BackgroundSequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4β7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting.MethodsPatients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period.ResultsSecond-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001).ConclusionCompared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Background Drug choice and order in Inflammatory Bowel Disease (IBD) is an important challenge and is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second line treatments in Ulcerative Colitis (UC). It is unclear if using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable outcome in UC in a real-world outpatient setting. Methods Patients with UC who were exposed to first-line anti-TNF (adalimumab/ADA or infliximab/IFX) or VDZ who subsequently switched to the alternate class between May 2013-August 2020 were identified following a review of databases at 10 hospitals. 88 VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were eligible. Data was collected retrospectively. Baseline demographics, disease activity indices, colectomy rates, treatment persistence and healthcare resource utilisation composite endpoint (HRUC) were examined over a 52 week period for the second line biologic. HRUC included unplanned emergency hospital attendance or hospital admission. The primary endpoints of 52 week treatment persistence, HRUC survival and colectomy free survival were analysed with Kaplan Meier method, statistical significance between the survival curves was assessed with Log Rank test. Propensity score matching (PSM) was applied to survival curves (tolerance level 0.1). For a subset where SCCAI scores available, week 52 corticosteroid free clinical response/remission rates were calculated (response: reduction of SCCAI ≥3 and remission: SCCAI ≤2).: Results The second line anti-TNF group had a significantly higher baseline endoscopic Mayo score (p=0.035) and lower concomitant immunomodulator use (p=0.001). Second line week 52 treatment persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF 15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC survival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33 (61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ 77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For treatment persistence and colectomy free survival statistical significance was maintained with PSM. Week 52 corticosteroid free clinical remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004 (Figure 4). Conclusion The VDZ second line cohort had significantly higher 52-week treatment persistence, lower HRUC and lower colectomy rates and higher corticosteroid free clinical remission rates. This data suggests that VDZ is an effective biologic in UC in a second line therapy after anti-TNF exposure. It highlights the effect of biologic sequencing on clinically important outcomes in an outpatient setting. Larger prospective studies are required to confirm these findings.

We present the case of an adult man with cardiofaciocutaneous syndrome, who initially presented to the emergency department with severe abdominal pain and distension, but was diagnosed with cardiac tamponade on CT after distended neck veins and tachycardia were identified on examination. He had emergency pericardial drainage to relieve the haemopericardium and was treated with colchicine. He was further found to be deficient in factors II, VII and X despite not being on warfarin, and was therefore supplemented with vitamin K. This confirms a diagnosis of vitamin K deficiency, likely multifactorial from malabsorption due to chronic intestinal pseudo-obstruction, small bowel obstruction and possibly exacerbated by subsequent ciprofloxacin use for small intestine bacterial overgrowth. This is the first report of spontaneous haemopericardium secondary to vitamin K deficiency in an adult patient not on anticoagulation, and is an important learning point due to the life-threatening progression of the haemopericardium and cardiac tamponade.

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