Published in:
01-06-2018 | Original Article
Interactions Between Thiopurine Metabolites, Adalimumab, and Antibodies Against Adalimumab in Previously Infliximab-Treated Patients with Inflammatory Bowel Disease
Published in: Digestive Diseases and Sciences | Issue 6/2018
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Background
Interactions between thiopurines and infliximab presumably contribute to superior effect of infliximab–thiopurine combination therapy in patients with inflammatory bowel disease (IBD). We examined whether principal cytotoxic thiopurine metabolites influence adalimumab (ADL) and anti-ADL antibodies (Abs).
Methods
Ninety-eight IBD patients previously treated with infliximab (96%) in whom trough ADL and anti-ADL Abs had been assessed as part of their clinical care were included. Thiopurine metabolites [6-thioguanine nucleotides (6-TGN) and methylated mercaptopurine metabolites (6-MeMP)] were determined at similar time points.
Results
ADL–thiopurine combination therapy was not associated with reduced anti-ADL Ab positivity compared to ADL monotherapy: 8/31 (26%) versus 19/67 (28%), p = 1.00. Concentrations of thiopurine metabolites were similar in anti-ADL Ab-positive and negative patients (6-TGN median 109 pmol/8 × 108 RBC vs. 112, p = 0.80; 6-MeMP 448 RBC vs. 720, p = 0.94). ADL trough levels did not differ between anti-ADL Ab-negative patients on ADL–thiopurine combination therapy and those on monotherapy (9.5 μg/mL vs. 7.6, p = 0.31). ADL levels were also comparable between patients on ADL mono- and combination therapy after stratification for 6-TGN/6-MeMP quartiles. There were no correlations between levels of 6-TGN and ADL (rP = − 0.17, p = 0.45; rS = − 0.38, p = 0.08), or 6-MeMP and ADL (rP = − 0.23, p = 0.31; rS = − 0.35, p = 0.11). Anti-ADL Ab positivity was associated with ADL treatment failure (OR 6 [2–20], p < 0.01). Higher trough ADL (9.6 μg/mL vs. 7.3, p < 0.05), but not concomitant thiopurine treatment, metabolite levels, or dosage, was associated with clinical remission.
Conclusion
Effectiveness of ADL therapy associated with circulating ADL levels and anti-ADL Ab formation. In this study, there appeared no direct interactions between thiopurine metabolites and ADL or anti-ADL Abs.