Introduction Infliximab (IFX) is an important agent in the treatment of inflammatory bowel disease (IBD). However, its use may be limited by the development of antibodies to infliximab (ATI). The aim of this study was to assess the timing and significance of ATI development in clinical practice. Method Since May 2016, all IBD patients receiving intravenous IFX for maintenance treatment, at a large, single, referral centre, have undergone therapeutic drug monitoring (TDM). Serum IFX trough levels and ATI were both measured by drug-tolerant enzyme-linked immunosorbent assays (Biohit, UK) from 199 patients at a variable interval following the start of IFX treatment. IFX trough levels were considered undetectable ( 7 mg/L). ATI were considered positive if >10 mg/L. Clinical remission was defined as a Harvey Bradshaw Index or Simple Colitis Activity Index≤4. Risk factors for ATI development were assessed by binary logistic regression model, using 522 sera taken from patients on maintenance therapy. Time to develop ATI, undetectable IFX levels and loss of response to treatment was assessed by Cox regression and Kaplan-Meier analysis. Results Male sex (OR=2.1; p Conclusion Although IS therapy protects against ATI formation, the risk of antibody development continues throughout treatment. If concomitant IS is aimed at reducing ATI formation, then this also needs to be continued for the duration of IFX therapy. Disclosure of Interest None Declared

Introduction Infliximab (IFX) is widely used for induction and maintenance of remission in inflammatory bowel disease (IBD). It has been suggested that monitoring drug levels and antibodies to infliximab (ATI) may allow treatment optimisation. The aim of this study was to examine the initial results, and their potential significance, from a programme of therapeutic drug monitoring (TDM), in a large, single, referral centre. Method Since May 2016, all IBD patients receiving intravenous IFX for maintenance treatment have undergone TDM. Serum IFX trough levels and ATI were measured by a drug tolerant enzyme-linked immunosorbent assays (Biohit, UK). IFX trough levels were considered as undetectable (<0.8 mg/L), low (0.8–2.9 mg/L), therapeutic: (3–7 mg/L) or supratherapeutic (>7 mg/L). ATI were considered positive if >10 mg/L. Clinical remission was defined as a Harvey Bradshaw Index or Simple Colitis Activity Index≤4. Results Initial screening of 162 maintenance patients (110 Crohn’s disease, 49 ulcerative colitis, 3 IBD-U; median age 36 years (16-82)), is shown in Table 1. Median duration of treatment was 88 weeks (range 12–581). 123/162 (76%) had drug levels that were undetectable (n=48) or low (n=75). Of these, 54/123 (44%) were ATI positive. 118/162 (73%) patients were in clinical remission, of whom 88/118 (75%) had low/undetectable drug levels while 35/44 (80%) patients with active disease had low/undetectable drug levels. Overall, 65 (40%) patients were ATI positive at initial screening. Positive ATI were associated with a lower level of IFX (median 1.4 vs 2.2 mg/L; p=<0.01, OR 2.97 (p<0.01) for undetectable levels). In those ATI positive, infusion reactions occurred in 3/180 (1.7%) infusions vs 0/342 in those ATI negative (OR of 11.49, p=0.03). Figure 1 shows the relationship between ATI status and IFX trough levels at initial TDM screening. Abstract PTH-088 Figure 1 Conclusion In an unscreened population, 17% of patients have undetectable drug levels and positive ATI, and therefore, may derive no benefit from continued treatment, although 61% of those were in clinical remission. The high overall prevalence of sub-therapeutic drug levels is important in planning strategies to optimise dosing in a clinic setting. Although ATI detected by this assay are associated with a low risk of infusion reactions, these were more common than when ATI were negative. Disclosure of Interest None Declared

