S. McLaughlin

Use of a xanthine oxidase inhibitor in autoimmune hepatitis

A 62-year-old woman with type 1 autoimmune hepatitis (AIH) failed to sustain remission when steroids were withdrawn from a regimen of steroids and azathioprine (AZA). Thiopurine metabolites revealed elevated 6-MMP (6-methyl mercaptopurine) and low 6-TGN (6-thioguanine nucleotide) consistent with AZA-induced hepatotoxicity. Introducing the xanthine oxidase inhibitor allopurinol led to rapid normalization of alanine aminotransferase (ALT) and discontinuation of steroids.

Systematic review with meta-analysis: the management of chronic refractory pouchitis with an evidence-based treatment algorithm.

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis.

A multi‐centre audit of excess steroid use in 1176 patients with inflammatory bowel disease

Corticosteroids are central to inducing remission in inflammatory bowel disease (IBD) but are ineffective maintenance agents.

Letter: allopurinol co-therapy is safe and effective in autoimmune hepatitis

Al-Shamma, S McCrudden, R McLaughlin, S Letter England Aliment Pharmacol Ther. 2013 May;37(9):919. doi: 10.1111/apt.12285.

Sa1266 Low Dose Azathioprine and Allopurinol in Azathioprine Intolerant Patients: Is It Tolerated and Is It Effective in IBD?

Introduction Despite the advancement and introduction of new biological therapies, thiopurines remain effective treatment options for the maintenance of remission for both ulcerative colitis (UC) and Crohn’s disease (CD). Once tolerated and therapeutic, thiopurines have many advantages over biologics for long-term maintenance therapy. However, it has been documented that intolerance and adverse events are common. We have previously published our 36 month follow-up data reporting that 56.5% of our patients stop thiopurines due to side effects, abnormal liver function tests (LFTs) or therapeutic failure. Low dose azathioprine and allopurinol (LDAA) co-therapy is a well proven treatment option for patients who develop side effects or hepatotoxicity with standard dose azathioprine. LDAA has been used at our institution since 2010. Aim to report the safety, tolerability and therapeutic outcome at 12 months, for LDAA in patients who have failed standard dose azathioprine. Methods We maintain a prospective IBD data-base. After starting LDAA we monitor full blood count and LFTs weekly for 8 weeks. 6-Thioguanine (6-TGN) and 6-Methyl-mercaptopurine (6 MMPN) nucleotide levels are checked at 4–6 weeks. We searched our database for patients who started LDAA and had a minimum of 12 months follow-up. We recorded the indications for therapy, metabolite levels, and blood monitoring and clinical outcomes. Results 62 patients were started on LDAA. 25 (40%) were male. Mean age was 47 (range 16 – 77). Disease type was UC, 21; CD, 35; IBD(U), 6. Reasons intolerant to standard dose azathioprine were: drug side effects (nausea and arthralgia) 24; hepatitis (ALT 2x upper limit normal) 20; Hypermethylation (TGN: MMPN ratio >11), 12. Gout 4; High TPMT 2. At 12 months 44 (70%) remained on LDAA and were in clinical remission (HBI Of the remaining 18 (29%) patients, 3 (5%) were lost to follow up and 1 (2%) chose to stop LDAA. 1 patient (UC) required a colectomy. 3 (5%) stopped LDAA to conceive. 10/62 (16%) remained intolerant and treatment was stopped. One patient developed myelosuppression WCC Conclusion LDAA is well tolerated and effective in patients who failed standard dose azathioprine due to drug side effects and hepatotoxicity. This therapy results in resolution of hepatotoxicity and will allow more IBD patients to achieve clinical remission. Disclosure of Interest None Declared.

