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Predictors of immunogenicity to anti-TNF therapy in IBD: results of the ABIRISK study
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Edité par CCSD -
International audience. Introduction: ABIRISK is a multicenter, prospective, non-interventional study based on cohorts of patients with IBD, multiple sclerosis, rheumatoid arthritis. Patients are included at the start of biopharmaceuticals. Biological samples are collected, to find biomarkers predictive of efficacy and immunization. We herein report the results observed in the IBD cohort of patients treated with anti TNFs. Aims and Methods: Patients treated with adalimumab (ADL) or infliximab (IFX) as a first-line therapy for active IBD were eligible. Anti-drug antibodies (ADAb) were measured a chemoluminescence drug tolerant capture ELISA assay at W0, W6, W12 and W52. Immunogenicity was defined as ADAb within the first 12 months of anti TNF treatment. Clinical activity was assessed at W6, W12, W52 and at withdrawal if the drug was discontinued. Surgical and medical history, including previous medications were reported at inclusion, while adverse events, including those related to ADAb, and concomitant medications were reported at any time points. Clinical remission was defined as a HBI≤3 in CD patients and a Mayo subscore≤4 in UC patients. Patients who discontinued ADL or IFX or who were lost to follow-up were considered as treatment failures. Results: 204 eligible patients were recruited from 17 centers (France, Belgium and Israel). 197 were included (7 screen failures) of whom 184 patients could be assessed (mean age was 36.9 (SD:13.7), 48.4% were women). There were 148 patients with CD and 36 with UC. 86 patients were treated with IFX (n=86, REM or CT-P13) and 98 with ADL. Median disease duration was 3.69 (IQR: 10.37) years. In CD, median Harvey-Bradshaw index was 6, 27 had a penetrating phenotype (B3) (IFX, n=17; ADL, n=10) and 23 had perianal fistulas (IFX, n=18 ADL, n=6). In UC, median Mayo subscore was 6. 19.6% had extra-intestinal manifestations. Concomitant immunosuppressants were prescribed in 68% and 40% of patients treated with IFX and ADA respectively. 82% and 35 % of patients treated with IFX and ADL received corticosteroids, respectively. At one year, 95 patients (51.6%) were in clinical remission, including 73 (40%) without optimization of anti-TNF therapy. ADAb were detected in 51 patients (27.7%). The immunogenicity rate for ADL and IFX was 38.8% and 15.1%, respectively. Mean time to onset of ADAb was 2.5 months, and ADAb persisted over time in 72%. Drug levels at 6 weeks of therapy were significantly lower in patients who developed ADAb. Immunogenicity was associated with non-remission at one year (58.6% in patients with ADAb vs 35.7% in patients without ADAb, p=0.008). In multivariate cox regression analysis of time to ADAb development, immunogenicity was associated with concomitant immunosuppressant (HR: 0.39 [95% CI 0.2-0.75]), anti-TNF levels at 6 weeks of therapy (HR: 0.86 [95% CI 0.8-0.91]), antibiotics usage during the study (HR: 0.3 [95% CI 0.14-0.65]) and vaccine in the year before start of anti-TNF therapy (HR: 3.1 [95% CI 1.5-6.3]). Conclusion: In IBD patients, immunogenicity towards anti TNFs is associated with a lower remission rate and lower drug levels. Concomitant immunosuppressants and antibiotics are associated with a lower risk of immunogenicity while vaccine received before the start of anti TNF are associated with an increased risk of immunogenicity.
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