Journal of Crohn's & colitis最新文献

Background and aims: Inflammatory Bowel Disease (IBD) are known to impact patients 'sexual lives. The aim of this study is to create and validate a sexual QoL designed for youth with IBD.

Methods: This study was conducted in two phases: development of the score and validation of the items. A multidisciplinary team created a score called BLOOMI, based on two validated scores: the International Index of Erectile Function (IIEF) and the Sexual Function Questionnaire 28 (SFQ28). It was validated through a French multicentric cross-sectional study among patients aged 15-25 years with IBD by comparison with IIEF and SFQ28 gold standard scores.

Results: BLOOMI is a sexual QoL designed with 10 items and formatted as a disk. The score was validated through the participation of 104 patients with a median age of 23.2 years. BLOOMI was well correlated with both goldstandards and had a strong internal consistency. 19.1% of IIEF-responders have erectile dysfunction and median scores for the SFQ domains Desire, Arousal sensation and cognition, and orgasm are below the threshold for the absence of sexual dysfunction. Fatigue, abdominal pain, body image concerns or fear of anal leakages are correlated to a poorer sexual QoL.

Conclusions: BLOOMI score is a new validated score to assess the sexual QoL in 15-25 years with IBD. This tool may improve the screening for sexual challenges encountered by youths with IBD and may support future research into the impact of IBD on young patients' lives.

Background and aims: Sphingosine 1-phosphate receptor modulators have been associated with an increased risk of macular edema. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator.

Methods: We report the proportions and incidence rates [per 100 patient-years of exposure] of Macular edema and other ocular adverse events in the etrasimod clinical program, including patients with ulcerative colitis, Crohn's disease, eosinophilic esophagitis, alopecia areata and atopic dermatitis. Ulcerative colitis data were analyzed in two cohorts: Placebo-controlled ulcerative colitis and All ulcerative colitis [comprising the Placebo-controlled ulcerative colitis cohort plus open-label extension studies].

Results: In the Placebo-controlled ulcerative colitis cohort, Macular edema was reported in two patients receiving etrasimod [0.3%; incidence rate: 0.70] and one receiving placebo [0.3%; incidence rate: 0.84]. In the All ulcerative colitis cohort, one patient [0.1%; incidence rate: 0.13] receiving etrasimod reported two events of Cystoid macular edema. All events were non-serious, and one led to treatment discontinuation. No events of Macular edema were reported in other conditions. Nine and four patients receiving etrasimod reported Vision blurred and Visual impairment adverse events, respectively. All events were non-serious and most did not require any intervention.

Conclusions: Macular edema and other ocular events were uncommon in patients treated with etrasimod across multiple conditions. Incidence of Macular edema was comparable with placebo.

Background: HLADQA1*05 is recently associated with heightened immunogenicity to anti-TNF. Our aims were to determine whether HLADQ1*05 is a risk factor for primary non-response, loss of response (LOR) or adverse events (AE) to first-line anti-TNFα in patients with inflammatory bowel disease.

Methods: We performed a retrospective observational study enrolling biologic naïve patients with Crohn´s disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients.

Results: We enrolled 408 patients who started first-line infliximab (n=211) and adalimumab (n=197), with a mean follow-up of 7.6 years. Primary response at week 24 occurred in 347 (85.0%), LOR in 133 (38.3%) and AE in 93 (22.8%). The HLADQA1*05 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA1*05 was an independent risk factor for LOR (aHR=1.80, 95%CI=1.21-2.67) and immunogenicity (aOR=3.44, 95% CI=1.12-11.92). HLADQA1*03 was a protective factor against LOR (aHR=0.42, 95%CI=0.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA1*05 increased the risk of LOR to infliximab but not to adalimumab and HLADQA1*03 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab and the co-presentation of at least one allele of the HLADQA1*03 and HLADQA1*05 were risk factors for AE.

Conclusions: HLADQA1*05 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA1*03 seems to play a protective role against LOR, particularly to adalimumab. Female sex and infliximab are risk factors for AE.

Background: Exclusive enteral nutrition is an established treatment for active Crohn's disease (CD) but the role of partial enteral nutrition (PEN) in the broader management of the disease is less clear. This systematic review and meta-analysis reviewed the literature on the role of PEN in CD management.

Methods: This review was conducted following Cochrane recommendations. The protocol was registered on PROSPERO. Findings were reported following the PRISMA guidelines.

