IBD prevalence in Lothian, Scotland, derived by capture-recapture methodology.

OBJECTIVE: IBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003. We aimed to establish the current, and project future, prevalence in Lothian, Scotland. DESIGN: We conducted an all-age multiparameter search strategy using inpatient IBD international classification of disease (ICD-10) coding (K50/51)(1997-2018), IBD pathology coding (1990-2018), primary and secondary care prescribing data (2009-2018) and a paediatric registry, (1997-2018) to identify 'possible' IBD cases up to 31/08/2018. Diagnoses were manually confirmed through electronic health record review as per Lennard-Jones/Porto criteria. Autoregressive integrated moving average (ARIMA) regression was applied to forecast prevalence to 01/08/2028. RESULTS: In total, 24 601 possible IBD cases were identified of which 10 499 were true positives. The point prevalence for IBD in Lothian on 31/08/2018 was 784/100 000 (UC 432/100 000, Crohn's disease 284/100 000 and IBD unclassified (IBDU) 68/100 000). Capture-recapture methods identified an additional 427 'missed' cases (95% CI 383 to 477) resulting in a 'true' prevalence of 832/100 000 (95% CI 827 to 837).Prevalence increased by 4.3% per year between 2008 and 2018 (95% CI +3.7 to +4.9%, p<0.0001). ARIMA modelling projected a point prevalence on 01/08/2028 of 1.02% (95% CI 0.97% to 1.07%) that will affect an estimated 1.53% (95% CI 1.37% to 1.69%) of those >80 years of age. CONCLUSIONS: We report a rigorously validated IBD cohort with all-age point prevalence on 31/08/2018 of 1 in 125, one of the highest worldwide.

Higher Adalimumab Drug Levels During Maintenance Therapy for Crohn's Disease Are Associated With Biologic Remission.

BACKGROUND: Adalimumab is an established treatment for Crohn's disease. Limited data are available regarding the relationship between adalimumab drug levels and serum/fecal markers of gut inflammation. We therefore aimed to characterize the relationship between adalimumab levels and biologic remission during maintenance therapy. METHODS: A single-center prospective cross-sectional study was undertaken on Crohn's disease patients who had received adalimumab therapy for a minimum of 12 weeks after induction. Data on clinical activity (Harvey-Bradshaw Index), C-reactive protein (CRP), adalimumab drug and antibody levels, and fecal calprotectin were collected. Biologic remission was defined as a CRP <5 mg/L and fecal calprotectin <250 µg/g. Adalimumab drug and antibody levels were processed using the Immundiagnostik monitor enzyme-linked immunosorbent assay. RESULTS: One hundred fifty-two patients had drug and antibody samples matched with CRP and fecal calprotectin. Patients in biologic remission had significantly higher adalimumab levels compared with others (12.0 µg/mL vs 8.0 µg/mL, P < 0.0001). Receiver operating characteristic curve analysis demonstrated an optimal adalimumab level of >8.5 µg/mL (sensitivity, 82.2%; specificity, 55.7%; likelihood ratio, 1.9) for predicting biologic remission. Multivariable logistic regression revealed that adalimumab levels >8.5 µg/mL were independently associated with biologic remission (odds ratio, 5.27; 95% confidence interval, 2.43-11.44; P < 0.0001). CONCLUSIONS: Higher adalimumab levels are associated with biologic remission. An optimal level of >8.5 µg/mL was identified.

Implementation of CT-P13 via a Managed Switch Programme in Crohn's Disease: 12-Month Real-World Outcomes.

