Journal of Crohns & Colitis最新文献

Objective: We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment.

Methods: CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann-Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model.

Results: In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes.

Conclusion: Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration.

Background and aims: The highest reported incidence rate of inflammatory bowel disease [IBD], and especially of ulcerative colitis [UC], is found in the Faroe Islands. This study aimed to assess the incidence rate and temporal trends in prevalence over six decades.

Methods: All incident and prevalent patients diagnosed with IBD between 1960 and 2020 from the nationwide and population-based Faroese IBD cohort were included in this study. All patients fulfilled the Copenhagen Diagnostic Criteria.

Results: Overall, 873 individuals were diagnosed with IBD during the study period, 559 [64%] with UC, 151 [17%] with Crohn's disease, and 163 [19%] with IBD unclassified. A total of 59 patients had paediatric-onset IBD. The incidence of IBD continued to increase throughout the study period, as the age-standardized incidence rate started at 8 per 100 000 person-years [py] [European Standard Population, ESP] in 1960-79 and reached 70 by 2010-20. In 2021, the age-standardized period prevalence was 1414 per 100 000 persons. The IBD incidence was unevenly distributed among the islands with Sandoy having the highest rate of 106 per 100 000 py in 2010-2020.

Conclusions: The incidence of IBD continues to increase in the Faroe Islands, mainly driven by UC. The incidence shows an uneven geographical distribution, which suggests an adverse interaction between unknown environmental factors and genetic traits. The prevalence in 2021 corresponded to 1.3% of the Faroese population. Environmental risk factors are suspected to impact this homogeneous high-risk population; however, the reason for this is unclear.

Aim: To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation.

Methods: Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI <10, no steroids ≥4 weeks].

Results: Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively).

Conclusion: The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.

Background and aims: Poor sleep is prevalent in inflammatory bowel disease [IBD] and is associated with increased symptom severity and decreased quality of life. To date, research is mostly cross-sectional, limiting the ability to examine the causal direction between sleep and IBD symptoms. This short report aims to assess the temporal associations among sleep quality, pain, fatigue, and physical activity in adults with IBD.

Methods: Adult IBD patients [N = 18] completed a structured electronic diary two times per day [morning and evening] over 14 consecutive days. Morning diary items assessed sleep [sleep quality, wake after sleep onset, number of awakenings] and evening diary items assessed daytime IBD symptoms [abdominal pain, fatigue]. An actigraph measured daily step count [physical activity]. Generalised estimating equation models evaluated the lagged temporal associations between sleep ratings and next day pain, fatigue, and physical activity as well as reverse lagged temporal associations between daytime symptoms and physical activity and subsequent sleep ratings.

Results: Poor self-reported sleep quality predicted increased next day abdominal pain and fatigue scores. Increased time awake during the night predicted decreased next day physical activity. In the reverse analyses, only the relationship between daytime abdominal pain and wake after sleep onset was significant.

Conclusions: Poor sleep appears to drive IBD-related outcomes, such as pain and fatigue. These findings are a first step in demonstrating the key role of sleep in the IBD patient experience, potentially resulting in a treatment target for intervention. Future research is needed to confirm results in a larger sample.

Background and aim: Pan-enteric capsule endoscopy [PCE] is a highly sensitive but time-consuming tool for detecting pathology. Artificial intelligence [AI] algorithms might offer a possibility to assist in the review and reduce the analysis time of PCE. This study examines the agreement between PCE assessments aided by AI technology and standard evaluations, in patients suspected of Crohn's disease [CD].

Method: PCEs from a prospective, blinded, multicentre study, including patients suspected of CD, were processed by the deep learning solution AXARO® [Augmented Endoscopy, Paris, France]. Based on the image output, two observers classified the patient's PCE as normal or suggestive of CD, ulcerative colitis, or cancer. The primary outcome was per-patient sensitivities and specificities for detecting CD and inflammatory bowel disease [IBD]. Complete reading of PCE served as the reference standard.

Results: A total of 131 patients' PCEs were analysed, with a median recording time of 303 min. The AXARO® framework reduced output to a median of 470 images [2.1%] per patient, and the pooled median review time was 3.2 min per patient. For detecting CD, the observers had a sensitivity of 96% and 92% and a specificity of 93% and 90%, respectively. For the detection of IBD, both observers had a sensitivity of 97% and had a specificity of 91% and 90%, respectively. The negative predictive value was 95% for CD and 97% for IBD.

Conclusions: Using the AXARO® framework reduced the initial review time substantially while maintaining high diagnostic accuracy-suggesting its use as a rapid tool to rule out IBD in PCEs of patients suspected of Crohn's disease.

Background and aims: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis.

Methods: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation.

Results: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration.

Conclusions: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

Background and aims: Maintenance treatment for ulcerative colitis may be discontinued for multiple reasons. This post hoc analysis assessed the efficacy and safety of re-treatment with filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, in the phase 2b/3 SELECTION trial and its long-term extension [LTE] study in ulcerative colitis.

Methods: Partial Mayo Clinic Score [pMCS] response and remission were evaluated in patients who received induction with filgotinib 200 mg [FIL200] or 100 mg [FIL100], were randomized to treatment withdrawal [placebo] during maintenance, and following disease worsening, were re-treated with open-label FIL200 in the LTE study. Factors were evaluated for association with pMCS remission at LTE week 12, and safety outcomes were reported.

Results: Analyses included 86 patients [FIL200: n = 51; FIL100: n = 35]. Median time to disease worsening following treatment withdrawal was 15.1 weeks (95% confidence interval [CI]: 9.1-18.7) for FIL200-induced patients and 9.6 weeks [95% CI: 6.3-12.0] for FIL100-induced patients. Three-quarters [75%] of patients achieved a pMCS response within 4-5 weeks of re-treatment in both groups. At LTE week 48, pMCS remission was achieved by 45.1% and 51.4% of FIL200- and FIL100-induced patients, respectively. Factors independently associated with restoring efficacy included no concomitant use of corticosteroids at induction baseline, and high albumin levels, pMCS remission, and endoscopic score at maintenance baseline. No new safety signals were reported among re-treated patients.

Conclusions: In induction responders, re-treatment with FIL200 following temporary withdrawal from therapy restores response and/or remission in the majority of patients within 12 weeks. Re-treatment is well-tolerated. ClinicalTrials.gov identifiers: NCT02914522, NCT02914535.

Background: The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis.

Methods: A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome.

Results: Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a 'healthier' pouch microbiota, were observed following treatment with FMT.

Conclusion: The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.

Background: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited.

Aims: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD.

Methods: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors.

Results: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them.

Conclusion: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.