ObjectiveAntitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.DesignAntibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.ResultsRates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001).ConclusionsInfliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration numberISRCTN45176516.
Summary
Background
Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid‐refractory acute severe colitis.
Aim
To determine the differences in outcome for acute severe ulcerative colitis between accelerated and standard‐dose infliximab
Methods
We collected data on hospitalised patients receiving differing regimens of rescue therapy for steroid‐refractory acute severe ulcerative colitis. Our primary outcome was 30‐day colectomy rate. Secondary outcomes were colectomy within index admission, and at 90 days and 12 months. We used propensity score analysis with optimal calliper matching using high risk covariates defined a priori to reduce potential provider selection bias.
Results
We included 131 patients receiving infliximab rescue therapy; 102 received standard induction and 29 received accelerated induction. In the unmatched cohort, there was no difference by type of induction in the 30‐day colectomy rates (18% vs 20%, P = .45), colectomy during index admission (13% vs 20%, P = .26) or overall colectomy (20% vs 24%, P = .38). In the propensity score‐matched cohort of 52 patients, 30‐day colectomy (57% vs 27%, P = .048) and index admission colectomy (53% vs 23%, P = .045) rates were higher in those receiving standard induction compared to accelerated induction but there was no difference in overall colectomy rates (57% vs 31%, P = .09). There was no significant difference in length of stay or in complication and infection rates.
Conclusion
In a propensity score‐matched cohort, steroid‐refractory acute severe ulcerative colitis patients, short‐term, but not long‐term, colectomy rates appear to be lower in those receiving an accelerated induction regimen.
South Asians with coeliac disease are less likely to present with 'irritable bowel syndrome' symptoms, but more likely to have features of vitamin D deficiency and iron deficiency, and have a higher alkaline phosphatase than white Caucasians. The differences in HLA alleles seen in South Asians with coeliac disease compared with white Caucasian patients suggests that among the South Asians, non-HLA regions may play a stronger role in disease susceptibility and presentation.
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