P527 Low adalimumab serum levels at Week 4 provoke immunogenicity and influence therapy outcome in anti-TNF naïve Crohn’s disease patients

Abstract

Background: Adalimumab (ADM) serum levels (SL) during maintenance are associated with treatment outcome and need for doseescalation in Crohn's disease (CD) patients. Little is known about the clinical relevance of proactive testing of ADM SL during induction. We evaluated correlation between ADM SL at Week 4, ADM anti-drug antibody (ADA) presence and outcome. Methods: Serum samples from biologically naive CD patients were prospectively collected at trough at Weeks 4 and 12 after ADM initiation. Clinical remission was defined as an average daily stool frequency < 0.001). Lower median SL at Week 4 were significantly associated with the presence of ADA at Week 12 (8.4 in ADA positive vs. 12.8 mug/ml in ADA negative patients, p = 0.006). Only 3 out of 15 ADA+ patients at Week 12, had detectable ADA at Week 4 already. Similarly, a trend towards lower median SL at Week 2 could be observed in these 3 ADA+ patients at Week 4, compared with the remaining ADA patients (4.4 vs. 9.9 mug/ml, p = 0.2). Although median weighted patient reported outcome, PRO2, significantly decreased from baseline to Week 12 (15.0 vs. 8.0, p < 0.001), SL at Week 4 were not significantly associated with clinical remission at Week 12. However, SL at Week 4 were associated with biological response and remission at Week 12 (p = 0.002, p = 0.005), and with the need for dose-escalation in symptomatic patients within the first year (p = 0.01). In patients given dose-escalation, discontinuation of ADM thereafter, due to loss-of-response (LOR), was associated with lower SL at Week 12 (p = 0.02) and ADA positivity at Week 12 (p = 0.001). Conclusions: Lower SL at Week 4 are associated with ADA development later on, and seem to be the cause rather than the consequence of lower SL afterwards. ADM SL during induction may predict the need for and the success of dose-escalation. Although these findings need prospective validation, availability of an ADM rapid assay creates the opportunity for optimising therapy early during induction.