Nicola C. Hare

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease : analysis of nationwide experience in Scotland (2004-2008)

Background  Adalimumab is a second generation humanized anti‐tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn’s disease (CD).

Therapeutic options in acute severe ulcerative colitis

Ulcerative colitis is a relapsing–remitting inflammatory disease affecting the colon and is associated with considerable morbidity. In acute severe attacks, there continues to be an associated mortality rate of 1–2%, even in specialist units. During an acute severe exacerbation, approximately two-thirds of patients will respond to intravenous corticosteroid therapy, the accepted first-line therapy in such cases. For steroid-refractory patients, options are limited to surgery (colectomy) or second-line agents, such as ciclosporin or infliximab, used in an attempt to salvage the colon. Considerable debate exists over the optimal management of such patients. During the last decade, an increased understanding of the pathogenesis of inflammatory bowel disease has led to the rapid development of other biological agents, such as basiliximab and visilizumab. Novel methods, such as leucopheresis, have been studied and other established immunomodulatory agents, such as tacrolimus, have also been suggested. The purpose of this review is to highlight some of the areas of recent development in the treatment of acute severe ulcerative colitis and review important safety data, with a particular emphasis on biological agents.

Multiple sclerosis in the context of TNF blockade and inflammatory bowel disease

In August 1999, a 26-year-old Caucasian woman presented with abdominal pain, diarrhoea and weight loss. Active small bowel Crohns disease (CD) was diagnosed on barium follow-through and confirmed histologically following ileal resection in October 1999. Subsequent radiological and endoscopic investigations demonstrated extensive small bowel and foregut involvement with stricturing disease. Despite treatment with 6-mercaptopurine (6-MP) (1.25 mg/kg/day) and corticosteroids, control of disease activity was suboptimal and four further laparotomies were required. (or stricturoplasties and adhesiolysis). Between January and July 2004, she had received four infliximab (Remicade®, Schering-Plough) (5 mg/kg) infusions with limited efficacy. In June 2007 the humanized anti-tumour necrosis factor (TNF) agent, adalimumab (Humira®, Abbott Ltd.), was commenced (80 mg loading dose, then 40 mg every second week) with good clinical effect. In October 2007, she presented with ‘pins and needles’ affecting the fingertips of her left hand and the right side of her face. These symptoms evolved over 2 weeks to include parasthesias affecting her left arm and intermittent diplopia. Her left hand became clumsy and her left leg weak. In addition to adalimumab she was also treated with mercaptopurine, ketamine, gabapentin, esomeprazole, folic acid and loperamide. Her mother suffered from rheumatoid arthritis. Clinical examination revealed bilateral internuclear ophthalmoplegia with associated horizontal nystagmus. There was reduced sensation to light touch and pin prick in the left upper and lower limbs. There was mild pyramidal weakness on the left arm and leg with finger–nose ataxia, predominantly right-sided. Reflexes were brisk throughout and there was an upgoing left plantar response. She was afebrile and demonstrated no signs of sepsis. Haematological and biochemical parameters including full blood count, renal and thyroid function, vitamin B12, folate and C reactive protein were normal. Rheumatoid factor, anti-nuclear and anti-neutrophil cytoplasmic antibodies were negative. MRI scanning of the central nervous system (CNS) demonstrated a number of white matter lesions …

P349 Serum calprotectin: a novel biomarker to predict outcome in acute severe ulcerative colitis?

Reference(s) [1] Stephane Paul, Emilie Del Tedesco, Hubert Marotte, et al. (2013), Therapeutic Drug Monitoring of Infliximab and Mucosal Healing in Inflammatory Bowel Disease: A Prospective Study, Inflammatory Bowel Disease. [2] Filip Baert, Maja Noman, Severine Vermeire, et al. (2003), Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn’s Disease, The New England Journal of Medicine.

PTU-123 Acute severe ulcerative colitis: the last 12 years in Edinburgh

Introduction Acute severe ulcerative colitis (ASUC) remains a common reason for urgent colectomy, yet there are relatively few large cohort studies exploring prognosis and outcome.1–3 This study aims to examine presentation and management of ASUC in the Western General Hospital, a tertiary referral centre in Edinburgh and to identify prognostic factors. Methods Patients were identified from a large database of participants in genetic studies in Edinburgh, as well as from two previous small cohorts of ASUC studied in Edinburgh. More recent cases were found from minutes of a weekly IBD meeting. Cases were included if they met the standard clinical, radiological and pathological criteria for ulcerative colitis and required an admission for 3 days or more requiring intravenous corticosteroids and/or colectomy. Two cohorts were analysed, one with full clinical detail (97 admissions in 86 patients) and one with more basic detail (444 admissions in 323 patients). Results Overall colectomy rate was 31.8%. Haemoglobin, C reactive protein and albumin at days 0 and 3 were significant predictors of colectomy in both cohorts (p<0.05 in each case), while in the detailed cohort day 3 but not day 0 stool frequency was predictive (p<0.001 and 0.81 respectively). A simple score was derived to predict colectomy at admission based on disease extent, albumin and CRP. Scores of 0, 1, 2 and 3 corresponded to risks for colectomy of 10%, 31%, 61% and 75%. For day 3 parameters, both the Edinburgh acute colitis (Ho) score (Abstract PTU-123 figure 1) and Travis criteria performed well.Abstract PTU-123 Figure 1 Conclusion ASUC remains an important cause of colectomy. This study confirms the prognostic value of the Ho score and Travis criteria at day 3, but also indicates that day 0 CRP and albumin are strong predictors of outcome. Competing interests None declared. References 1. Dinesen LC, et al. J Crohns Colitis 2010;4:431–7. 2. Ho GT, et al. Aliment Pharmacol Ther 2004;19:1079–87. 3. Turner D, et al. Clin Gastroenterol Hepatol 2007;5:103–10.

