Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.

BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109 /L) and faecal calprotectin (HR 2.95 for >50 µg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

Anti-TNF therapy for paediatric IBD: the Scottish national experience.

BACKGROUND AND AIMS: Biological agents are being increasingly used in the UK for paediatric-onset inflammatory bowel disease (PIBD) despite limited evidence and safety concerns. We evaluated effectiveness and safety in the clinical setting, highlighting drug cost pressures, using our national Scottish PIBD biological registry. METHODS: Complete usage of the biological agents, infliximab (IFX) and adalimumab (ADA) for treatment of PIBD (in those aged <18 years) from 1 January 2000 to 30 September 2010 was collated from all treatments administered within the Scottish Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) national managed service network (all regional PGHAN centres and paediatric units within their associated district general hospitals). RESULTS: 132 children had biological therapy; 24 required both agents; 114 had Crohn's disease (CD), 16 had ulcerative colitis (UC) and 2 had IBD Unclassified (IBDU). 127 children received IFX to induce remission; 61 entered remission, 49 had partial response and 17 had no response. 72 were given maintenance IFX and 23 required dose escalation. 18 had infusion reactions and 27 had adverse events (infections/other adverse events). 29 had ADA to induce remission (28 CD and 1 UC), 24 after IFX; 10 entered remission, 12 had partial response and 7 had no response. All had maintenance; 19 required dose escalation. 12 children overall required hospitalisation due to drug toxicity. No deaths occurred with either IFX or ADA. CONCLUSIONS: Complete accrual of the Scottish nationwide 'real-life' experience demonstrates moderate effectiveness of anti tumour necrosis factor agents in severe PIBD but duration of effect is limited; significant financial issues (drug cost-need for dose escalation and/or multiple biological usage) and safety issues exist.

Clinical progress in the two years following a course of exclusive enteral nutrition in 109 paediatric patients with Crohn's disease.

BACKGROUND: Exclusive enteral nutrition (EEN) is an effective first line treatment for active paediatric Crohn's disease (CD). AIM: To examine the effect of EEN on short- and long-term clinical outcome together with anthropometric measurements. METHODS: Retrospective case-note review in newly diagnosed CD (<16 years) who completed 8 weeks of EEN. Demographics, anthropometry, disease characteristics and inflammatory markers were collected at EEN initiation and at 1, 2, 6, 12 & 24 months post treatment initiation. EEN response was determined by a patient global assessment. RESULTS: One hundred and nine patients were included (Males 68; Median age: 11.2 years). After 8 weeks EEN, 65 were in remission, 32 improved and 12 had no improvement. By 4 weeks, mean weight/BMI z-score (s.d.) increased (P < 0.02) and between 4 and 8 weeks (P < 0.05). Baseline inflammatory markers all improved significantly by week 4 (albumin, CRP and platelets; all P < 0.01) and ESR (P < 0.00001). 63/109(58%) relapsed during follow-up. 44/63(70%) patients completed a second course of EEN with similar response rate, but lower weight gain (3.3 vs. 5.1 kg, P < 0.05). Height z-score did not change significantly over the 24 months. Introduction of azathioprine within 6 months of diagnosis did not improve height outcomes at 24 months. CONCLUSIONS: Weight and BMI z-score improved with EEN and changes are sustained to 2 years, but height z-score did not. Seventy per cent of patients who relapsed during 2-year follow-up managed a 2nd course of EEN. The optimal therapeutic strategies for length of EEN course and to improve linear growth are awaited.

Dietary and social characteristics of children with severe tooth decay.

BACKGROUND AND AIMS: Dental decay remains a major public health problem in Scottish children. The aim of this study was to investigate the relationship between diet, bowel habit, social class, and body mass index (BMI) in children with severe tooth decay. CHILDREN AND METHODS: A cross sectional study of 165 children aged 3 -11 years attending Glasgow Dental Hospital for extraction of teeth under dental general anaesthesia (DGA), was undertaken. A structured questionnaire was used to obtain information from each child on diet, bowel habit, and social status of their parents. Fibre and sugar scores were calculated from the frequency of consumption of a range of relevant foods. RESULTS: The children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An excess of children were from the most deprived parts of the city and they had the worst decay. Children with the worst decay were also significantly thinner. No relationship was found between tooth decay and bowel habit. CONCLUSIONS: In this selected group of children with poor dental health, those from deprived families were over-represented and had significantly more decay. Severe dental decay was also associated with underweight.