López De-La-Cruz Julia, Gomollón Fernando, Louro Javier, López Pérez Juan, Nocito Colon María Mercedes, Gallego Llera Beatriz, García-Mateo Sandra, Martínez-Domínguez Samuel J, Aso Gonzalvo María Concepción, Gargallo-Puyuelo Carla J
Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza, Spain.
Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
J Crohns Colitis. 2025 Jun 4;19(6). doi: 10.1093/ecco-jcc/jjae178.
HLADQA105 is recently associated with heightened immunogenicity to anti-tumor necrosis factor (TNFα). We aimed to determine whether HLADQ105 is a risk factor for primary non-response, loss of response (LOR), or adverse events (AE) to first-line anti-TNFα in patients with inflammatory bowel disease.
We performed a retrospective observational study enrolling biologic naïve patients with Crohn's disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients.
We enrolled 408 patients who started first-line infliximab (n = 211) and adalimumab (n = 197), with a mean follow-up of 7.6 years. Primary response at Week 24 occurred in 347 (85.0%), LOR in 133 (38.3%), and AE in 93 (22.8%). The HLADQA105 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA105 was an independent risk factor for LOR (adjusted hazard ratio [aHR] = 1.80, 95% CI = 1.21-2.67) and immunogenicity (aOR = 3.44, 95% CI = 1.12-11.92). HLADQA103 was a protective factor against LOR (aHR = 0.42, 95% CI = 0.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA105 increased the risk of LOR to infliximab but not to adalimumab and HLADQA103 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab, and the co-presentation of at least one allele of the HLADQA103 and HLADQA1*05 were risk factors for AE.
HLADQA105 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA103 seems to play a protective role against LOR, particularly adalimumab. Female sex and infliximab are risk factors for AE.
HLADQA105最近被认为与抗肿瘤坏死因子（TNFα）的免疫原性增强有关。我们旨在确定HLADQ105是否是炎症性肠病患者对一线抗TNFα治疗原发性无反应、反应丧失（LOR）或不良事件（AE）的危险因素。
我们进行了一项回顾性观察研究，纳入了2000年至2021年开始使用阿达木单抗或英夫利昔单抗的初治克罗恩病和溃疡性结肠炎患者。测定了所有患者的HLA-DQA1基因型，并对98例患者进行了免疫原性检测。
我们纳入了408例开始一线使用英夫利昔单抗（n = 211）和阿达木单抗（n = 197）的患者，平均随访7.6年。24周时的原发性反应发生在347例（85.0%），反应丧失发生在133例（38.3%），不良事件发生在93例（22.8%）。185例（43.3%）患者检测出HLADQA105。在多变量分析中，未发现原发性反应的危险因素。HLADQA105是反应丧失（调整后风险比[aHR]=1.80，95%可信区间[CI]=1.21-2.67）和免疫原性（调整后比值比[aOR]=3.44，95%CI = 1.12-11.92）的独立危险因素。HLADQA103是反应丧失的保护因素（aHR = 0.42，95%CI = 0.20-0.88）。按抗TNF类型进行分层分析显示，HLADQA105增加了对英夫利昔单抗反应丧失的风险，但对阿达木单抗没有影响；HLADQA103降低了对阿达木单抗反应丧失的风险，但对英夫利昔单抗没有影响。女性、英夫利昔单抗以及HLADQA103和HLADQA1*05至少一个等位基因的共同出现是不良事件的危险因素。
HLADQA105与反应丧失和免疫原性的较高风险相关，尤其是对英夫利昔单抗。HLADQA103似乎对反应丧失起保护作用，尤其是对阿达木单抗。女性和英夫利昔单抗是不良事件的危险因素。
