Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study.

BACKGROUND: Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab. METHODS: Patients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn's disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery. RESULTS: We included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high. CONCLUSIONS: Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.

Variation in post-colonoscopy colorectal cancer across colonoscopy providers in English National Health Service: population based cohort study.

OBJECTIVES: To quantify post-colonoscopy colorectal cancer (PCCRC) rates in England by using recent World Endoscopy Organisation guidelines, compare incidence among colonoscopy providers, and explore associated factors that could benefit from quality improvement initiatives. DESIGN: Population based cohort study. SETTING: National Health Service in England between 2005 and 2013. POPULATION: All people undergoing colonoscopy and subsequently diagnosed as having colorectal cancer up to three years after their investigation (PCCRC-3yr). MAIN OUTCOME MEASURES: National trends in incidence of PCCRC (within 6-36 months of colonoscopy), univariable and multivariable analyses to explore factors associated with occurrence, and funnel plots to measure variation among providers. RESULTS: The overall unadjusted PCCRC-3yr rate was 7.4% (9317/126 152), which decreased from 9.0% in 2005 to 6.5% in 2013 (P<0.01). Rates were lower for colonoscopies performed under the NHS bowel cancer screening programme (593/16 640, 3.6%), while they were higher for those conducted by non-NHS providers (187/2009, 9.3%). Rates were higher in women, in older age groups, and in people with inflammatory bowel disease or diverticular disease, in those with higher comorbidity scores, and in people with previous cancers. Substantial variation in rates among colonoscopy providers remained after adjustment for case mix. CONCLUSIONS: Wide variation exists in PCCRC-3yr rates across NHS colonoscopy providers in England. The lowest incidence was seen in colonoscopies performed under the NHS bowel cancer screening programme. Quality improvement initiatives are needed to address this variation in rates and prevent colorectal cancer by enabling earlier diagnosis, removing premalignant polyps, and therefore improving outcomes.

Comparative effectiveness of antitumour necrosis factor agents and vedolizumab in ulcerative colitis.

INTRODUCTION: Antitumour necrosis factor (TNF) agents and vedolizumab are used to treat ulcerative colitis (UC) but the response is variable and there is little data on comparative effectiveness. Apart from previous exposure to anti-TNF agents, predictors of response have not been identified. We aimed to (i) compare the efficacy of anti-TNF agents and vedolizumab in UC and (ii) investigate the utility of clinical and biochemical parameters in predicting response. PATIENTS AND METHODS: Patients commencing any biological therapy for ambulant UC were included. Disease activity was monitored serially with the Simple Clinical Colitis Activity Index for up to 12 months. We compared the efficacy of anti-TNF agents and vedolizumab for induction and maintenance of response and remission on an intention-to-treat basis. We examined the utility of faecal calprotectin (FC) and early normalization of FC to predict response. RESULTS: Ninety-seven patients commencing anti-TNF and 42 commencing vedolizumab therapy were included. Vedolizumab-treated patients had significantly greater previous anti-TNF therapy exposure and a lower baseline FC. Response, remission and steroid-free remission rates were comparable between both groups at 6 weeks, 6 and 12 months. Clinical remission but not steroid-free remission at 12 months was higher in the vedolizumab group. There was a significant reduction in the Simple Clinical Colitis Activity Index and FC at 6 weeks, 6 and 12 months compared with baseline in both groups. Baseline FC and early normalization did not predict response at 6 and 12 months. CONCLUSION: The efficacy of anti-TNF and vedolizumab in UC appear comparable. We could not identify any predictors of response and remission.

Colonoscopic perforations in the English National Health Service Bowel Cancer Screening Programme.

BACKGROUND: Perforation is the most serious adverse event associated with colonoscopy. In this study of data from the English National Health Service Bowel Cancer Screening Programme, we aimed to describe the presentation and management of perforations, and to determine factors associated with poorer outcomes post-perforation. METHODS: The medical records of patients with a perforation following the national screening colonoscopy were retrospectively examined. All colonoscopies performed from 02/08/2006 to 13/03/2014 were studied. Bowel Cancer Screening Centres across England were contacted and asked to complete a detailed dataset relating to perforation presentation, management, and outcome. RESULTS: 263 129 colonoscopies were analyzed, and the rate of perforation was 0.06 %. Complete data were reviewed for 117 perforations: 70.1 % of perforations (82/117) occurred during therapeutic colonoscopies; 54.9 % (62/113) of patients with perforations who were admitted to hospital and in whom data were complete underwent surgery; 26.1 % (30/115) of hospitalized patients left the hospital with a stoma and 19.1 % (22/115) developed post-perforation morbidity. Perforations not detected during colonoscopy were significantly more likely to require surgery (P = 0.03). Diagnostic perforations were significantly more likely to require surgery (P = 0.002) and were associated with higher rates of post-perforation morbidity (P = 0.01). At presentation, the presence of abdominal pain (P = 0.01), a pulse rate > 100 beats per minute (P = 0.049), and a respiratory rate > 20 breaths per minute (P = 0.01) were significantly associated with the patient having surgery. CONCLUSIONS: This is the largest retrospective observational case series in Europe to describe post-perforation presentation, management, and outcomes. We have confirmed that perforation leads to surgical intervention, stoma formation, and post-perforation morbidity. Perforations not recognized during the colonoscopy were significantly more likely to require surgery. Diagnostic perforations were at greater risk of requiring surgery and developing post-perforation morbidity.

Post-polypectomy bleeding in the English National Health Service Bowel Cancer Screening Programme.

Background and study aims Colonoscopic polypectomy reduces colorectal cancer incidence, but is associated with complications including post-polypectomy bleeding (PPB). PPB ranges in severity from minor to life-threatening, making interpretation and comparison difficult. No previous studies have examined PPB rate according to a standardized severity grading system. We aimed to determine the PPB rate stratified by severity grading, explore factors that contribute to PPB severity grading, and describe PPB management. Methods Data relating to PPB were prospectively collected from all colonoscopies performed in one region of the English NHS Bowel Cancer Screening Programme (BCSP) from 06/12/2010 to 15/07/2014. PPB was defined and stratified into major, intermediate, and minor according to BCSP standardized definitions based on the American Society for Gastrointestinal Endoscopy adverse events lexicon. Results A total of 15 285 colonoscopies (23 766 polypectomies) were analyzed. The PPB rate per colonoscopy was 0.44 % (95 % confidence interval [CI] 0.34 - 0.54) and the rate per polypectomy was 0.29 % (95 %CI 0.20 - 0.38); 2.9 % of PPBs were major and 42.6 % were intermediate. Repeat endoscopy occurred in 27.9 % and was the most common reason for bleeding being categorized as of intermediate severity, although therapy was applied in only 36.8 % of these cases. A therapeutic intervention was significantly more common in patients with PPB who had either a hemoglobin drop ≥ 2 g/dL and/or a blood transfusion (P = 0.04, relative risk 3.47, 95 %CI 1.05 - 11.52). Conclusions This study specifically examined colonoscopic PPB rate, stratified using standardized criteria. The rates of PPB were low, with the majority of PPB being of minor severity. Current stratification of PPB severity combines measures of bleed severity with interventions. Using only hemoglobin drop ≥ 2 g/dL and/or blood transfusion as markers of PPB severity may simplify stratification, and allow a better assessment of the necessity and impact of an intervention.