Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease.

BACKGROUND AND AIMS: Biological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level. MATERIAL AND METHODS: Patients with ulcerative colitis (UC) (n = 21) and Crohn's disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction. Results Of the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1). The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders. CONCLUSIONS: Mucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.

Sustaining the vitality of colonoscopy quality improvement programmes over time. Experience from the Norwegian Gastronet programme.

OBJECTIVE: An important challenge of any quality assurance (QA) programme is to maintain interest among participants to ensure high data quality over time. The primary aim of this study was to identify factors associated with endoscopist compliance with the Norwegian QA programme for colonoscopies (Gastronet). MATERIAL AND METHODS: The Gastronet registration tools are an endoscopy report form to be filled in directly after the procedure by the endoscopist, and a satisfaction questionnaire to be filled in by the patient on the day after the examination. During the study period from 1 January 2004 to 31 December 2006, endoscopist compliance was measured by assessing patient report coverage, defined as the percentage of patient satisfaction questionnaires received by the Gastronet secretariat divided by the total number of colonoscopy reports registered by the individual endoscopists during the study period. Multivariate logistic regression models were applied to identify individual factors related to patient report coverage. RESULTS: Eighty-eight endoscopists from 10 hospitals contributed a total of 16,149 colonoscopies. Overall patient report coverage decreased from 87% in 2004 to 80% in 2006. A low patient report coverage was associated with time since the registrations started [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.98; P < 0.001], use of sedation (OR 0.7, 95% CI 0.61-0.76; P < 0.001), and incomplete colonoscopy (OR 0.6, 95% CI 0.54-0.76; P < 0.001). CONCLUSIONS: Decreasing compliance with registration over time may compromise data quality and the validity of the results. Lower coverage of patient's reports (presumably for the most difficult examinations) may lead to erroneous conclusions regarding colonoscopy performance.

The Norwegian Gastronet project: Continuous quality improvement of colonoscopy in 14 Norwegian centres.

OBJECTIVE: The burden on colonoscopy capacity is considerable and expected to increase further as colorectal cancer screening programmes gain a foothold in Europe. In this situation, it is particularly important to evaluate the quality of the service given. In this article we present our first year of experience with a quality network of endoscopy centres in Norway (Gastronet). MATERIAL AND METHODS: A questionnaire focusing on caecal intubation rate and pain was completed by the endoscopist (on site) and patient (on the day after the examination). Fourteen centres participated with registration of 7370 colonoscopies by 73 endoscopists. RESULTS: There was 100% endoscopist participation, 87% coverage of colonoscopies and an estimated 76% questionnaire coverage of the patient population. Overall caecal intubation rate was 91%, range 83% to 97% between centres (p < 0.001). Patients reporting severe pain during colonoscopy differed from 2 to 24% between centres (p < 0.001). Variations could only partly be explained by differences in procedure practice (sedation, CO2 insufflation). For individual endoscopists, improvement after feedback on performance was restricted to the group of endoscopists having contributed with only 50-99 registered colonoscopies. CONCLUSIONS: In quality assurance programmes we recommend a limited number of variables for registration in order to secure high compliance by endoscopists and patients. One year of experience with Gastronet disclosed a satisfactory overall caecal intubation rate, but considerable variation between centres in practice and ability to offer painless colonoscopy. This suggests a need for formal, centralized training of colonoscopists or the development of quality standards for colonoscopy training and practice.