Abstract
Background
Upadacitinib (UPA) is a selective and reversible Janus kinase inhibitor.U-ACCOMPLISH is one of two phase 3 induction trials that evaluated the safety and efficacy of UPA 45 mg ...once daily (QD) in adults with ulcerative colitis (UC).
Methods
U-ACCOMPLISH was a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026) that enrolled patients with moderate-to-severe UC (defined as adapted Mayo score 5–9 with centrally read endoscopic score 2–3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Patients were randomized 2:1 to UPA 45 mg QD or placebo (PBO) for 8 weeks. At week 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA 45 mg QD for additional 8 weeks.The primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic– histologic evaluations from the 8-week PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.
Results
522 patients were randomized (UPA, n=345; PBO, n=177); the intent-to-treat population included 341 patients in UPA and 174 patients in PBO group. Baseline demographics and disease characteristics were similar between groups; 50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of patients receiving UPA 45 mg QD (33.5%) versus PBO (4.1%) achieved the primary endpoint (adjusted treatment difference: 29.0% 23.2, 34.7; P<0.001). A significantly higher proportion of patients receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001; Figure 1).Serious adverse events were reported by 3.2% and 4.5% of patients in UPA and PBO groups, respectively (Table 2). Similar rates of serious infection were observed in both groups (0.6%); 2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported in the study. One patient with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 patient with gastrointestinal perforation were reported in the placebo group.
Conclusion
In U-ACCOMPLISH, 8-week UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. The treatment was well tolerated, and the safety profile and AE prevalence was comparable with previous studies of UPA with no new safety signals identified.
P794 Fatigue in inflammatory bowel disease Schreiner, P; Rossel, J-B; Biedermann, L ...
Journal of Crohn's and colitis,
01/2019, Letnik:
13, Številka:
Supplement_1
Journal Article
Recenzirano
Odprti dostop
Abstract
Background
Fatigue is a common symptom of patients with chronic inflammatory diseases in general - and specifically in inflammatory bowel disease (IBD) - which results in huge impairment on ...quality of life of individuals. In spite of its frequency only few studies systematically investigated symptom burden and risk factors for fatigue in IBD. We aim to identify the prevalence of fatigue in a large IBD cohort and address physical risk factors, as well as psychological markers associated with fatigue.
Methods
We evaluated 1208 IBD patients from the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Significant fatigue was defined as a visual analogue scale (VAS-F, range 0–10) ≥4 and severe fatigue as a VAS ≥8. Impact of fatigue on daily activities was assessed by the Fatigue Severity Scale with a score > 3 defining relevant impairment. IBD-related factors were assessed through patient and physician questionnaires.
Results
Overall, 672 IBD patients (55.6%) reported fatigue (VAS-F ≥4), whereas only 133 (11%) reported severe fatigue. Fatigue was associated with female gender (women 65.8% vs. men 43.9%, p < 0.001) and initial IBD diagnosis (Crohn’s disease 59.1% vs. ulcerative colitis 51.5%, p = 0.008). Furthermore, patients with fatigue were of younger age (47.7 years vs. 51.4 years, p < 0.001), had a younger age at diagnosis (26.9 vs. 30.4 years, p = 0.001), lower educational level, higher disease activity indices and higher rates of complications, extraintestinal manifestation and intestinal surgery. Furthermore, patients suffering from fatigue had significantly higher indices for anxiety and depression in the Hospital Anxiety and Depression Scale and lower values in quality of life (IBD questionnaire). An impact of fatigue on daily activities was found in 49.5% of patients.
Conclusions
Fatigue is highly frequent in this large IBD cohort and impacts on daily activities. Patients at risk should be asked during outpatient visits about symptoms of fatigue and therapeutic strategies will need to be developed in the future.
Abstract
Background
Smoking cessation should be also recommended by all physicians in inflammatory bowel disease (IBD) as its worsens the course of disease in Crohn’s patients (CD), but is not a good ...option for ulcerative colitis (UC) patients, however rather protective, because of its extraintestinal deleterious effects. In our previous cross-sectional study, former smokers were older males with a higher body mass index (BMI) and CD patients with isolated ileal disease and UC patients with a less extensive disease were more likely to succeed in smoking cessation. We currently aimed to evaluate prospectively these findings.
Methods
Adult IBD patients were prospectively included in the Swiss IBD cohort from November 2006 to November 2015. They were asked about their smoking status at enrolment and during the follow-up (total of 2361 patients). We identified active smokers with a change of smoking status during follow-up suggesting a successful cessation of tobacco consumption and matched them to a group of patients continuing to smoke.
Results
2367 IBD patients (1368 CD, 999 UC) were included in the analysis. We identified 125 CD and 40 UC active smokers who ceased tobacco consumption during the follow-up. The most predictive factor for smoking cessation in CD patients was the involvement in a relationship (OR 1.9, p < 0.01), whereas it had no impact in UC patients. Gender, duration of illness, BMI, disease activity or location, stenosing or perforating complications and having surgeries were not predictive factors for cessation of tobacco.
