A101 USTEKINUMAB LEVELS MEASURED DURING INDUCTION ARE ASSOCIATED WITH CLINICAL AND BIOCHEMICAL OUTCOMES AT WEEK 12 OF TREATMENT IN CROHN’S DISEASE

Abstract

Abstract Background Therapeutic drug monitoring (TDM) helps guide use of anti-TNF drugs in IBD patients. In addition, higher anti-TNF levels during induction therapy have been shown to be associated with better clinical and endoscopic outcomes. The role of TDM for more novel biologics such as ustekinumab (an anti- IL-12/23 antibody used to treat Crohn’s disease) remains to be elucidated. Aims We set out to investigate correlations between ustekinumab drug levels measured during induction with clinical and biochemical outcomes in patients with Crohn’s disease. Methods Patients with Crohn’s disease commencing treatment with ustekinumab were recruited from a single tertiary referral centre. Standard weight-based induction dosing was used. TDM was performed at week 2 and week 6 following IV induction dose. A drug-tolerant assay (Prometheus) was used. Kruskal-Wallis test was used to examine association between induction dose and ustekinumab levels. CDAI, CRP, and faecal calprotectin (FCP) were measured at week 12. Pearson correlation co-efficient was used to assess the relationship between ustekinumab levels and i)CDAI ii)CRP and iii)FCP at week 12. Results A total of 38 ustekinumab levels in 21 patients were measured. Week 2 ustekinumab levels were available for 17 patients, 16 (94.1%) of whom had levels of greater or equal to 25μg/mL. (1 patient had a level of 19.5μg/mL.) Week 6 ustekinumab levels were available for 21 patients; median 15μg/mL (IQR 9.9–21.3). No patients had detectable antibodies to ustekinumab. There was no significant association between absolute induction dose and week 6 ustekinumab levels; p=0.46. Of the 21 patients with week 6 levels, CDAI, CRP and FCP were available for 18, 18 and 16 patients respectively; Median CDAI 103(IQR 42–249), median CRP 2.3mg/L(IQR 1.0–11.3), median FCP 269μg/g(IQR109-932). There was a significant negative correlation between week 6 ustekinumab levels and CDAI; r=-.609, p=0.007. A negative correlation between week 6 ustekinumab levels and FCP was also significant; r=-.526, p=0.037. There was no significant correlation between week 6 ustekinumab levels and CRP; r=-.259, p=0.298. Conclusions We have demonstrated inter-patient variation in drug pharmacokinetics at week 6 following induction dose of ustekinumab in patients with Crohn’s disease. Drug levels at week 6 are significantly associated with clinical and biochemical markers of disease activity (CDAI, faecal calprotectin) at week 12. Measurement of week 6 ustekinumab levels may aid early identification of patients at risk of primary non-response to ustekinumab. Funding Agencies Testing provided by Prometheus