P513 Managing IBD patients on adalimumab based on trough levels and antibodies
Parisi I., Atherton R., McCartney S., Vega R., Mehta S., Whitley L., Kabir M., Kiparissi F., Bloom S.
University College London Hospital, Department of Gastroenterology, London, United Kingdom
Adalimumab (ADA) is a subcutaneous agent which blocks TNFα and has proven its efficacy in inducing and maintaining remission in IBD patients. Measuring ADA trough levels and identifying development of antibodies against ADA (AAA) may predict loss of response and alter medical management, however the optimal time of measurement and the most appropriate clinical decisions are yet to be defined. The aim of this study was to associate the time of measurement of ADA/AAA levels with results and to assess management based on these findings, particularly in association with AAA levels.
All IBD patients who had at least one measurement of ADA/AAA levels (ELISA) during their follow up in UCLH since January 2014 were included in the study. Patients' demographics, previous treatment, laboratory, endoscopic and imaging findings were recorded. Patients were divided in four categories using a previously described optimal cutoff of ADA levels at 4.9mcg/mL; those with satisfactory levels and presence or absence of AAA respectively and those with low levels and either positive or negative AAA. AAA titer was recorded both as complete count and in a centile.
71 IBD patients (63 Crohn's) were included. 40 (56%) had ADA/AAA measured due to clinically active disease, 29 (41%) as a routine check and 2 due to drug related side-effects. 42 (59%) were on a concomitant immunomodulator at the time of measurement. Median duration on ADA treatment was 2 years and 44% had weekly injections.
69 (97%) had detectable ADA levels. AAA were positive in 12 (17%) patients with a median titer of 42AU/mL. 70% had levels >4.9 and no AAA, 10% had low levels and no AAA, 10% had low levels and positive AAA and five patients had optimal ADA but positive AAA. As expected, ADA titer was significantly higher when AAA were negative (10.5mcg/mL vs 5.6mcg/mL, p=0.019). AAA positivity was associated with clinical relapse at measurement (n=9/12, 25%) as opposed to routine check of levels and no symptoms (7%, p=0.01). Interestingly, AAA presence was not associated with concomitant IM. Among patients with detectable antibodies, AAA titer in the 1st centile (0–5) was associated with preservation of optimal ADA levels >4.9 (p=0.013), while detectable ADA levels were maintained up to the 4th centile (0–75) of AAA (p=0.017). Of the 4 patients with optimal levels and positive AAA who had repeat measurement, two had undetectable antibodies with no specific intervention in the meantime.
Measurement of ADA/AAA on patients who experience loss of clinical response is more likely to identify patients with positive antibodies as opposed to routine check. Low AAA titer is associated with preserved ADA levels and should not necessarily prompt change in medical treatment.