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Background: Dosing of thiopurines [azathioprine (AZA) and mercaptopurine (MP)] in the management of IBD has been based upon patient weight. However, this appears unreliable in predicting final levels of thiopurine metabolites, leading to suboptimal clinical outcomes because of underand over-dosing, and ‘shunting' in 15% where toxic 6-methylmercaptopurine (6MMP) is preferentially produced over the efficacious 6-thioguianine nucleotides (6TGN), with 6MMP:6TGN ratio ≥20. Aims: 1. To determine prospectively the clinical value of timing of measurement of thiopurine metabolites during dose-escalating regimen of thiopurine initiation in a consecutive cohort of IBD patients being initiated on a thiopurine. 2. To determine if the 6MMP:6TGN ratio changes during thiopurine dose escalation. Methods: In this single centre, prospective, open label study patients were commenced on either a daily dose of 50mg AZA or 25mg MP (physician discretion). Doses increased fortnightly by 50mg for AZA or 25mg for MP until target was achieved, aiming for 2-2.5mg/kg for AZA and 1-1.5mg/kg for MP. Hematology, CRP and liver function tests were performed fortnightly to monitor toxicity. Thiopurine metabolites were measured fortnightly until steady-state was achieved, but results were not used for dosing decisions. Clinical and biochemical outcomes were recorded. Landmark analyses of shunter status used logistic regression models. Metabolite levels were analysed using linear regression models. Results: 64 patients (52 Crohn's, 11 ulcerative colitis and 1 IBD-U) were enrolled. Final metabolite outcomes were: 11 (17%) patients were shunters, 27 (42%) were underdosed (6TGN level of 450) and 21 (33%) were therapeutic. 6MMP:6TGN ratios escalated over time in shunters, but not in others. After 2 weeks of therapy, a 6MMP:6TGN ratio above 9 (p=0.058) was suggestive of shunting, while after 6 weeks, a ratio ≥12 (95% CI 7-28, p=0.01) was predictive of shunting. 6TGN levels at week 2 (median 106, range 0-328) predicted final 6TGN outcomes (median282, range 50-746, r=0.681, p .10). Conclusions: 6MMP:6TGN ratios increase during dose escalation in shunters only. Patients with a 6MMP:6TGN ratio 12 or above after 6 weeks should be considered for optimisation with allopurinol rather than waiting until 12 weeks of therapy. Weight-based dosing of thiopurines should no longer be used in standard practice.

Introduction Therapeutic drug monitoring (TDM) of infliximab (IFX) is useful in patients with Crohn’s disease (CD). Therapeutic cut-offs to predict active disease and the influence of thiopurines on drug levels (DL) according to 6-thioguanine nucleotide (TGN) are not defined. There is limited data on the utility of free anti-drug antibodies (ADAb) against total ADAb. We assessed the utility of TDM of IFX in CD using a commercially available ELISA and investigated the influence of TGNs on DL and free/total ADAb. Method Prospective evaluation of trough DL and ADAb using Lisa-Tracker, ((LT), Theradiag, France) and Immundiagnostik ELISA, ((IM), Germany) in 79 CD patients (male = 40) between January and May 2014. Only free ADAb is detected with LT assay, whereas IM assay measures total ADAb (semiquantitative). Total ADAb results were calculated using the cut off control. Results of TDM were assessed with respect to faecal calprotectin (FC), C-reactive protein (CRP) and clinical activity (Harvey Bradshaw Index, (HBI) Results Higher DL were observed amongst patients in remission (HBI 245 pmol/8 × 10 8 ) was not associated with ADAb (p = 0.5). TGN quartile analysis did not identify a value associated with DL (p > 0.5), nor was a therapeutic TGN associated with higher DL (p = 0.7). Conclusion IFX DL were inversely related to disease activity. A cut-off of 3.0–5.7 μg/mL was associated with active disease depending on the definition used. The presence of free ADAb was associated with active inflammation, whereas the presence of total ADAb was not. There was no relationship between TGN and DL or ADAb, although most patients were adequately dosed. This study highlights the limitations and utility of TDM in IBD. Disclosure of interest B. Warner: None Declared, M. Ward: None Declared, E. Johnston: None Declared, P. Irving Speaker Bureau of: AbbVie, MSD, Takeda, Warner Chilcott, Shire, Ferring and Tillotts Pharma.