Background: Infliximab is an anti TNFα antibody widely used in the treatment of inflammatory bowel disease. Accelerated infusion durations over 30–60 minutes, with reduced post infusion monitoring of 30–60 minutes have been shown to be safe and well tolerated in the originator molecule Remicade [1]. We previously audited 310 Remicade infusions in 103 patients and found that accelerated infusions were safe and that monitoring patients post-infusion was not necessary. Our unit started prescribing biosimilar infliximab Remsima in new starters in April 2016, and switched patients from Remicade from June 2016. The aim of this audit was to evaluate the safety of accelerated infusions of Remsima and the need for post-infusion monitoring. Methods: 276 Remsima infusions were administered to 154 patients during April to October 2016 (6 months). Data was recorded on completion of the infusion and post-infusion monitoring (PIM). Infusions were administered over 30, 60 or 120 minutes (Table 1). In patients switching from Remicade the first infusion was administered over at least 60 minutes. Patients receiving doses of 10mg/kg had their infusions administered over at least 60 minutes. In order to assess the need for PIM all patients were observed for 30 minutes following completion of the infusion. Blood pressure, pulse, respiratory rate, oxygen saturations were recorded every 30 minutes during the infusion and 30 minutes after completion of the infusion. Adverse reactions were classified as: Mild: no action required Severe: immediate action or treatment withdrawal A systolic drop in BP of ≥20mm/Hg was documented with details of action taken. Treatment of reaction and outcomes were recorded, including occurrence during infusion or post-infusion period. Details of any delayed reactions following discharge were obtained from patient notes. Results: During the infusion: 1 patient (0.36%) had a severe adverse reaction during the first Remsima infusion following a switch from Remicade. BP dropped ≥20mm/Hg during 19 infusions in 16 patients (range 22–50mm/Hg, median 24mm/Hg). No action was taken, all patients discharged following 30 minute post-infusion observation. Post-infusion monitoring: No adverse reactions were recorded during the PIM. 1 patient had a drop in systolic BP of 24mg/Hg. No action was taken. There were no patient self-reported adverse events post-discharge. Conclusions: Observed infusion reaction rate was 0.36% (2.91% infusion reaction in previous Remicade infusion audit). No adverse reactions occurred in the post-infusion monitoring period This audit suggests that accelerated infusions of Remsima are safe and well tolerated and post-infusion monitoring is unnecessary. References: [1] Donnelan CF. et al. (2009), Accelerated infliximab infusions are safe and well tolerated in patients with inflammatory bowel disease, Eur J Gastroenterology & Hepatology, 21(1)71–75

Introduction Infliximab is used in the treatment of inflammatory bowel disease. It is administered as an intravenous infusion over 2 h with a 2 h monitoring period. Accelerated infusions have been shown to be safe and well tolerated,1 reducing nursing time and increasing patient satisfaction.2 It has been suggested that post infusion monitoring may not be necessary,3 and it was our aim to establish this. Methods 310 infusions were administered to 103 patients over 6 months (January to July 2013). Infusions 1–4 were administered over 2 h with 2 h monitoring, 5–9 over 1 h with 1 h monitoring, and 10 onwards over 30 mins with no monitoring. A reaction was classified as mild if no action was required and severe if symptoms required immediate action or treatment withdrawal. A drop in systolic BP of ≥20 mm/Hg was recorded. Treatment of reaction and outcome were documented, including occurrence during or post infusion. Details of any delayed reactions post discharge were obtained from patient notes. Results Of 41 patients receiving infusions 1–4, 2 patients (4.87%) had an infusion reaction. One mild, and one severe. Both occurred during the first infusion. Both had previously been treated with infliximab. In 35 patients receiving infusions 5–9, 1 patient (2.86%) experienced a mild reaction during infusion 7, then a severe reaction during infusion 9. No infusion reactions were observed during infusions 10+ (122 infusions in 37 patients). 11 patients had infusions 10+ over 1–2 h due to side effects with accelerated infusions or 10 mg/kg dose. These patients were not monitored post infusion. One patient was hospitalised due to a delayed reaction one week after infusion 1 (previous infliximab treatment 108m). No side effects were observed during the infusion or monitoring period. No reactions were recorded during the monitoring period in any of the treatment groups. One patient had a drop in systolic BP (22 mg/Hg) during the monitoring period of their 5th infusion. No action was taken and the patient was discharged. Conclusion This audit has demonstrated that post infliximab monitoring is not necessary. We estimate that this would save 494 h of patient and nurse time per annum at our centre. References Donnellan CF, et al. Accelerated infliximab infusions are safe and well tolerated in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2009;21(1):71–75 Saxena P, et al. Safety and cost benefit of an accelerated infliximab infusion protocol in the treatment of ambulatory patients with inflammatory bowel diseases. Expert Opin Biol Ther 2013 Dec 21 [Epub ahead of print] Bhat S, et al. Are accelerated infliximab infusions safe in patients with inflammatory bowel disease? Inflammatory Bowel Disease 2010 Nov, 16 11;1922–5 Disclosure of Interest None Declared.

