IBD Unit, Digestive Disease Medicine, University of Valencia, University Clinic Hospital of Valencia, Spain.
IBD Unit, Digestive Disease Medicine, University of Valencia, University Clinic Hospital of Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, Spain.
Gastroenterol Hepatol. 2023 Nov;46(9):671-681. doi: 10.1016/j.gastrohep.2022.10.021. Epub 2022 Nov 11.
Loss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation.
A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation.
One hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71-14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05-5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48-4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78-6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39-8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1-6.93; p=0.026).
HLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare.
生物制剂的无应答和不良反应（AE）与 HLA-DQA1*05 等位基因有关。然而，临床因素或所用的生物制剂可能会影响治疗持续时间。我们的目的是评估临床和治疗因素以及 HLA 对生物治疗停药的影响。
对 2007 年至 2011 年间接受生物制剂治疗的连续 IBD 患者进行回顾性研究。主要结局是由于原发性无应答（PNR）、继发性无应答（SLR）或 AE 而停止治疗。对所有患者进行 HLA-DQA1 基因分型。回归分析用于评估治疗停药的危险因素。
共纳入 150 例（61%为男性）患者，共进行了 312 次生物制剂治疗。147 例（47%）停药，1 年、2 年和 5 年的累积概率分别为 30%、41%和 56%。使用英夫利昔单抗（p=0.006）和关节表现（p<0.05）与治疗停药相关。考虑停药原因，溃疡性结肠炎（UC）的 PNR 比例更高（HR=4.99；95%CI=1.71-14.63；p=0.003），如果生物制剂因疾病活动而使用（HR=2.32；95%CI=1.05-5.09；p=0.037），则 SLR 更高，而 AE 则更高在使用英夫利昔单抗（HR=2.46；95%CI=1.48-4.08；p<0.001）或脊柱关节炎（HR=2.46；95%CI=1.78-6.89；p<0.001）的情况下。根据生物药物，HLA-DQA1*05 与阿达木单抗联合使用时，在未接受免疫抑制剂治疗的克罗恩病（HR=3.49；95%CI=1.39-8.78；p=0.008）或无免疫调节剂联合使用时（HR=2.8；95%CI=1.1-6.93；p=0.026），SLR 更高。
在未接受免疫抑制治疗的 ADA 患者中，HLA-DQA1*05 与 IBD 患者的 SLR 相关。在接受其他生物制剂治疗的患者中，临床因素对治疗中断更为重要，主要是广泛的 UC 或肠外表现和因疾病活动而使用生物制剂。
