P706 Lower need for adalimumab dose intensification in IBD patients treated with combined immune suppression compared with adalimumab monotherapy

Abstract

Background: Combined immune suppression of anti‐tumour necrosis factor (anti‐TNF) biologicals and thiopurines or methotrexate has been considered to be superior to respective monotherapies in remission induction and maintenance of response in inflammatory bowel disease (IBD). For infliximab, a mutually positive pharmacokinetic effect of thiopurines on anti‐TNF levels and vice versa has been suggested to account for this clinical benefit. For adalimumab (ADA), the data are scarce and the clinical benefit of the combination therapy is questioned. Therefore, the aim of this study was to assess the impact of thiopurine concomitant medication on adalimumab pharmacokinetics. Methods: All IBD patients treated with ADA (HumiraR) in three IBD centres through August 2017 were eligible. ADA trough levels were routinely measured in all patients with maintenance ADA therapy using commercially available ELISA kit (RidascreenR, R‐Biopharm). All patients in remission were identified retrospectively from medical records. The proportion of patients who needed dose intensification was compared between the group of patients using thiopurines vs. patients on ADA monotherapy. The differences in the proportion of patients with low trough levels (below 5 μg/ml) between patients on ADA monotherapy vs. patients with azathioprine co‐medication were analysed statistically. Results: Out of a total of 241 IBD patients treated with ADA, there were 171 patients in clinical remission at the time of the first assessment of ADA trough levels. Out of these 171 patients, 23 patients (13.5%) had dose intensification to 40 mg s.c. every week based on clinical assessment of response to ADA. Among these 171 patients, 87patients (50.9%) were on ADA monotherapy and 84 patients (49.1 %) were using combined immune suppression. There was significantly lower proportion of patients with intensified adalimumab dose regimen among patients with thiopurines co‐medication (7 out of 84 patients, 8.3%) compared with adalimumab monotherapy (16 out of 87 patients, 18.4%), p = 0.043. There were 29 patients (16.9%) with levels of ADA below 5 μg/ml. There were no significant differences in the distribution of patients with adequate adalimumab levels between patients on ADA monotherapy compared with patients using co‐medication with thiopurines. Conclusions: To maintain adequate adalimumab levels, patients on adalimumab monotherapy need dose intensification more frequently than patients using combined immune suppression with thiopurines.