BACKGROUND: Switching from Remicade to CT-P13 allows for significant cost savings and has been shown to be non-inferior to continued therapy with Remicade for the treatment of Crohn's disease. AIM: The aim of this work was to prospectively evaluate clinical outcomes in a cohort of patients with Crohn's disease switching from Remicade to CT-P13. METHODS: A prospective service evaluation was performed. The Harvey-Bradshaw index, CRP, faecal calprotectin and serum for infliximab/antibody levels were collected prior to patients' final Remicade infusion and at 6 and 12 months after switching to CT-P13 as part of routine clinical care. All adverse events during follow-up were also recorded. RESULTS: One hundred and ten patients on Remicade switched to CT-P13. No significant difference was observed between the Harvey-Bradshaw Index (p = 0.07), CRP (p = 0.13), faecal calprotectin (p = 0.25) or trough infliximab levels (p = 0.47) comparing before and at 6 and 12 months after the switch to CT-P13. Seven patients developed new infliximab antibodies after switching from Remicade to CT-P13. The majority of patients remained on CT-P13 at 12 months (84.5%) and the rate of adverse events and serious adverse events was 53.8 and 13.5 per 100 patient-years of follow-up, respectively. Switching to CT-P13 resulted in a cost saving of approximately 46.4%. CONCLUSION: The transition to CT-P13 from Remicade for the treatment of Crohn's disease is safe and has no negative effect on clinical outcomes at 12 months.

Use of methotrexate in refractory Crohn's disease: the Edinburgh experience.

BACKGROUND: In the two benchmark controlled trials in Crohn's disease (CD) supporting its use, methotrexate (MTX) was used as the immunosuppressant of choice in immunomodulatory-naive patients. However, in daily clinical practice MTX is used generally after thiopurine analogs have failed. METHODS: The data are reported using intramuscular (IM) MTX (25 mg/week) in the induction of remission and oral MTX (15 mg/week) in 39 CD patients with a median age of 32 years, assessed retrospectively. In all, 97% patients had failed azathioprine and/or mercaptopurine therapy due to lack of efficacy in 14 (36%) and side effects in 24 (61%) patients; 21 patients (53%) were steroid-dependent with a median dose of 27.5 mg prednisolone/day for over a year. RESULTS: In all, 72% of patients tolerated an induction regimen of 25 mg/week of IM MTX; 10% managed a reduced dose and 18% were intolerant. Remission was achieved in 71% of patients at 16 weeks. In the patients taking corticosteroids, withdrawal was achieved in 26% of patients and reduction in 47% at 16 weeks. Oral MTX therapy was continued in 22 patients after induction. In this group the probability of relapse was 78% at 50 weeks of oral therapy. CONCLUSIONS: Parenteral MTX therapy is efficacious in inducing remission in steroid-dependent CD patients, although its use is limited by side effects in approximately 30% of patients. Low-dose oral therapy does not maintain long-term remission and is not a suitable alternative.

Gastric fundic gland polyps in south-east Scotland: absence of adenomatous polyposis coli gene mutations and a strikingly low prevalence of Helicobacter pylori infection.

BACKGROUND AND AIM: Fundic gland polyps (FGP) were originally described in association with familial polyposis syndromes, but it is now accepted that the majority of FGP are picked up incidentally in up to 1.9% of routine endoscopies in dyspeptic patients. The familial adenomatous polyposis phenotype arises from germline mutations of the adenomatous polyposis coli (APC) gene. We aimed to see if there was any association between the presence of FGP, Helicobacter pylori, and two common APC gene mutations. METHODS: From a search of histopathology records in our unit, 85 consecutive patients were identified with a definite histological diagnosis of FGP between 1989 and 1997. Case notes could be retrieved in 48 cases to show the indication for endoscopy and endoscopic findings. Twenty-six patients (mean age 61 years, range 40-83 years) were tested for H. pylori status, and for the 1306 and 1061 bp deletions of the APC gene by the use of an enzyme-linked immunoassay and polymerase chain reaction techniques, respectively. RESULTS: Eighty-nine percent of patients underwent an endoscopy because of dyspepsia; 4.2% were anaemic, 4.2% had hematemesis and 1.2% had dysphagia. Only one patient was seropositive for H. pylori and no patient carried either APC gene deletion. CONCLUSIONS: This genetic information on those with FGP confirms previous phenotypic studies in that the majority of FGP are not associated with familial polyposis syndromes. The significance of such a strikingly low incidence of H. pylori infection in a dyspeptic population remains unclear.