OWE-01 The effect of infliximab dose escalation in inflammatory bowel disease patients with antibodies to infliximab

Introduction Infliximab (IFX) dose escalation (DE) can be used in patients with inflammatory bowel disease with loss of response (LOR) or subtherapeutic drug levels. However, the long-term benefit of DE remains unclear, especially in those with antibodies to infliximab (ATI). Aim To assess the effect of DE in patients with ATI on drug level, clinical response and ATI status. Methods IFX and ATI trough levels (Immundiagnostik, UK) were measured at each IFX infusion in patients from May 2016 at a large referral centre and results retrospectively reviewed in December 2018. DE comprised a reduction in dose interval between maintenance infusions 10 mg/L is considered ‘positive’ by manufacturer. Positive ATI that resolved within two consecutive infusions were defined as transient. Results 78 patients were dose escalated (41 male; 40 CD; age 17–81; 51 on immunosuppression): 48 for LOR and 30 to optimise therapeutic drug monitoring levels. 73 received DE for a median 36 weeks (range 4–140). 5 patients stopped IFX after 1 further dose: 2 for LOR and 3 for infusion reaction (IR). At the time of DE, 31/78 (40%) patients had ATI >10 mg/L (ATI+). In patients with ATI ≤/>10 mg/L, DE significantly increased drug levels: median IFX levels of 1.3 and 0.9 respectively at baseline to 3.1 and 3.5 at week 24 (figure 1). After DE, 13/33 ATI+ had a fall in ATI ≤10 mg/L: median pre-DE ATI 23 mg/L (range 10–86), median post-DE ATI 9 mg/L. Pre-DE ATI levels in those without a fall in ATI ≤10 mg/L did not differ significantly from those where a fall was seen: median 65 mg/L (range 10–455). Acute IR following DE occurred in 3 patients with ATI >10 mg/L vs 0 in the transient/ATI- group (p=0.06). At week 24 following DE, 16/31 ATI+ patients were in clinical remission (10 recaptured after LOR; 6 maintained clinical remission) vs 30/47 ATI- patients (22 recaptured after LOR; 8 maintained clinical remission). Duration of clinical remission was shorter in ATI+ patients (median 24 weeks, range 0–88) than in those with transient/ATI- (median 36 weeks, range 0–126, p=0.06). Conclusions A strategy of DE for selected patients receiving IFX is associated with an increase in drug levels and a reduced rate of ATI positivity. This is associated with clinical remission in approximately 50% of patients at 6 months but the duration of this response is shorter in those with ATI >10 mg/L compared to those undergoing DE without ATI >10 mg/L.