Introduction Mucosal CMV infection may complicate acute ulcerative colitis (UC), though the significance remains uncertain. The European Crohn’s and Colitis Organisation recommend tissue PCR or immunohistochemistry for CMV detection. The aim of this study was to review experience of assessing patients attending a single unit with acute UC for CMV infection. Methods A policy of biopsy for CMV infection was adopted for people with acute severe UC admitted to hospital (n = 37) or deteriorating symptoms as an out-patient (n = 8) from 2011–2013. Clinical severity was measured by Mayo score and endoscopic activity by Baron score. Biopsies were assessed for CMV viral DNA by realtime PCR. Serum IgG and IgM antibodies to CMV were measured by chemiluminescence. Results Biopsies were obtained from 45 patients with UC. 13/45 (28.9%) were positive for CMV DNA (median titre 34900; range 776–1540000 copies/ml). 9/13 (69.2%) CMV PCR positive (+) patients were steroid refractory compared to 14/32 (43.8%) CMV PCR negative (-) p = 0.12. Median Day 3 Mayo scores were 8 for the CMV+ group and 6 for the CMV- group (p = 0.59). Of IPs biopsied up to Day 1 of IV steroids (range -4–1), 6/22 were CMV+ and from Day 2 (median 6; 2–19), 5/20 were CMV+ (p = 0.96). Median cumulative steroid dose prior to biopsy was 0.28 g prednisolone equivalent for CMV+ patients and 0.39 g for CMV- patients (p = 0.51). 3/13 CMV+ patients had had prednisolone ≥10 mg/day for > 14 days prior to biopsy and 11/32 CMV- patients (p = 0.46). No biopsies contained typical histological features of CMV infection. Mayo and Baron scores did not differ between CMV+ and CMV- patients. Mucosal CMV DNA titre in CMV+ patients did not correlate with Baron or Mayo scores. Of the mucosal CMV+ patients, 8/8 tested (100%) were anti-CMV IgG positive with 0/7 IgM positive. Peripheral blood CMV PCR was positive in 10/13 in the biopsy PCR+ group and 0/7 in those biopsy PCR- (sensitivity 60%, specificity 100%). 12/13 CMV PCR+ patients were treated with ganciclovir. 11/13 (84.6%) achieved remission. 2/13 (15.3%) CMV+ and 2/32 (6.2%) CMV- required colectomy (p = 0.33). All 6 patients treated concomitantly with Infliximab and ganciclovir responded fully. Conclusion PCR of mucosal biopsies detects CMV infection due to viral reactivation in almost a third of patients with deteriorating or acute severe UC. No relationship was demonstrated between CMV infection and disease severity, response to treatment or prior steroid use. Treatment with anti-TNF agents was administered safely in combination with anti-viral drugs. Disclosure of Interest None Declared.

Background and Aims: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. Methods: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after >= 12months and follow-up of >= 6months. Investigations at assessment prior to cessation included >= 1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. Results: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50 mu g/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. Conclusion: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

Introduction Methotrexate (MTX) is used as an immunosuppressive treatment in inflammatory bowel disease (IBD). The aim of the study was to evaluate the long-term tolerability of MTX in adults with IBD from a large, single, tertiary referral centre. Methods IBD patients who had received MTX at a single centre between 2000 – 2011 were identified from the IBD service database and clinical records reviewed. Results 137 patients received MTX (Crohn’s Disease 105 (77%); ulcerative colitis (UC) 32 (23%)); mean age 44 (range 18–77). The median duration of MTX treatment was 13 months (range 1–127) with an initial dose of 25mg/week (range 10–25 mg) in 127/137 (93%) with 94% commencing MTX intramuscularly. The proportion who continued MTX for ≥ 3, 5, 10 years were 24% (33/137), 10% (14/137) and 1.5% (2/137) respectively. 89/137 (65%) discontinued MTX during the 11 year follow-up. The cessation rate due to lack of effectiveness was 17/137 (12%) by the end of the 2nd year of MTX, after which there were no further discontinuations for this reason. 77/137 (57%) reported ≥ 1 side-effect (SE) attributed to MTX, which was the commonest reason for discontinuing MTX (61/89; 69%). SEs leading to MTX cessation were most frequent during induction (defined as 0–3months): 22/61 (36%); followed by 3–12 months following initiation of MTX: 16/61 (26%). Specific SEs resulting in cessation during the 1st year of MTX were due to ≥ 1 of the following; 15 (40%) gastrointestinal (GI), 12 (32%) neurological (NS), 5 (13%) nonspecific malaise, 5 (13%) abnormal hepatic aminotransferase levels (2-fold increase up to or over the upper limit of normal), 2 (5%) hair loss, 5 other (1 each of sore throat, rash, infection, low platelets, injection site reaction). The incidence of discontinuation due to SEs in successive MTX years fell from commencement of MTX: 10/61 (16%) in the 2nd year, 5/61 (8%) in the 3rd year, 3/61 (5%) in the 4th year and 5 (8%) in total between the 5th-10th years. The most frequent SEs attributed to late discontinuation ( > 1year) were GI and NS. Over 11 years there were 12/137 (9%) reported cases of presumed MTX induced abnormal hepatic aminotransferase levels, of which 8 (67%) resulted in MTX cessation with biochemical resolution. Hepatotoxicity occurred during induction in 7/12 cases (58%) and was stopped in 5 of these (71%). In 5 patients with late abnormal hepatic aminotransferase levels, the median time to detection was 36 months (range 10–100months). MTX was discontinued in 3 of these. Conclusion In the largest single-centre experience to date, MTX in IBD is limited by high withdrawal rates with a 28% discontinuation rate due to SEs within the 1st year. Late hepatoxicity highlights the need for long term monitoring in maintenance therapy. Disclosure of Interest None Declared