PTH-082 Serum Calprotectin: A Novel Biomarker to Predict Outcome in Acute Severe Ulcerative Colitis?

Introduction Acute severe ulcerative colitis (ASUC) remains an important clinical problem and is associated with significant morbidity and requirement for colectomy. Faecal calprotectin and C-reactive protein (CRP) have previously been shown to predict the need for colectomy but there is an unmet need for further biomarkers. Serum calprotectin has not previously been analysed for this purpose and may provide a novel way of determining disease activity and outcome. The aim of this study was to assess how serum calprotectin relates to faecal calprotectin and other blood markers of inflammation, and to determine whether serum calprotectin on admission predicts colectomy. Methods Blood samples were collected prospectively from patients who presented with ASUC as defined by the Truelove and Witts criteria. Blood samples were taken within the first 24 hours of admission. Faecal samples were pre-processed using PhiCal™ extraction buffer. Samples were stored at –80°C and analysed in duplicate using the PhiCal™ calprotectin ELISA according to manufacturer’s instructions. Samples with a calprotectin result of > 2500 µg/g were diluted and retested. Statistical comparisons were made between serum calprotectin and other markers of inflammation using Spearman’s correlation coefficient, and ROC curve analysis was performed to determine how well each test performed in predicting colectomy. Results There were 45 patients recruited to the study with ASUC, of which 22 (49%) were female. Median age on admission was 40 years (interquartile range [IQR] 26–62). Median disease duration was 12 years (IQR 0–59). 26 of the 45 patients had a paired faecal sample for calprotectin analysis. There was no difference in sex, age or disease extent between those with or without faecal calprotectin. Serum calprotectin correlated significantly with CRP (R2 = 0.46, p < 0.0001) and with albumin (R2 = 0.12, p = 0.023) but not with faecal calprotectin (R2 = 0.02, p = 0.450). ROC analysis gave an AUC of 0.69 for serum calprotectin compared with 0.71 for CRP and 0.58 for faecal calprotectin. A cut off for serum calprotectin of 400 µg/g gave a sensitivity of 0.68 and a specificity of 0.69. Conclusion In the setting of acute severe ulcerative colitis, serum calprotectin is comparable with serum CRP in predicting outcome. Further work is needed to establish if it may be a useful predictor of outcome in patients with ulcerative colitis who fail to mount a high CRP response despite endoscopic assessment confirming severe active inflammation. Work is also ongoing to establish its utility in the outpatient setting both in Crohn’s disease and ulcerative colitis. Abstract PTH-082 Figure 1 Disclosure of Interest None Declared.

Sa1241 Acute Severe Ulcerative Colitis: the Last Twelve Years in Edinburgh

Background Acute severe ulcerative colitis (ASUC) remains a common reason for urgent colectomy, yet there are relatively few large cohort studies exploring prognosis and outcome. This study aims to examine presentation and management of ASUC in the Western General Hospital, a tertiary referral centre in Edinburgh, UK and to identify prognostic factors. Methods Patients were identified from a large database of participants in genetic studies in Edinburgh, as well as from two previous small cohorts of ASUC studied in Edinburgh. More recent cases were found from minutes of a weekly IBD meeting. Cases were included if they met the standard clinical, radiological and pathological criteria for ulcerative colitis and required an admission for 3 days or more requiring intravenous corticosteroids and/or colectomy. Two cohorts were analysed, one with full clinical detail (97 admissions in 86 patients) and one with more basic detail (444 admissions in 323 patients). Results Overall colectomy rate was 31.8%. Haemoglobin, C-reactive protein and albumin at days 0 and 3 were significant predictors of colectomy in both cohorts (p<0.05 in each case), while in the detailed cohort day 3 but not day 0 stool frequency was predictive (p<0.001 and 0.81 respectively). A simple score was derived to predict colectomy at admission based on disease extent, albumin and CRP. Scores of 0, 1, 2 and 3 corresponded to risks for colectomy of 10%, 31%, 61% and 75%. For day 3 parameters, both the Edinburgh acute colitis (Ho) score (figure 1) and Travis criteria performed well. Conclusions ASUC remains an important cause of colectomy. This study confirms the prognostic value of the Ho score and Travis criteria at day 3, but also indicates that day 0 CRP and albumin are strong predictors of outcome.