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* = Presenting author

DOP066 Disappearance of anti-drug antibodies to infliximab and adalimumab after addition of an immunomodulator in patients with inflammatory bowel disease

A. Strik*1, G. van den Brink1, C. Ponsioen1, R. Mathot2, M. Löwenberg1, G. D’Haens1

1Academic Medical Centre, Gastroenterology and Hepatology, Amsterdam, Netherlands, 2Academic Medical Centre (AMC), Hospital Pharmacy, Amsterdam, Netherlands

Background

Therapeutic options for patients with inflammatory bowel disease (IBD) who lose response to anti-TNF agents are limited. Loss of response, at least partly, is caused by anti-drug antibody (ADA) formation and subsequent neutralisation of the biologic effect. Addition of methotrexate (MTX) or thiopurines has been proposed to reduce ADA levels and thereby increasing serum drug concentrations. We performed a retrospective analysis to investigate the success rate of this strategy in IBD patients who lost response due to ADA formation.

Methods

In this cross-sectional study, all measurements (from September 2005 to September 2015) of infliximab (IFX) and adalimumab (ADL) serum concentrations and ADA serum levels in IBD patients collected at our centre were identified. Serum drug concentrations and ADA levels were measured with ELISA and radioimmunoassay respectively (Sanquin Laboratories, Amsterdam, The Netherlands). Patients were considered ADA positive if ADA levels were ≥ 12 AE/ml. In ADA positive patients, it was retrospectively determined if an immunomodulator (IM) was started in an attempt to reduce ADA and if this intervention had an effect on serum drug concentrations.

Results

We identified 602 IBD patients on anti-TNF therapy (83.7% Crohn’s disease; 16.3% ulcerative colitis). Available were 1 143 serum drug concentrations and 713 ADA level measurements were available. In 98/376 patients, ADA directed against IFX were positive, and in 61/226 patients ADA against ADL were detectable. In 118/159 ADA positive patients, anti-TNF therapy was immediately stopped, switched to another biological agent, or surgery was performed. In 17 patients, an IM was started because of loss of response owing to ADA formation. In 6/7 patients, addition of MTX resulted in undetectable ADA levels and subsequent increase in serum drug levels (median 3.2 μg/ml; IQR 0.8–4.1; p = 0.03). In 7/10 patients, ADA levels subsided after addition of a thiopurine, which resulted in increased serum drug levels in all 7 patients (median 1.4 μg/ml; IQR 0.5–3.0; p = 0.02). In 2 patients, addition of a thiopurine did not influence ADA levels and in one patient, the result of this intervention was unknown. Intensification of anti-TNF treatment by increasing the dose or decreasing the treatment interval, had a positive effect in 8/22 patients (36.4%), and increasing the dose of the IM in patients receiving combination therapy was successful in 2 out of the 2 patients.

Conclusion

Addition of an IM to IFX or ADL monotherapy in IBD patients developing ADA is a successful intervention in the majority of patients to decrease ADA levels and increase serum drug concentrations. Moreover, intensification of anti-TNF treatment may be beneficial.