IntroductionAcute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in ...large cohorts.AimsWe used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.MethodsAdults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019–1 June 2019 and 1 March 2020–30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids.Results37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission.ConclusionsIn a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed.Trial registration number NCT04411784.
Inflammatory bowel disease is characterized by significant interindividual heterogeneity. With a wider selection of pharmacologic and nonpharmacologic interventions available and in advanced ...developmental stages, a priority for the coming decade is to determine accurate methods of predicting treatment response and disease course. Precision medicine strategies will allow tailoring of preventative and therapeutic decisions to individual patient needs. In this review, we consider the future of precision medicine in inflammatory bowel disease. We discuss the critical need to extend from research focused on short-term symptomatic response to integrative multi-omic systems biology strategies to identify and validate biomarkers that underpin precision approaches. Crucially, the international community has collective responsibility to provide well-phenotyped and -curated longitudinal datasets for scientific discovery and validation. Research must also study broader aspects of the immune response, including components of the extracellular matrix, to better understand biological pathways initiating and perpetuating tissue fibrosis and longer-term disease complications.
Background
: In most areas of medical research, the label of 'quality' is associated with well-accepted standards. Whilst its interpretation in the field of medical education is contentious, there is ...agreement on the key elements required when reporting novel teaching strategies. We set out to assess if these features had been fulfilled by poster presentations at a major international medical education conference.
Methods
: Such posters were analysed in four key areas: reporting of theoretical underpinning, explanation of instructional design methods, descriptions of the resources needed for introduction, and the offering of materials to support dissemination.
Results
: Three hundred and twelve posters were reviewed with 170 suitable for analysis. Forty-one percent described their methods of instruction or innovation design. Thirty-three percent gave details of equipment, and 29% of studies described resources that may be required for delivering such an intervention. Further resources to support dissemination of their innovation were offered by 36%. Twenty-three percent described the theoretical underpinning or conceptual frameworks upon which their work was based.
Conclusions
: These findings suggest that posters presenting educational innovation are currently limited in what they offer to educators. Presenters should seek to enhance their reporting of these crucial aspects by employing existing published guidance, and organising committees may wish to consider explicitly requesting such information at the time of initial submission.
ObjectiveTo explore the ‘real world’ effectiveness of tacrolimus therapy for refractory ulcerative proctocolitis (UC).DesignRetrospective cohort study using prospectively collated clinical ...data.SettingA single district general hospital in Kent, UK. Clinical decisions and regular monitoring were undertaken by a single expert in inflammatory bowel disease.PatientsAll patients started on tacrolimus between January 2010 and August 2016 at Tunbridge Wells Hospital.InterventionsFollowing failure of conventional medication, tacrolimus was commenced at 0.5 mg/kg twice daily. Drug trough levels of 5–20 ng/mL were targeted. Other immunomodulation was stopped and steroids were weaned over 4–6 weeks.Main outcome measuresTreatment duration was measured for each patient. If the drug was stopped, the rationale, including specific side effects, was recorded. The patient’s subsequent management plan was noted.ResultsThirty-five patients were started on tacrolimus (range: 18–85, median: 36 years). Disease extent included proctitis to pancolitis. Twenty-five patients derived no benefit. Four patients responded, but drug side effects necessitated withdrawal. Eighteen of these 29 patients (62%) underwent surgery. One patient, who had previously responded, stopped the drug after becoming pregnant (healthy subsequent birth). Therefore, 5 of 35 patients (14%) remain on tacrolimus with sustained clinical response, ranging from 6 to 76 (median: 32) months of treatment. Treatment was most effective for proctosigmoiditis. There were no other demographic or biological markers for success.ConclusionsIn line with UK and European guidelines, tacrolimus can be beneficial for refractory UC. With appropriate monitoring, it appears treatment can be continued safely long term.
LINKED CONTENT
This article is linked to Saifuddin et al papers. To view these articles, visit https://doi.org/10.1111/apt.17223 and https://doi.org/10.1111/apt.17259
The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 ...vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs.
In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 Oxford-AstraZeneca, BNT162b2 Pfizer-BioNTech, or mRNA1273 Moderna) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing.
Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL geometric SD 5·7; p<0·0001), infliximab plus thiopurine (111·1 U/mL 5·7; p<0·0001), or tofacitinib (429·5 U/mL 3·1; p=0·0012) compared with controls (1578·3 U/mL 3·7). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL 4·3; p=0·74), ustekinumab (582·4 U/mL 4·6; p=0·11), or vedolizumab (954·0 U/mL 4·1; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations.
For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised.
Pfizer.
PDF