Su1224 Long Term Outcome of Azathioprine Therapy in 353 Consecutive IBD Patients

Introduction Thiopurines are the mainstay of therapy in Inflammatory Bowel Disease (IBD). Azathioprine (AZA) and Mercaptopurine are very effective at maintaining remission but have a wide range of side effects which can limit their use as long term maintenance therapy. To assess how effective AZA was in IBD, and what its limitations were, the outcome of 353 consecutive IBD patients started on AZA with at least onw year follow up was assessed. Methods Since 2005 all patients started on AZA for IBD have been recorded and monitored. These data were then used to assess the outcomes of patients where there had been at least one year of follow up. Outcomes recorded were whether AZA was still being taken or not. If still being taken information about the disease activity was recorded. If AZA therapy had been discontinued then the reason for this was recorded and subsequent therapeutic interventions noted. Results 353 patients had started AZA and had at least one year of follow up. TPMT status was checked in all patients. Dosing was as follows: low TPMT; 50mg and increased as tolerated. Normal TPMT; 2–2.5mg/kg. Of the 353 patients, 204 had Crohn’s disease (CD), 141 had Ulcerative Colitis and 8 had IBD-unclassified. The male:female ratio was 184:169 (52.1% male). Age range was 16–86 years (mean; 46). 322/353 (91%) remain under follow up. 127 (36%) of patients stopped taking AZA at one year. After six years 152 (43.1%) remained on AZA, 182 (51.6%) had stopped and in 19 (5%) the outcome was unknown. Nausea and myalgia were the main reasons for stopping AZA. 40(11.3%) patients developed hepatitis (ALT rise > 2xULN), 6 (1.7%) developed myelosuppression and 7 (2%) developed pancreatitis (consistent clinical presentation and raised amylase). Of the 182 patients who stopped AZA, 67 (37.8%) had an escalation of therapy – 20 started methotrexate, 18 started biologics and 29 underwent surgery. Of the 152 who continued AZA, 138 (90.8%) were in a clinical remission based on clinical assessment supported by normal C-reactive protein in 126 (91.3%), Harvey Bradshaw Index in those with CD 55 (40%) patients and endoscopic findings in 22 (15.9%). 112 (73.6%) patients had blood monitoring (FBC and LFTs) at least quarterly and 147 (96.7%) at bi-annually. Conclusion For such an important drug in IBD management a significant number of patients stop AZA due to side effects. This study highlights these so that patients can be accurately informed. It also highlights that AZA when tolerated is a very effective maintenance medication. Published data from our own and other units suggest that low-dose AZA in combination with allopurinol reduces side effects and increases tolerability and may make AZA a more effective longterm maintenance agent. Disclosure of Interest None Declared

Integrated systems for urine flow measurement: A critical review

Urine output is deemed very important by Physicians for diagnosis of many diseases like Acute Kidney Injury (AKI), Renal Replacement Therapy (RRT) etc. Until now, in hospitals, urine output is measured using a container having the measurement scale on it from which the nursing staff notes down the readings hourly. This is a very time consuming practice and may have adverse effect on the diagnosis process. In this paper, we first highlight the need of automated urine output measurement systems. Then, we critically evaluate the current systems developed for solving the automation problem of urine output measurement. Furthermore, we depict the concept of an integrated system for urine measurement and highlight the challenges that may be faced when developing a system for urine measurement. Finally, we give our suggestions for effective development of fully integrated system for automatic urine measurement.

P379 Is febuxostat the solution for patients who develop side effects to low dose azathioprine and allopurinol co-therapy?

Background: We and others have previously reported the utility of low dose azathioprine and allopurinol co-therapy in patients who develop side effects to standard dose azathioprine. This practice allows patients the convenience of continuing an oral drug and leads to health care savings by avoiding

OC-048 Filgotinib, a selective jak1 inhibitor, induces clinical remission and a reduction in pstat3 levels in patients with active crohn’s disease: results from the phase ii fitzroy study

Introduction Filgotinib (FIL), an oral, selective Janus kinase 1 (JAK1) inhibitor that blocks cytokine signalling by inhibiting STAT phosphorylation, which previously demonstrated efficacy in rheumatoid arthritis, is being evaluated in active Crohn’s disease (CD). Method 174 patients with moderate-to-severe CD and ulcerations confirmed by centrally read endoscopy were randomised 3:1 to 200u2009mg FIL or placebo (PBO) QD for 10 weeks. Thereafter, patients continued to receive FIL 200u2009mg, 100u2009mg or PBO QD for another 10 weeks. Immunosuppressive agents had to be discontinued, and steroid dosage was kept stable until Week 10 (W10). Key efficacy and safety data, and phosphorylation of STAT3 in intestinal biopsies from the 10u2009week induction period are presented. Results Mean baseline characteristics were similar between the FIL and PBO group. The primary endpoint (clinical remission CDAI <150 at W10) was met (FIL 47%, PBO 23%, p=0.0077). Significantly more FIL-patients showed clinical response (CDAI improvement ≥100 points) (FIL 59%, PBO 41%, p=0.0453) and improved quality of life (IBDQ mean changes from baseline) (FIL 33.8, PBO 17.6, p=0.0046) at W10. Numerically more FIL-patients had their CRP normalised (FIL 27%, PBO 14%) and showed at least 50% improvement in SES-CD score (FIL 25%, PBO 14%). Histopathology scores on biopsies at W10 decreased significantly more with FIL versus PBO (FIL −3.5, PBO: −0.6; p=0.0359). Filgotinib was well-tolerated; (S)AEs and early discontinuation rates were similar between groups. pSTAT3 levels were significantly reduced at W10 in FIL-patients (−36% (95%u2009CI: −51%, −17%)). However, in patients in clinical remission at W10, pSTAT3 levels were significantly reduced irrespective of treatment (PBO −62% (95%u2009CI: −83%, −16%) and FIL −42% (95%u2009CI: −57%,−21%)). In patients without clinical remission, pSTAT3 levels numerically decreased with FIL (−28% (95%u2009CI: −51%,+7%)) and not with PBO (+12% (95% CI:−21%,+94%). Conclusion Filgotinib is the first JAK inhibitor to demonstrate clinical efficacy in CD, as demonstrated by induction of clinical remission and response, and is associated with a significant reduction in pSTAT3 levels, suggesting that pSTAT3 behaves both as a pharmacodynamic marker for filgotinib and a disease activity marker. Disclosure of Interest S. Keshav Conflict with: Abbvie, ChemoCentryx, GSK, Merck, Conflict with: Abbvie, Allergan, Astra-Zeneca, Boehringer Ingelheim, ChemoCentryx, Dr Falk Pharma, Ferring, Gilead, GSK, Merck, Mitsubishi Tanabe Pharma, Pharmacosmos, Pfizer, Takeda, Vifor Pharma, J. Goh: None Declared, A. Hart: None Declared, S. Levison: None Declared, S. McLaughlin Conflict with: AbbVie, Conflict with: AbbVie, A. Van der Aa Conflict with: Galapagos NV, R. Galien Conflict with: Galapagos SASU, Y. Pan Conflict with: Gilead Sciences Inc, L. Meuleners Conflict with: Galapagos NV, C. Jamoul Conflict with: Galapagos NV, C. Tasset Conflict with: Galapagos NV, P. Harrison Conflict with: Galapagos NV, S. Vermeire Conflict with: AbbVie, Galapagos, MSD, Takeda, Conflict with: AbbVie, Galapagos, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer,Mundipharma, Hospira, Celgene, Second genome, Janssen, Conflict with: AbbVie