Results: Sixty-four articles were identified, of which 11 reported data from randomised control trials. Good quality evidence suggests that PEN may be used as a maintenance and induction therapy, particularly at high dosages and/or alongside exclusion diets. A higher dosage of PEN is associated with a lower risk of subsequent disease relapse, with benefits observed at intakes above 35% of energy requirements (35-50% PEN: OR [95% CI]: 0.42 [0.27-0.65]; >50% PEN: OR [95% CI]: 0.27 [0.08-0.88]). Low quality evidence suggests that post-operative use of PEN may prevent disease recurrence or enhance treatment outcomes when used as adjunct therapy to biologics. PEN can improve nutritional parameters, showing efficacy comparable to EEN in paediatric patients (weight: OR [95% CI]: -0.04 [-0.32, 0.25]). The effect of PEN on improving patients' quality of life is comparable to that of EEN and anti-TNFα therapies.

Conclusion: Partial enteral nutrition may help in various aspects of CD management but much of the current evidence is of low quality. Well-designed RCTs are required to confirm findings from current literature and before clinical recommendations can be made.

Background and aims: Emerging data indicate a stabilizing incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC), Crohn's disease (CD), and IBD unclassified (IBDU) in Western countries. We aimed to investigate the incidence of IBD, its initial clinical presentation, and patient-reported burden.

Methods: Copenhagen IBD Inception Cohort is a prospective, population-based cohort of patients with newly diagnosed IBD according to the ECCO guidelines in the period between May 2021 and May 2023, within a catchment area covering 20% of the Danish population.

Results: Based on 554 patients (UC: 308, CD: 201, and IBDU: 18), the incidence rates per 100,000 person-years were: IBD: 23.4 (95% confidence interval, 21.5-25.4), UC: 14.0 (12.6-15.6), CD: 8.6 (7.4-9.8), and IBDU: 0.8 (0.5-1.3). The median diagnostic delay was significantly shorter for UC (2.5 months (interquartile range [IQR] 1-6)) than for CD (5 months (IQR 1.5-11), p<0.01). Moderate-to-severe disability was reported by 34% of CD patients and 22% of UC patients (p=0.01), severe fatigue by 30% and 26% (p=0.43), and severely impaired health-related quality of life (HRQoL) by 43% and 30% of patients, respectively (p=0.01). Hospitalization rates (UC: 20%, CD: 34%, p<0.01), and need for immunomodulators, biologics, or surgery within three months of diagnosis, were high in both UC (3%, 7%, and 37%, respectively) and CD (31%, 18%, and 10%, respectively).

Conclusions: We found a high incidence of IBD in Copenhagen with a substantial disease burden characterized by early and high requirement for advanced therapies and high rates of fatigue, disability and impaired HRQoL at diagnosis.

Introduction: The Modified Multiplier of the SES-CD (MM-SES-CD) refines the assessment of endoscopic Crohn's Disease (CD) severity by differentially weighting parameters in the original SES-CD. A threshold of <22.5 for MM-SES-CD suggests endoscopic remission and correlates with a low risk of long-term disease progression. This study examines whether MM-SES-CD-defined endoscopic remission (ER) and response criteria are more sensitive to treatment effects compared to conventional SES-CD definitions.

Methods: This post-hoc analysis of the EXTEND trial compared various SES-CD and MM-SES-CD definitions of ER and endoscopic response in CD patients treated with adalimumab or placebo. The study included participants with moderate-severe CD and a baseline MM-SES-CD score ≥22.5. The primary outcome of ER, defined as MM-SES-CD <22.5, was evaluated at weeks 12 and 52. AUC analyses compared thresholds for predicting week 52 ER.

Results: Of the 100 participants (77.5% of the EXTEND population), 51 received adalimumab and 49 placebo. At week 12, 62% achieved MM-SES-CD ≥20% reduction from baseline, compared to 39% with SES-CD ≥50% reduction. At week 52, 56.9% of adalimumab-treated participants achieved MM-SES-CD <22.5, compared to 10.2% in the placebo group. MM-SES-CD ≥20% reduction at week 12 better predicted week 52 ER than SES-CD ≥50% reduction (AUC: 0.73 vs. 0.62, p=0.002).

Conclusion: MM-SES-CD definitions improved discrimination between treatment and placebo and offered superior predictive accuracy for week 52 ER. Its use may enhance trial efficiency and better predict long-term disease outcomes.

Background and aims: Fatigue is commonly observed in Crohn's disease (CD) and ulcerative colitis (UC), but its association to achieving remission is not clearly established. In this study we describe the odds for fatigue in patients with CD/UC one year after diagnosis based on different definitions of remission and identified factors associated with chronic fatigue (CF) among patients in endoscopic/radiological remission.

