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P558. Antibodies against infliximab are associated with increased risk of anti-adalimumab antibody development in patients with inflammatory bowel disease

M.T. Frederiksen1, M.A. Ainsworth1, J. Brynskov1, O.Ø. Thomsen1, K. Bendtzen2, C. Steenholdt1, 1Herlev University Hospital, Department of Gastroenterology, Herlev, Denmark, 2Rigshospitalet, University Hospital of Copenhagen, Institute for Inflammation Research, Copenhagen, Denmark

Background

Infliximab (IFX) is effective for treatment of inflammatory bowel disease (IBD), but a notable proportion of patients relapse despite dose-optimization. In these patients, it is recommended to change to a second TNF-inhibitor such as adalimumab (ADL). However, there is considerable variation in the response to ADL after switching, and factors influencing outcomes are largely unknown. As development of anti-IFX antibodies (Abs) is a potential cause for IFX failure, we investigated if patients with anti-IFX Abs are prone to develop antibodies to ADL after switching therapy.

Methods

Observational, retrospective, single-center cohort study of all IBD patients treated with IFX or ADL (n = 482). Anti-IFX Abs, including cross-reactivity with ADL, anti-ADL Abs, and drug concentrations in serum were measured by clinically validated radioimmunoassay.

Results

Anti-IFX Abs were assessed in 189 patients (n = 131 Crohn's disease; n = 58 ulcerative colitis) treated with IFX as first line anti-TNF agent. Approximately half the patients (49%) were tested anti-IFX Ab positive (median 59 U/ml, IQR 26–97). Anti-IFX Abs appeared to be functional as they reduced the IFX serum levels of anti-IFX Ab positive patients: median 0.0 µg/ml, IQR 0–0 vs. 1.8 µg/ml, IQR 0.9–4.6 in anti-IFX Ab negative patients, p = 0.002. Anti-IFX Abs did not cross-react with ADL (n = 41 assessed). The treatment was changed to ADL in 66 patients with anti-IFX Abs and in 25 patients without anti-IFX Abs. Patients with previous anti-IFX Ab development were significantly more prone to develop anti-ADL Abs (10/29 patients: 34%) than those without previous anti-IFX Ab development (0/12 patients: 0%); OR estimated 13, p = 0.02. Detected anti-ADL Abs correlated with reduced blood levels of ADL in all cases: median 0.0 µg/ml, IQR 0–0 vs. 9.2 µg/ml, IQR 6.2–11.6 in anti-ADL Ab negative patients, p = 0.017.

Conclusion

Antibodies against IFX are highly drug specific and do not cross-react with ADL, thus making switching from IFX to ADL safe even in the presence of anti-IFX Abs. However, compared to patients without anti-IFX Abs, patients who develop anti-IFX Abs during previous IFX therapy have a higher risk of developing specific and functional anti-ADL Abs.