Tailoring follow-up endoscopy in patients with severe oesophagitis.

Objective: We aimed to investigate the clinical utility of follow-up oesophagogastroduodenoscopy (OGD2) in patients with severe oesophagitis (Los Angeles grades C or D) through evaluating the yield of Barrett's oesophagus (BO), cancer, dysplasia and strictures. Second, we aimed to determine if the Clinical Frailty Scale (CFS) may be used to identify patients to undergo OGD2s. Design/method: Patients in NHS Lothian with an index OGD (OGD1) diagnosis of severe oesophagitis between 1 January 2014 and 31 December 2015 were identified. Univariate analysis identified factors associated with grade. Patients were stratified by frailty and a diagnosis of stricture, cancer, dysplasia and BO. Results: In total 964 patients were diagnosed with severe oesophagitis, 61.7% grade C and 38.3% grade D. The diagnostic yield of new pathology at OGD2 was 13.2% (n=51), new strictures (2.3%), dysplasia (0.5%), cancer (0.3%) and BO (10.1%). A total of 140 patients had clinical frailty (CFS score ≥5), 88.6% of which were deceased at review (median of 76 months). In total 16.4% of frail patients underwent OGD2s and five new pathologies were diagnosed, none of which were significantly associated with grade. Among non-frail patients at OGD2, BO was the only pathology more common (p=0.010) in patients with grade D. Rates of cancer, dysplasia and strictures did not vary significantly between grades. Conclusion: Our data demonstrate that OGD2s in patients with severe oesophagitis may be tailored according to clinical frailty and only be offered to non-frail patients. In non-frail patients OGD2s have similar pick-up rates of sinister pathology in both grades of severe oesophagitis.

Risk stratifying gastric ulcers: development and validation of a scoring system.

Objective: Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score. Design/method: All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated. Results: 778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3. Conclusion: Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.

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.