Methods: Patients ≥18 years with CD/UC were recruited from the IBSEN III cohort. Using the Fatigue Questionnaire, and dichotomizing the score, CF was defined as the presence of substantial fatigue (SF) for ≥6 months. Remission was divided into symptomatic (CD: HBI score<5/UC: SCCAI score<3), biochemical (faecal calprotectin ≤250µg/g), endoscopic/radiological (CD: normal intestinal MRI/CT combined with normal endoscopy/UC: Mayo endoscopic score 0) and histological (normal mucosal biopsies). Both the likelihood of SF/CF, depending on the definition of remission, and associations between CF and selected factors for CD/UC in endoscopic/radiological remission, were evaluated using binary logistic regression analysis.

Results: In total, 711/1416 patients were included. For both CD and UC, symptomatic remission significantly reduced the odds for SF and CF. Additionally, the odds for SF were significantly reduced for UC in biochemical remission. Among those in endoscopic/radiological remission (n=181), CF was independently associated with sleep disturbances (OR=10.40, 95%CI [3.28;32.99], p<0.001) and current treatment with infliximab (OR=4.31, 95%CI [1.15;16.17], p=0.03).

Conclusions: Stricter definitions of disease remission were not associated with a decreased likelihood of fatigue. For patients in endoscopic/radiological remission, CF was independently associated with sleep disturbances and current treatment with infliximab.

Background and aim: Only few studies have examined the socioeconomic consequences of being diagnosed with inflammatory bowel disease (IBD) in childhood or youth. Disease severity has been linked to lower earnings, but little attention has been paid to comorbid mental health conditions. The aim is to examine labour market participation (LMP) and income in patients with IBD-onset in childhood or youth and examine how disease severity and mental health conditions affects LMP.

Methods: In this register-based cohort study, we included patients with IBD-onset before 25 years of age and matched comparators. We estimated the relative risk (RR) of having low LMP and the median yearly income from ages 26 to 30. RR of low LMP was also assessed in subgroups of patients based on disease severity (severe/non-severe) and mental health conditions (yes/no).

Results: A total of 3,398 patients with IBD and 28,207 comparators were included. Overall, patients with IBD more often had low LMP (16.4% vs 14.4% in comparators), but slightly higher income (median yearly income difference at age 30: 1,141 Euro [95% CI: 483-1,798]). In subgroup analyses, only patients with severe IBD had higher risk of low LMP (RR 1.46 [95% CI 1.23-1.72]), not patients with non-severe IBD. Among patients with severe disease and mental health conditions 46% had low LMP (RR 5.03 [95% CI 4.38-5.78]).

Conclusion: Patients with IBD more often had low LMP, but their income was not affected. The subgroup of patients with severe disease and mental health conditions had the highest risk of low LMP.

Background and aims: Etrasimod is an oral, once daily, selective, sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This subgroup analysis evaluated the efficacy and safety of etrasimod 2 mg once daily vs placebo by prior biologic/Janus kinase inhibitor [bio/JAKi] exposure in ELEVATE UC 52 and ELEVATE UC 12.

Methods: Pre-defined efficacy endpoints were assessed at Weeks 12 and 52 in ELEVATE UC 52 and Week 12 in ELEVATE UC 12 in bio/JAKi-naïve and -experienced patients, and at Week 12 [pooled] based on prior advanced therapy exposure mechanism.

Results: In the ELEVATE UC 52 and ELEVATE UC 12 analysis populations, 80/274 [29.2%] and 74/222 [33.3%] patients receiving etrasimod and 42/135 [31.1%] and 38/112 [33.9%] patients receiving placebo, respectively, were bio/JAKi-experienced. In both bio/JAKi-naïve and -experienced patients, a significantly greater proportion receiving etrasimod vs placebo achieved clinical remission [p < 0.05] in ELEVATE UC 52 at Weeks 12 [naïve: 30.9% vs 9.7%; experienced: 17.5% vs 2.4%] and 52 [naïve: 36.6% vs 7.5%; experienced: 21.3% vs 4.8%]; in ELEVATE UC 12, this was observed only for bio/JAKi-naïve patients [naïve: 27.7% vs 16.2%, p = 0.033; experienced: 18.9% vs 13.2%, p = 0.349]. Similar patterns were observed for most efficacy endpoints. Among patients with prior anti-integrin exposure [N = 90], a significantly greater proportion achieved clinical response [54.1% vs 27.6%, p = 0.030], but not clinical remission [9.8% vs 3.4%, p = 0.248], with etrasimod vs placebo.

Conclusions: Bio/JAKi-naïve and -experienced patients had clinically meaningful induction and maintenance treatment benefits with etrasimod vs placebo.

Clinicaltrials.gov: NCT03945188; NCT03996369.