Conclusions
Being in a relationship is a favourable factor for smoking cessation in CD patients. This result raised awareness on the importance of the role of the partner and possibly social network of our patients in the process. This should change our practice towards promoting the implication of the partner in this important decision
Abstract
Background
Smoking strongly affects the course of disease in patients with inflammatory bowel disease (IBD). Smoking is a risk factor for Crohn’s disease (CD) and worsens the course of the ...disease by increasing the rate of relapses, need for immunosuppressants and surgery. On the contrary, tobacco consumption is rather protective in ulcerative colitis (UC). Therefore, smoking cessation in CD leads to an early reduction of flares (in the first 3 months), a more benign course and less medical therapy.1,2 Our aim was to evaluate the effect of smoking cessation in UC and CD patients of the Swiss IBD Cohort study (SIBDCS).
Methods
Adult IBD patients were prospectively included in the Swiss IBD cohort from November 2006 to November 2015. They were asked about their smoking status at enrolment and during the follow-up. We identified active smokers with a change of smoking status during follow-up suggesting a successful cessation of tobacco consumption and matched them to a group of patients continuing to smoke,
Results
A total of 2367 IBD patients (1368 CD, 999 UC) were included in the analysis. We identified 125 CD and 40 UC active smokers ceasing tobacco consumption during the follow-up there were matched to 214 CD and 50 UC smokers for gender, age at diagnosis and age. Among CD patients, smoking cessation was protective against the progression to fistulising disease (OR = 2.2, p < 0.05), whereas, there was no association with increasing numbers of flares, stenosing behaviour or surgeries. Among UC patients, persistent smokers developed more extra-intestinal manifestations than quitters (OR = 2.4, p = 0.09), this was also present at lower level in CD (OR = 1.2).
Conclusions
Our findings in the Swiss IBD Cohort study are align with the literature: a reduction of the risk of fistulas among CD patients quitting smoking and the association between extraintestinal manifestations and aktive smoking status in IBD patients.3
References
1. Cosnes et al. Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology, 2011.
2. Nunes T, et al. Impact of smoking cessation on the clinical course of Crohn’s disease under current therapeutic algorithms: a multicenter prospective study. Am J Gastroenterol, 2016.
3. Severs M et al. Smoking is associates with extraintestinal manifestations in IBD. J Crohn Colitis, 2016.
Abstract
Background
Several studies demonstrate a lower diversity in the gut microbiota of patients with inflammatory bowel disease (IBD). Microbial alterations induced by dietary changes are amongst ...the key suspected responsible environmental factors to promote an increase in the incidence of IBD, and may adversely impact the course of established disease. Subsequent to our already presented results of lower psychosocial wellbeing in vegetarian diet (VD) and gluten-free diet (GFD) IBD patients (Poster 711, ECCO 2017) we investigated comparative microbial composition of IBD patients according to diet.
Methods
Dietary pattern was analysed in a total of 1656 IBD patients from the Swiss Inflammatory Bowel Disease Cohort Study between 2006 and 2015. Microbiota composition was analysed in 149 patients, including 12 vegetarian patients and 14 patients following a GFD by means of high-throughput sequencing. Within the majority of meat-eating patients, we further compared the microbiota of the low vs. high-meat-intake patients (i.e. ≤ 4 vs. >4 days per week).
Results
In the alpha diversity analysis (Shannon) we observed a significant difference between GFD and meat-eating Crohn’s disease (CD) patients with lower species richness in meat-eating patients (p = 0.026). In the ulcerative colitis (UC) group no significant difference in the alpha diversity was seen. Both CD and UC revealed significantly different β diversity in meat-eating patients compared with their VD and GFD counterparts. Bacterial taxa did not differ according to diet types in CD, whereas within meat-eating CD patients the following significant differences in taxa were found: Faecalibacterium, Bilophila and Butyricimonas taxa were found to be less abundant in the high-meat-intake CD group. On the other hand, there was a higher relative abundance of Eubacterium (family Erysipelotrichaceae), Enterococcum, Lactobacillus, Lactococcus, Fusobacterium, and Tepidimonas in the high-meat-intake CD group. In UC meat-eating patients there was a significantly higher relative abundance of Ruminococcus compared with GFD and VD patients. The high-meat-intake UC patients had a higher relative abundance of Lachnospira, Ruminococcus, and Parabacteroides.
Conclusions
The gut microbiota composition in meat-eating IBD patients is significantly different compared with those following a VD or GFD. The potentially anti-inflammatory taxa Faecalibacterium and Butyricimonas were reduced and the inflammatory taxa Erysipelotrichaceae and Enterococcus were increased in the high-meat-intake CD patients. Our results demonstrate several bacterial changes in regularly meat-eating IBD patients compared with VD or GFD, specifically lower species richness with a dose–response effect in meat-eating CD patients.
ECCO IBD Curriculum Lindsay, James O; Irving, Peter M; Mantzaris, Gerassimos J ...
Journal of Crohn's and colitis,
09/2017, Letnik:
11, Številka:
9
Journal Article
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