Introduction Some, 1,2 but not all 3 studies have demonstrated a relationship between therapeutic drug monitoring (TDM) of adalimumab (ADA) and outcomes in inflammatory bowel disease (IBD). We evaluated the utility of TDM of ADA in patients with CD using two commercially available ELISA. Method ADA drug levels (DL) and anti-drug antibodies (ADAb) were measured in CD patients (n = 80) from 2 tertiary referral centres, between November 13 and February 14 using the Lisa-Tracker Duo ((LT) Theradiag, France) and Immundiagnostik ELISA ((IM) Germany). Faecal calprotectin (FC), C-reactive protein (CRP Results Neither assay showed a significant difference in ADA DL between remission and active disease (See table). No significant differences in DL were observed in TDM performed at trough (day 13/14, n = 13) or at any other time in the treatment cycle, nor amongst those receiving ADA every other week compared to weekly. Thiopurine metabolites (TGN) were performed in 51/52 patients taking thiopurines,(median 302, IQR 242–411 pmol/8×10 8 ). There was no significant difference between DL and TGN according to TGN quartiles. ADAb were detected in 1 (1.3%) patient using LT and 4 (5%) using IM. Concomitant immunomodulation or a therapeutic TGN (>235) did not significantly influence median DL or the detection of ADAb with either assay. IM ADA showed proportional positive bias (79.6%) against LT kit (Passing Bablok regression IM = 1.74 LT–0.06). Conclusion No optimal cut-off could be identified that predicted clinical or biochemical remission or FC. Concomitant immunomodulation and TGN concentration was not associated with higher ADA DL. ADAb development was very rare whether measuring free (LT) or total (IM) ADAb. Further studies are needed to establish the cause of DL variation and understand differences in ADA pharmacokinetics in patients with CD. Disclosure of interest E. Johnston: None Declared, M. Ward: None Declared, B. Warner: None Declared, P. Irving Speaker Bureau of: AbbVie, MSD, Takeda, Warner Chilcott, Shire, Ferring and Tillotts Pharma. References Mazor Y, et al . Aliment Pharmacol Ther. 2014;40:620–628 Roblin X, et al . Clin Gastro Hepatol. 2014;12:80–84 Chiu Y, et al . Inflamm Bowel Dis. 2013;19:1112–1122

Introduction Anti-TNF treatment is widely used in inflammatory bowel disease (IBD) but has been linked with reactivation of tuberculosis (TB). Screening for active and latent TB prior to initiation of anti-TNF therapy is therefore mandated. ECCO recommends interferon gamma release assays (IGRAs) as, unlike tuberculin skin test, positive tests are not caused by previous Bacillus Calmette–Guerin (BCG) vaccine. However, immunosuppressive agents can result in indeterminate or unreportable results[i] and there is no clear guidance on managing them. We quantified the prevalence of indeterminate or unreportable TB IGRA Elispot results in a large tertiary centre cohort of patients with IBD. Methods A single centre retrospective study of IGRA tests performed on IBD patients prior to commencement of anti-TNF therapy between Oct 2010 and Oct 2013. Results We included 140 patients (median age 34, range 24–86, 50% males). 92% had Crohn’s disease, 4% ulcerative colitis, and 4% IBD-unclassified. At the time of IGRA testing, 115 patients were on immunomodulators and 6 on prednisolone. 3 were positive for latent TB and were referred to infectious disease (ID) department prior to anti-TNF therapy. 3 had indeterminate results; all were on immunosuppressants (2=azathioprine, 1=methotrexate). 2 had a lymphocyte count 10 had unreportable results, 9 of whom were on azathioprine. On repeat testing, 4 were negative, and the remainder were still unreportable, one of whom had risk factors for TB and was treated with isoniazid chemoprophylaxis on the advice of the ID team. The remaining 5 patients started anti-TNF based on the absence of risk factors for TB. No patient had reactivation of latent TB at follow up (range 1–18 months). Lymphopaenia was found to be associated with non-reportable cases as compared to the reported cases (median lymphocyte count unreportable = 0.4, reportable = 1.2; p = 0.015). Conclusion Our results demonstrate TB IGRA is a useful test to screen for latent infection before initiating anti-TNF therapy. However, a minority of results are indeterminate or unreportable. In such cases repeat testing can produce definitive results. Low lymphocyte counts in association with immunosuppression may contribute to unreportable and indeterminate results; clinical risk stratification appears to be a safe way of managing such cases in this small cohort. Reference Papay P et al . Predictors of indeterminate IFN-γ release assay in screening for latent TB in inflammatory bowel diseases. Eur J Clin Invest. 2011 Disclosure of Interest None Declared.

regimens. Secondary endpoint was clinical remission at week 8 (Harvey-Bradshaw Index ≤4 in Crohn's disease (CD) or partial Mayo score ≤2 in Ulcerative Colitis (UC)). Results: Fifty-seven IBD patients (11 UC, 46 CD) were included in the study (group 0 n=29, group 1 n=17, group 2 n=11). Median time of infliximab drug-holiday before retreatment was 13 months (IQR 6-37.5). Median number of re-infusions was 6 (IQR 3.8-12.3). No significant differences were found among baseline characteristics of groups, with the exception of extraintestinal manifestations that were more frequent in the group 0 (p=0.03) and time of wash-out from the first infliximab treatment that was shorter in the group 2 (p=0.001). Fourteen patients (24%) presented an infusion reaction during infliximab retreatment; among them 11 subjects (19%) had a reaction during the second or the third re-infusion, and 10 patients (17%) discontinued infliximab due to severe re-infusion reaction. Group 1 presented significantly fewer re-infusion reactions in comparison with both groups 0 and 2 (1 versus 13, p=0.04). Also patients who maintained immunomodulators during infliximab drugholiday had significantly fewer re-infusion reactions in comparison with those without immunomodulators (1 versus 13, p=0.02). At multivariate analysis, only the maintenance with immunosuppressive agents during infliximab drug-holiday was independently associated with fewer re-infusion reactions (p=0.04). Thirty patients (53%) achieved clinical remission at week 8 with no significant differences among groups. Conclusion: Retreatment with infliximab may be effective in IBD patients; the induction regimen with 5 mg/kg at week 0-4-8 seems to be better tolerated, although only maintenance therapywith immunomodulators after discontinuation of the first course of infliximab therapy significantly reduced the occurrence of infusion reactions during retreatment.