Background Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination. Methods Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine. Results Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 – 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2). There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumab-treated patients after one or two doses of either vaccine. Antibody half-life was shorter in infliximab- than vedolizumab-treated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 – 4.1] vs 7.2 weeks [95% CI 6.8 – 7.6]) and ChAdOx1 nCoV-19 (5.3 weeks [95% CI 5.1 – 5.5] vs 9.3 weeks [95% CI 8.5 – 10.2], p value < 0.0001). Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3). Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 – 0.99], p = 0.035). Conclusion Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.
Background and Aims The simplified magnetic resonance enterography (MRE) index (sMARIA), London and “extended” London scoring systems are widely used in Crohn’s disease (CD) to assess disease activity, although validation studies have usually been single centre, retrospective and/or used few readers. Here, we evaluated these MRE indices within a prospective multicentre, multireader diagnostic accuracy trial. Methods A subset of participants (newly diagnosed or suspected of relapse) recruited to the METRIC trial with available terminal ileal (TI) biopsies was included. Using pre-specified thresholds, the sensitivity and specificity of sMARIA, London and “extended” London scores for active and severe (sMARIA) TI CD were calculated using different thresholds for the histological activity index (HAI). Results We studied 111 patients (median 29 years, interquartile range 21-41, 75 newly diagnosed, 36 suspected relapse) from 7 centres, of whom 22 had no active TI CD (HAI=0), 39 mild (HAI=1), 13 moderate (HAI=2), and 37 severe CD activity (HAI=3). In total, 26 radiologists prospectively scored MRE datasets as per their usual clinical practice. Sensitivity and specificity for active disease (HAI>0) were 83% (95% confidence interval 74-90%) and 41% (23-61%) for sMARIA, 76% (67-84%) and 64% (43-80%) for the London score, and 81% (72-88%) and 41% (23-61%) for the “extended” London score, respectively. The sMARIA had 84% (69-92%) sensitivity and 53% (41-64%) specificity for severe CD. Conclusions When tested at their proposed cut-offs in a real-world setting, sMARIA, London and “extended” London indices achieve high sensitivity for active TI disease against a histological reference standard, but specificity is low.
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.
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