Methods: For this survey we used a multicenter North-Holland cohort of 438 CD patients treated with ADA.Twenty-nine of these had previously been treated with IFX and received a second IFX treatment after failing ADA.Short-term and prolonged response to IFX was assessed retrospectively by reviewing clinical records.Results: 29 patients (62% luminal CD, 7% fistulising CD, 31% both) from 8 hospitals were included with complete follow-up data up to 18 months.IFX was re-started at 5 mg/kg in 20/39 (69%), 7.5 mg/kg in 1 patient and at 10 mg/kg in 8/29 (28%), at intervals varying between 4 and 8 weeks.Dose escalation was done in 8/29 (28%) of patients during retreatment with IFX.Twenty patients (69%) were on concomitant immune modulators at the re-introduction of IFX and 3 (10%) patients experienced adverse events: acute infusion reaction (n = 2, 7%) and delayed hypersensitivity reaction (n = 1, 3%).Clinical outcome is shown in Figure 1. Figure 1.Clinical outcome after re-introduction of infliximab.20/29 (69%) patients were still on continued Infliximab therapy after 18 months.Reasons for discontinuing the second Infliximab therapy included: non-response (n = 2, 7%), loss of response (n = 3, 10%), intolerance (n = 3, 10%) or non-compliance (n = 1, 3%).Conclusions: The majority of CD patients, failing prior treatment with IFX and ADA, benefit from re-introduction of Infliximab for at least 18 months.Only a small proportion of 9 patients failed on retreatment with IFX.Retreatment with Infliximab is to be considered a valuable strategy in this group of refractory CD patients.

Introduction The impact of stopping anti-TNF for patients in clinical and/or endoscopic remission in routine clinical practise setting is uncertain. We aimed to evaluate clinical outcomes in patients who discontinued anti-TNF electively across 3 units in the Yorkshire & Humber IBD Network, UK. Methods Crohn’s disease (CD) patients in whom anti-TNF (62 infliximab (IFX), 9 adalimumab (ADA)) was stopped electively following a planned assessment were included. All had been treated for ≥ 12 months and followed-up for ≥ 3 months following cessation of anti-TNF. Investigations at assessment prior to cessation included ≥ 1 of; colonoscopy, colon capsule (CC), small bowel capsule (SBC), magnetic resonance enterography (MRE), barium study (BS), CRP and clinical assessment (CA). Results Seventy-one patients (44 female; median age at diagnosis 24 years) were included with a median duration of IBD prior to anti-TNF of 24 (0–264) months. Indications were severe active luminal (50/71), fistulating perianal (18/71) and other fistulating disease (3/71). The median treatment duration was 18 months (range 12–78) with 62 (87%) on immunomodulators post anti-TNF withdrawal. Relapse rates within 90,180 and 365 days were 3/71(4.2%), 14/67(21%) and 27/57(47%) respectively. In perianal disease alone, the relapse rate was 6/18 (33%) at 1 year. 25 of those who relapsed were retreated with anti-TNF, with an overall recapture rate of 84%. In those retreated with the same agent as previously withdrawn the response rate was 80%. A further 5 were successfully retreated with ADA when IFX had been withdrawn. Those (6) who had a dose escalation in 6 months prior to withdrawal all relapsed. Assessment practise changed following NICE guidance in 2010. Prior to this 5/15(33%) stopping anti-TNF had a CA alone. Following NICE guidance 2/56 (3.6%) were assessed only by CA. Investigations to complement routine CA by Harvey Bradshaw Index (HBI), included ≥ 1 of colonoscopy (52), CC (4), MRE (19), SBC (5), BS (2) and CRP (66). HBI ≥ 4 and a CRP of ≥ 5 in the 6 months prior to formal assessment was observed in 26 patients. 14/26 (54%) relapsed following cessation of anti-TNF (positive predictive value of 61%). Further invasive investigations in this group were abnormal in 2 patients. Conclusion In this UK cohort, elective withdrawal of anti-TNF was associated with a relapse rate of 48% after 12 months, with a high retreatment response rate. Due to NICE guidance, increased invasive assessment occurred, but the role of endoscopy and imaging to evaluate remission prior to withdrawal of anti-TNF needs further evaluation. Disclosure of Interest A. Brooks: None Declared, S. Sebastian Conflict with: Dr Sebastian has participated in advisory boards and received speakers honoraria, educational and research grants from Abbott and MSD, K. Robinson: None Declared, L. Warren: None Declared, A. Wright: None Declared, A. Marsh: None Declared, H. Tsai Conflict with: Dr Tsai has participated in advisory boards and received speakers honoraria, educational and research grants from Abbott and MSD, F. Majeed: None Declared, M. McAlindon: None Declared, P. Hamlin Conflict with: Dr Hamlin has participated in advisory boards and received support for specialist nurses from Abbott and MSD, A. Lobo:None Declared