Mo1843 Introduction of an Inflammatory Bowel Disease Nurse Flexible Sigmoidoscopy Clinic Improves Patient Care by Initiating Earlier Treatment and Saves Clinic Slots

Introduction It is a marker of quality to be able to respond promptly and effectively to a patient with inflammatory bowel disease (IBD) at a time of flare. Many patients who contact the IBD helpline with flare symptoms require a flexible sigmoidoscopy (FS) for accurate assessment. These are usually performed on generic lists where follow up to consider a new treatment plan is arranged resulting in delays in treatment and creating pressure on clinic slots. An experienced IBD nurse prescriber (IBDN) was trained in FS with the aim to endoscopically assess patients and potentially start new treatment the same day. Aim Report the outcomes from the first 2 years of the IBD nurse endoscopist clinic Methods Records were reviewed of all patients attending the IBDN FS clinic. We evaluated the time from referral to FS, diagnoses, demographics and outcomes. Results 410 patients underwwent a FS with the IBDN 195 (47.6%) patients referred for rectal bleeding did not have IBD. 215 (52.4%) had a known diagnosis of IBD, 152 (70.7%) ulcerative colitis and 63 (29.35%) Crohn’s disease. 130 (60.5%) were female, mean age: 48 (range 16 – 88). Referral origin: 76 (35.3%) IBD Helpline. 58 (27%) IBD Consultant clinic. 39 (18.1%) IBDN Clinic. 27 (12.6%) Other medical clinic. 11 (5.1%) inpatient. 4 (1.9%) primary care. FS outcome: 55 (25.6%) commenced azathioprine, 47 (21.9%) started oral prednisolone, 38 (17.7%) commenced 5 ASA therapy, and 19 (8.8%) no changes to their care. In 41 (19.1%) FS was performed to assess need for or response to biological therapy. The 11 (5%) in-patients returned to the ward, 4 (1.9%) diagnosed with acute severe ulcerative colitis. Mean time from referral to test: 7 days, (range 0 – 28). In total 137 clinic slots were saved over 2 years, 76 direct from the helpline avoiding an urgent clinic slot. Following FS, 51 (23.7%) patients were discussed at the next IBD MDT, saving a follow up clinic slot. At the MDT the endoscopy findings were reviewed and discussed and appropriate treatment confirmed with the patient in the IBD telephone clinic. 10 (4.7%) patients were referred direct to the day unit to commence biological therapy following confirmation of active disease at FS as per the treatment plan from the Consultant referral. Conclusion The IBDN FS clinic reduced the time interval between developing symptoms and starting a new treatment plan in patients with IBD. The skilled prescribing IBD nurse endoscopist made changes in 91.2% at the time of the FS. The relatively small number of patients starting 5 ASA therapy suggests this had been optimised prior to FS suggesting patients attending the IBDN FS clinic had moderate to severe IBD. The introduction of the IBDN FS clinic also led to a reduction in demand on outpatient clinic slots. Disclosure of Interest H. Johnson: None Declared, S. Weaver: None Declared, S. McLaughlin Conflict with: Sponsored by Abbvie