Abstract
Background
Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis UC. We sought to define the ...effectiveness and adverse effects of tofacitinib in a real-world cohort.
Methods
We conducted a retrospective observational cohort study of 134 patients with UC 64% male; median age 37 years range 16–81; 83% of patients had previously received at least one biologic treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index SCCAI or partial Mayo score PMS, depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3and SCCAI ≤2 or a PMS ≤1, respectively.
Results
Overall, 74% (88/119; 95 confidence interval CI 65–81% patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% 47/108; 95% CI 3453% patients at Week 26. Primary non-response was independently associated with younger age p = 0.014 and higher C-reactive protein CRP levels at baseline p = 0.004. Only 23% 3/13 of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% 27/134; 95% CI 1428% of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred.
Conclusions
In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.
Religiosity defines the extrinsic utilitarian and intrinsic spiritual motivations of religious individuals. Many people have adopted vice product consumption, including addictive behaviours like ...alcohol drinking and gambling, in part to relieve daily pressure and tension. By applying the Theory of Planned Behaviour, this exploratory study examines the role of religiosity on Chinese individuals' alcohol drinking and gambling consumption urges via the mediating role of perceived (internal and external) behavioural control. Two separate studies were conducted, with a total of 1,010 respondents. The results showed a significant direct positive relationship between intrinsic religiosity and an individual's perceived behavioural control (both internal and external). There was no significant link between extrinsic religiosity and perceived behavioural control. Moreover, perceived internal behavioural control partially mediated the relationship between intrinsic religiosity and vice product consumption urges. These findings have meaningful implications for policymakers and social marketers.
IntroductionA substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is ...labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring.Methods and analysisThe DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants.Ethics and disseminationMultisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment.Trial registration numberACTRN12622001458729.
Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease ...treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.
Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.
Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.
Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.
ISRCTN45176516.
Antitumour 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.
Antibody 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.
Rates 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).
Infliximab 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.
ISRCTN45176516.
LINKED CONTENT
This article is linked to Gordon et al and Mahmoud & Itzkowitz papers. To view these articles, visit https://doi.org/10.1111/apt.16155 and https://doi.org/10.1111/apt.16175
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