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Background HLA-DQA1*05 Carriage is associated with development of anti-drug antibodies to infliximab in patients With Crohn’s Disease (Sazonovs et al. Gastroenterology 2019). Our group has shown that the presence of this allele is also an independent predictor of secondary loss of response to infliximab (Guardiola J, ECCO 2019) and adalimumab (Guardiola J ECCO 2020). However, the impact of the HLA-DQA1 * 05 allele on the initial response and persistence of IFX in the first months of treatment is unknown. Methods This is a retrospective cohort study from a prospectively maintained data base at the Hospital Universitari de Bellvitge (third level teaching hospital) Patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who initiated IFX to induce remission and who had been followed up for failure or a minimum of 6 months were included. Failure at IFX was defined as the need of escalation or change treatment, surgery, or hospitalization for the first 6 months. Results 99 patients (65 MC, 34 CU) were included. In 63 (63.63%) IFX failed. 39 (39%) were carriers of the HLA-DQA1 * 05 allele. In multivariate analysis, HLA-DQA1*05 carriage (HR 1.9, 95% CI 1.14–3.31 p=0.015), the use of immunomodulators (HR 0.38, 95% CI 0, 23–0.66 p = 0.001) and suffering a CU vs. MC (HR 1.72, 95% CI 1.02–2.89 p = 0.041) were independent predictors of IFX failure. HLA-DQA1 * 05 was also associated with non-persistence of treatment (HR 2,4,95% CI1.45–3.99 p = 0.001). Figure A Conclusion HLA-DQA1*05 carriage is common in patients with IBD and it’s associated with a marked increase in the risk of loss of response to infliximab. Testing for HLA-DQA1*05 would allow treatment to be tailored according to the risk of loss of response.

Background AntiTNF therapeutic drug monitoring is currently performed at trough, immediately before drug administration. However, in clinical practice when subcutaneous medications are used, blood extractions often do not coincide with that moment. The aim of this study was to know if adalimumab levels measured between injections are sufficiently similar to trough levels to be used in clinical practice in a similar way. Methods 295 adalimumab level determinations performed at different time points of 99 injection cycles in 55 patients with inflammatory bowel disease (IBD) were included in the study. 51 patients received 40mg every 2 weeks and 4 patients received 80mg every 2 weeks. Results Median adalimumab levels (IQR) at trough, between days 1–4, 5–8 and 9–13 were 10.6 (6–12), 12.3 (7–18), 13 (7–19) and 10.8 (8–12), respectively. The median differences between trough level and days 1–4, 5–8 and 9–13 were 1.7 (IC 95% 1–2.3) (p < 0.001), 2.3 (IC 95% 1.5–3.1) (p < 0.001), 0.6 (IC 95% –0.2–1.3) (p = 0.13), respectively. Conclusion Adalimumab levels between days 9 and 13 from drug injection are very similar to trough level and could be interpreted clinically at the same way. Adalimumab levels between days 1 and 8 are significantly higher, although, differences are small.

Background Loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) occurs in up to 50% of patients with inflammatory bowel disease (IBD). The ability to predict which patients are likely to lose response would allow therapies to be tailored to the patient’s characteristics. Immunogenicity is a common cause of LOR. Recently, a GWAS performed using the PANTS cohort demonstrated that carriage of one or more HLA-DQA1*05 alleles confers an increased risk of immunogenicity to anti-TNF therapy (Sazonovs et al. Gastroenterology 2019). We found that HLA-DQA1*05 carriage also identified patients at increased risk of clinical LOR to infliximab (Guardiola et al. ECCO 2019). The aim of our study was to know if carriage of a HLA-DQA1*05 allele is also associated with secondary LOR to adalimumab (ADA) in patients with Crohn’s disease (CD). Methods This is a retrospective cohort study from a prospectively maintained data base. Patients were included if they had achieved response to ADA. LOR was defined as recurrence or worsening of IBD-related symptoms that required a change or intensification in treatment, hospitalisation or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Results We included 53 patients with Crohn’s disease, followed up to LOR (n = 31, 58%) or a median of 51 months (IQR 35–74). Forty-five per cent were carriers of an HLA-QA1*05 allele. HLA-DQA1*05 carriage was associated with LOR both, upon univariate analysis (HR 2.1 (95% CI 1.1–4.3), p = 0.04) and upon multivariate analysis, after adjusting for immunomodulators use, smoking status and BMI (HR 2.74 (95% CI 1.2–6.2), p = 0.02) (Figure 1). The cumulative persistence rates of ADA after adjusting for immunomodulators use was significantly lower in HLA-DQA1*05 carriers compared with non-carriers (HR 4 (95% CI 1.2–15.5), p = 0.02) (Figure 2). Conclusion HLA-DQA1*05 carriage is frequent and it is associated with a marked increase in the risk of LOR to ADA. HLA-DQA1*05 may become a clinically meaningful genetic marker that could allow for treatment to be tailored according to the risk of LOR, which is a step towards personalised medicine.