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P297 HLA-DQA1*05 allele and its association with the secondary loss of response to infliximab in patients with Inflammatory Bowel Disease.

Angulo McGrath, I.(1);Bracho González, M.(1);Ocaña Ledesma, A.(1);Olmedo Martín, R.V.(1);

(1)Hospital Regional Univertitario de Málaga, Gastroenterology, Málaga, Spain

Background

It is estimated that around 40-50% of patients with Inflamatory Bowel Disease (IBD) will experience a secondary loss of response (SLR) to infliximab, being the immunogenicity a fundamental mechanism. The HLA class II allele, DQA1*05, that codifies the adaptative immune response, is present in approximately 40% of patients treated with anti-TNF, and has been recently associated with a higher probability of immunogenicity, secondary loss of response and discontinuation of anti-TNF therapy.

The aim of this study was to evaluate if the presence of one o more copies of this allele is associated with a higher chance of SLR in patients with IBD treated with infliximab in our project study area.

Methods

Retrospective observational cohort study. We conducted a review of our unit’s database, including in the study patients with IDB treated with infliximab that responded to the induction, in which the presence of HLA-DQA1*05 had been tested. SLR was defined as the recurrence or worsening of symptoms that entailed a treatment change or intensification, hospitalization or surgery. The predictive factors for SLR were identified through a uni and multivariate Cox regression analysis.

Results

88 patients with IDB were included (63 with Crohn’s Disease and 25 with Ulcerative Colitis), followed up to the SLR (52,3%) or a median of 35 months (IQR=58). 42% of these patients were carriers of the HLA-DQA1*05 allele. Patients’ clinical features are gathered in table 1. In the univariate analysis the disease duration in years (HR=0,9, IC 95% 0,85-0,97, p=0,008) and the presence of HLA-DQA1*05 (HR=2,27, IC 95% 1,07-4.83, P=0,03) were associated with the SLR. In the multivariate analysis, adjusted for smoking, previous restrictive surgery, years of evolution of the disease and the presence of combined immunosuppressive therapy, only the presence of HLA-DQA1*05 remained associated to the SLR (HR=2,32, IC 95% 1,07-5,02, p=0,03). Figure 1.

Variable (n=88) N(%)/Median (IQR)
Sex (men) 46(52,3)
Age (years) 39(20)
Tobacco use 17(19,3)
Type of IBD
UC
CD

25(28,4)
63(71,6)
UC location
E2
E3

7(28)
18(72)
CD location
L1
L2
L3
L1+L4
Perianal

18(28,6)
14(22,2)
27(42,9)
3(4,8)
22(35,5)
CD phenotype
B1
B2
B3

41(65,1)
10(15,9)
12(19)
Extraintestinal manifestations 12(14)
Previous resective surgery 8(9,1)
Presence of HLA-DQA1*05 37(42)
Secondary loss of response 46(52,3)
Withholding treatment (maximum follow-up) 74(84,1)

Table 1. Patients' clinical features.

Figure 1. Cox Regression.
Figure 1. Cox Regression.

Conclusion

The presence of the HLA-DQA1*05 allele is frequent in patients with IBD, and it is associated with a secondary loss of response to infliximab. If confirmed with prospectively designed studies, the determination of this allele could guide physicians on the therapeutic decision making, advancing towards a more accurate medicine.

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