OP37 Effect of the HLA-DQA1*05 allele on the efficacy of ustekinumab in patients with Crohn's Disease. Multicenter study based on the ENEIDA registry of GETECCU
Authors: Guardiola Capón J , Iborra M , Padró A , de la Peña L , Serra K , Martin-Arranz M D , Domènech E , Fernandez A , Mesonero F , Gonzalez-Muñoza C , Ferreiro-Iglesias R , Navarro P , Martín-Cardona A , Sicilia B , Sierra-Ausin M , Calvet X , Marquez L , de Francisco R , Cañete F , Gutierrez A , García-López S , Rivero M , Hinojosa J , Iglesias-Flores E , Nos P , Riestra S , Bosca-Watts M , Zabana Y , Castro B , Barreiro M , Garcia-Planella E , Ricart E , De Francisco R , Suris G , Ruiz-Cerulla A , Rodriguez-Alonso L , Orobitg J , Rodríguez-Moranta F 
Published: January 2024

Abstract

Background
HLA-DQA1*05 carriage is associated with the development of anti-drug antibodies and loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) in patients with inflammatory bowel diseases (IBD)1. Ustekinumab has shown very low rates of immunogenicity and presumably will not be affected by this risk. Identifying patients at high risk of treatment failure would be important when selecting therapy for IBD.
The objective of this analysis was to investigate the relationship between the HLA- QA1*05 allele and ustekinumab on development of LOR and drug persistency.

Methods
This is a retrospective cohort study from a prospectively maintained ENEIDA registry. LOR was defined as recurrence or worsening of IBD related symptoms that required a change or intensification in treatment, hospitalization or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. The HLA-DQA1*05 allele was determined from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits.

Results
204 patients with Crohn's disease were included. Previous exposure to biological drugs was 96% (61% ≥2 biological drugs). Basal faecal calprotectin levels were 907±970μg/g and PCR levels 16.2±25 mg/dL. The median follow-up was 417±154 days. During this period, 25%, 16% and 13% of the patients required drug intensification, hospitalization or surgery, respectively. 43% of the patients included were carriers of one or two copies of the HLA-DQA1*05 allele. The presence/absence of this allele was not associated with LOR to ustekinumab (20% vs 16%, p = ns) nor with drug withdrawal (11% vs 6%, p = ns). In the multivariate analysis (COX regression), only the number of previous biological drugs was associated with ustekinumab persistency.

Conclusion
The presence of the HLA-DQA1*05 allele is not related to LOR or persistency of ustekinumab treatment. First-line treatment with ustekinumab rather than anti-TNF agents may be considered in HLA-DQA1*05-positive patients, particularly when the use of a concomitant immunosuppressant is contraindicated.
1. Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, et al. PANTS Consortium. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease. Gastroenterology. 2020 Jan;158(1):189-199.