Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease.

Abstract

Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients. We retrospectively collected measurements of infliximab or adalimumab serum concentrations and anti-drug antibodies to identify anti-drug positive patients with loss response who were given an immunomodulator. Anti-drug antibodies against infliximab and adalimumab were detected in 98/376 (26%) and in 61/226 (27%) patients, respectively. Immunomodulators were given to 17/159 patients. Clinical response was recaptured in 6/10 patients receiving a thiopurine and in all (7/7) patients receiving methotrexate. In 7/8 patients on infliximab, serum concentrations increased (median 2.84 μg/mL; IQR: 1.19-4.98) and in 6/9 patients on adalimumab (median 3.10 μg/mL; IQR: 1.45-4.45). This was accompanied by a decrease in anti-drug antibodies to undetectable levels (median 11 months for both anti-TNF agents). In 23 patients, no immunomodulator was added but anti-TNF interval was shortened (17/23) or dosage was increased (6/23), which resulted in a clinical response in 10/17 and 2/6 patients, respectively. In 77% of IBD patients with loss of response due to immunogenicity, addition of immunomodulator resulted in undetectable anti-drug antibody levels, increased serum drug concentrations and regained clinical response. This strategy should be considered in this patient population before switching to other agents.