Introduction Infliximab (IFX) has demonstrated efficacy in moderate to severe ulcerative colitis (UC) with a reduction in short-term colectomy rates.1 In the UK, the National Institute for Health and Clinical Excellence (NICE) guidance relates to an induction course of three-doses for severely active ulcerative colitis.2 The aim of this study was to determine outcomes following IFX induction, including colectomy rate, use of corticosteroids (CS) or repeat IFX induction. Methods Patients with UC at a single large teaching centre received IFX induction for UC requiring hospitalisation or when urgent consideration of surgery was given for resistant or rapidly relapsing disease were retrospectively reviewed (2008–2011). All patients had a Simple Colitis Activity Index (SCAI) at 0, 2, 6 weeks. Results Twenty-seven patients were studied, median age 38 (range 23–64), with 17 (63%) refractory to oral or intravenous CS (13 and 4 respectively). All received CS in the year preceding IFX; median 1course (range 1–4). 23 (85%) were on immunosuppression (IS) (16 thiopurines, 7 methotrexate), 3 intolerant or non-responsive and 1 naïve to IS. Twenty (74%) received induction IFX alone. Median SCAI was 8 (range 4–13), 4 (range 0–9), 2 (range 0–10) at 0, 2 and 7 weeks respectively. Nine (45%) had a good clinical response, 6 (30%) had a partial response, and 5 (25%) had no response; median SCAI at end of induction 0, 4 and 7 respectively. Colectomy rate at 1 year post IFX induction by response was 2/9 (22%) with a good response, 3/6 (50%) with a partial response, 5/5 (100%) for no response, with partial or no response significantly more likely to result in colectomy compared a good response (p=0.02). Overall, the colectomy rate for induction IFX at 1 year was 0.50 (10/20; 0.30 in 1st 3 months, 0.20 in months 4–12). Seven (35%) required CS at a median of 3 months (range 0–5) and 25% (5/20) a 2nd induction course of IFX at a median of 4.5 months (range 2–25) post IFX induction. Of these 5, 2 (33%) had a colectomy, 1 is receiving maintenance IFX, 1 had 3rd induction with IFX, 1 had an infusion reaction and commenced adalimumab. Following initial IFX induction, a further 26% (7/27) received maintenance IFX infusions, median 3 (range 1–6). Of these, 1 receives maintenance IFX, 3 stopped due to lack of funding and are in remission, and 3 (43%) lost response-requiring colectomy. Conclusion Response to induction IFX determined by SCAI is useful in predicting colectomy in challenging UC patients with resistant or rapidly relapsing UC despite IS. Further induction or maintenance IFX is unlikely to result in remission with partial response on SCAI post induction IFX alone and in this group may be considered as a bridge to surgery. Competing interests None declared. References 1. Rutgeerts P, et al.N Engl J Med 2005;353:2462–76. 2. NICE Guidance 163, 2008.