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P414 Obesity is associated with a higher risk of immunogenicity to adalimumab, but not to infliximab in patients with Inflammatory Bowel Disease

Mahmoud, R.(1);Schultheiss, J.(1);Louwers, J.(1);van der Kaaij, M.(1);van Hellemondt, B.(1);Mahmmod, N.(2);van Boeckel, P.(2);Jharap, B.(3);Fidder, H.(1);Oldenburg, B.(1);

(1)University Medical Centre Utrecht, Division of Internal Medicine and Dermatology- Department of Gastroenterology and Hepatology, Utrecht, The Netherlands;(2)St. Antonius Hospital, Division of Internal Medicine- Department of Gastroenterology and Hepatology, Nieuwegein, The Netherlands;(3)Meander Medical Centre, Division of Internal Medicine- Department of Gastroenterology and Hepatology, Amersfoort, The Netherlands

Background

Globally, the prevalences of both inflammatory bowel diseases (IBD) and obesity have increased over the past decades. Recently, obesity has been linked to treatment failure in anti-TNF-treated patients with inflammatory bowel disease (IBD). We assessed whether obesity was associated with an increased risk of treatment failure and immunogenicity (i.e. anti-drug antibodies) among IBD patients treated with adalimumab (ADA) or infliximab (IFX).

Methods

This was a multicenter, retrospective cohort study of adult patients with IBD,  treated with ADA or IFX for at least four months between 2011-2019 at a general hospital or a tertiary referral center. Obesity was defined as body mass index (BMI) >30kg/m2. Adjusted hazard rates (aHR) were calculated by mixed-effects Cox regression analysis, accounting for multiple treatment episodes in individual patients and adjusted for sex, prior anti-TNF exposure, immunomodulator use, IBD phenotype (ulcerative colitis versus Crohn’s disease), age, disease duration, smoking and rheumatological comorbidity. Multiple imputation was used to replace missing values (5% for BMI).

Results

We included 728 patients, providing 2339 patient-years of follow-up and 868 treatment episodes with anti-TNF; 130 (17.9%) patients were obese. Obesity was associated with female sex (67% vs 54%), smoking (36% vs 22%), older age (median 42 vs 36 years) and prior exposure to methotrexate (25% vs 15%). In patients receiving ADA, obesity was significantly and independently associated with a higher risk of immunogenicity (Figure 1a, aHR: 2.15, 95%CI: 1.10 – 4.19) and treatment failure (Figure 2a), although significance of the latter association was lost after correcting for relevant confounders (aHR: 1.33, 95%CI: 0.87 – 2.03). In patients treated with IFX, obesity was not associated with immunogenicity (Figure 1b, aHR: 1.05, 95%CI: 0.54 – 2.03) or treatment failure (Figure 2b, aHR: 0.98, 95%CI: 0.70 – 1.39). Trough levels were significantly lower in obese patients treated with ADA, but not IFX.

Conclusion

In patients treated with ADA, but not IFX, obesity is associated with immunogenicity and possibly a higher risk of treatment failure. Proactive therapeutic drug monitoring may be warranted in obese patients treated with ADA. 

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