Real-world incidence of inflammatory bowel disease among patients with other chronic inflammatory diseases treated with interleukin-17a or phosphodiesterase 4 inhibitors

<b>Objectives:</b> (1) To assess the real-world incidence of inflammatory bowel disease (IBD) in patients with or without other chronic inflammatory diseases (CIDs), and (2) to understand whether IBD incidence differs in CID patients receiving IL-17a signaling antagonists (anti-IL-17a) or phosphodiesterase 4 inhibitors (PDE4i) versus patients using a biologic not indicated for IBD or biologic-naïve patients. <b>Methods:</b> The MarketScan® Research Databases (1/2010-7/2017) were used. A CID population was created from patients with ankylosing spondylitis, psoriatic arthritis, psoriasis, or rheumatoid arthritis (RA). The CID population was stratified into different cohorts based on the baseline treatments received: (1) IL-17a, (2) PDE4i, (3) biologic-naïve, (4) and non-IBD-indicated biologic (i.e., biologics not indicated for the treatment of IBD excluding anti-IL-17a and PDE4i); a non-CID cohort was also created. The one-year incidence rate (IR) of IBD was compared between cohorts using a logistic regression model adjusting for baseline characteristics. <b>Results:</b> CID cohorts included older patients than the non-CID cohort (mean age range: 48.4-54.4 versus 46.3 years). The one-year IR of IBD was 1.41% in the IL-17a cohort (N = 355), 0.68% in the PDE4i cohort (N = 2,195), 0.47% in the biologic-naïve cohort (N = 424,767), 0.51% in the non-IBD-indicated biologic cohort (N = 56,317) cohort, and 0.25% in the non-CID cohort (N = 1,008,436). After one year of follow-up, the odds of having IBD were 2.85 (<i>P</i> = 0.0213) and 1.42 (<i>P</i> = 0.1891) times higher in the IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (<i>P</i> = 0.0253) and 1.21 (<i>P</i> = 0.4978) times higher compared to the non-IBD-indicated biologic cohort. Similar results were observed in sensitivity analyses where patients with RA only were excluded (since anti-IL-17a and PDE4i agents are not indicated for RA). <b>Conclusions:</b> Anti-IL-17a treatment was associated with a nearly 3-fold higher risk of IBD in CID patients. Treatment decisions for patients with CIDs should take into account the risk of developing of IBD.

<b>研究目标：</b> (1) 评估合并或不合并其他慢性炎症性疾病（chronic inflammatory diseases, CIDs）的患者中，炎症性肠病（inflammatory bowel disease, IBD）的真实世界发病率；(2) 明确接受IL-17a信号拮抗剂（anti-IL-17a）或磷酸二酯酶4抑制剂（phosphodiesterase 4 inhibitors, PDE4i）的慢性炎症性疾病患者，与使用未获批用于IBD适应证的生物制剂或生物制剂初治（biologic-naïve）患者相比，其IBD发病率是否存在差异。<b>研究方法：</b> 本研究采用MarketScan®研究数据库（2010年1月—2017年7月）的数据。慢性炎症性疾病队列纳入强直性脊柱炎、银屑病关节炎、银屑病或类风湿关节炎（rheumatoid arthritis, RA）患者，并按基线治疗方案分为4个亚组：(1) IL-17a拮抗剂组，(2) PDE4i组，(3) 生物制剂初治组，(4) 未获批用于IBD适应证的生物制剂组（即排除anti-IL-17a与PDE4i外，未获批用于IBD治疗的生物制剂）；同时设置非慢性炎症性疾病队列。采用logistic回归模型校正基线特征，比较各组的1年IBD发病率（incidence rate, IR）。<b>研究结果：</b> 慢性炎症性疾病各组患者的平均年龄高于非慢性炎症性疾病队列（平均年龄范围：48.4~54.4岁 vs 46.3岁）。各组1年IBD发病率分别为：IL-17a拮抗剂组（N=355）1.41%，PDE4i组（N=2195）0.68%，生物制剂初治组（N=424767）0.47%，未获批用于IBD适应证的生物制剂组（N=56317）0.51%，非慢性炎症性疾病队列（N=1008436）0.25%。随访1年后，与生物制剂初治组相比，IL-17a拮抗剂组与PDE4i组发生IBD的比值比分别为2.85（P=0.0213）和1.42（P=0.1891）；与未获批用于IBD适应证的生物制剂组相比，该两组比值比分别为2.86（P=0.0253）和1.21（P=0.4978）。在排除仅类风湿关节炎患者的敏感性分析中得到了一致结果（因anti-IL-17a与PDE4i药物未获批用于类风湿关节炎适应证）。<b>研究结论：</b> 慢性炎症性疾病患者接受anti-IL-17a治疗时，发生IBD的风险较对照组升高近3倍。慢性炎症性疾病患者的临床治疗决策应充分考虑发生IBD的风险。