic remission was induced with the use of corticosteroids, escalated anti-TNF therapy and eventually anti IL-12/23 neutralizing antibody (ustekinumab).
Murine studies implicate IL-17 and the downstream effects of its inhibition, in the breakdown of the gut epithelial layer, the disruption of normal host immune responses and the propagation of intestinal inflammation. The increasing use of IL-17 inhibitors has led to reports of exacerbation and potential development of inflammatory bowel disease. While clinical trials have revealed clusters of new inflammatory bowel disease cases amongst psoriasis patients using an IL-17 inhibitor, there remains a lack of evidence to suggest a causal relationship. This is the first case report of de-novo severe Crohn's-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.
斑块状银屑病和炎症性肠病（IBD）都是慢性免疫介导的炎症性疾病，具有重叠的遗传特征，并在流行病学研究中相关联。银屑病和 IBD 在其炎症途径中具有相似的成分，动物和人体研究表明，针对白细胞介素（IL）-17 的新型抗体疗法在治疗这些疾病方面可能具有潜在作用。这些研究虽然对银屑病有希望，但与 IBD 患者的病情恶化有关。Ixekizumab 临床试验的事后分析显示，一小部分 IBD 患者出现不良结局，促使人们建议在使用该药物时监测该人群。
一名 42 岁的白人男性，患有难治性慢性斑块状银屑病，在接受 Ixekizumab（抗 IL-17 中和抗体）12 周诱导期后出现新发腹泻和直肠出血。结肠镜检查显示升结肠和横结肠有严重溃疡。组织病理学，结合内镜检查结果，诊断为克罗恩样结肠炎。该患者停止使用抗 IL-17 药物，并使用皮质类固醇、升级抗 TNF 治疗，最终使用抗 IL-12/23 中和抗体（ustekinumab）诱导内镜缓解。
鼠类研究表明，IL-17 及其抑制的下游效应，在肠道上皮层的破坏、正常宿主免疫反应的中断和肠道炎症的传播中起作用。IL-17 抑制剂的使用越来越多，导致银屑病患者使用 IL-17 抑制剂后炎症性肠病恶化和潜在发展的报告。虽然临床试验显示，在使用 IL-17 抑制剂的银屑病患者中出现了新的炎症性肠病病例群，但仍缺乏证据表明存在因果关系。这是首例与 Ixekizumab 相关的新发性严重克罗恩样 IBD 病例报告，需要使用升级的抗 TNF 治疗进行抢救，并强调了在接受 IL-17 抑制剂治疗的患者中密切监测的重要性，特别是在那些有炎症性肠病已知危险因素的患者中。
