Patients. All IBD patients followed at the Saint Etienne University Hospital and starting infliximab treatment were included between December 2016 and December 2018. For each patient, we looked at their clinical evolution 24 months after treatment induction and their anti-infliximab antibody level in the induction period and during follow-up. In addition, we performed HLA phenotyping to individualize patients carrying one or two HLA-DQA1*05 alleles. Among the 207 patients treated with infliximab (IFX), only 36 were typing to HLA-DQA1*05 and could therefore be included (Fig. 1B). Patients were followed for 2 years’ post-induction.
The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice and applicable regulatory requirements. Written, informed consent was obtained from each patient included in the study. The study was approved by the CNIL (Commission Nationale Informatique et Liberté) (Number: 1849323). All authors had access to the study data and have reviewed and approved the final manuscript.
Measure of anti-drug antibodies using a drug tolerant assays. TLI and anti-IFX antibodies (ATI) concentrations were measured using the Lisa-Tracker Premium Infliximab ELISA kits (Theradiag, Marne-La-Vallee, France). This drug-sensitive assay has been developed to reduce low-affinity binding of immune complexes or interfering molecules such as the rheumatoid factor. The use of specific buffers for both binding and washing steps allows a very efficient capture of free molecules. ATI were also measured blindly with a drug-tolerant assay using anti-human lambda chain as previously described (6). Using this drug-tolerant assay positive ATA or ATI values are ≥ 2.0 µg/mL-eq. ATI were measured at 12 weeks, 6 months, 1 year and 2 years post-induction.
Clinical response was assessed clinically by physicians. In cases where the clinic was not sufficient, imaging was used to assist in the decision. Clinical failure was defined as the need to discontinue treatment due to loss of clinical response.
HLA genotyping was performed by the EFS Bellevue of Saint Etienne from patients’ whole blood after obtaining their consent.
Statistical analysis. The following variables were studied together.
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HLA-DQA1*05 allele carrier was analyzed by clinical response and then by antibody level.
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The clinical response was evaluated according to the antibody level.
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We studied the use of anti-TNF prior to treatment according to the antibody level and according to the clinical response.
Statistical analyses and figures were performed using R studio software. The p-value values lower than or equal to 0.05 were considered significant.
We use t-test to compare groups in Fig. 1A, survival analysis in Fig. 1C and Wilcoxon test in Fig. 1D.