Tofacitinib for ulcerative colitis:results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice. Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Conclusion: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients

Prediagnostic Serum Vitamin D Levels and the Risk of Crohn’s Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study

Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings

Dietary patterns and risk of inflammatory bowel disease in Europe: Results from the EPIC study

Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium and the subsequent development of Crohn’s disease (CD) and ulcerative colitis (UC). Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n=110) or UC (n=244) during followup were matched with four controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI 0.32-1.19, p trend=0.19) and 0.63 (95% CI 0.28-1.42, p trend=0.23) for CD and 0.80 (95% CI 0.50-1.30, p trend=0.40) and 0.81 (95% CI 0.49-1.34, p trend=0.60) for UC. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI 0.49-1.47). Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect

Earlier discontinuation of TNF-α inhibitor therapy in female patients with inflammatory bowel disease is related to a greater risk of side effects

BACKGROUND: In rheumatoid arthritis and psoriasis female sex has been shown to be associated with discontinuation of anti-tumour necrosis factor-α (TNF-α) therapy. AIM: To retrospectively assess the association between sex and TNF-α drug persistence in patients with inflammatory bowel disease (IBD). METHODS: All IBD patients on anti-TNF-α therapy with a minimum follow-up of 12 months in a single tertiary centre were identified. Patient and treatment characteristics and reasons for anti-TNF-α discontinuation were recorded. Overall and cause-specific drug persistence was analysed with Kaplan-Meier followed by Cox proportional hazards regression models. RESULTS: We included 529 patients (49.9% male) with 631 treatment episodes (2280 anti-TNF-α treatment years) and 289 discontinuations of therapy. Female sex (adjusted hazard ratio [aHR] 1.42, 95% confidence interval [CI] 1.16-1.74), greater age at start of therapy per decade (aHR 1.15, 95% CI 1.04-1.27] and dose escalation (aHR 3.74, 95% CI 2.78-5.02) were associated with TNF-α inhibitor discontinuation. Total cohort cause-specific analysis identified female sex to be associated with side effects (aHR 4.05, 95% CI 2.36-6.98) but not to other discontinuation reasons. Adalimumab (aHR 1.70, 95% CI 1.11-2.60) and golimumab (aHR 4.97, 95% CI 2.30-10.74) use and dose-escalation (aHR 7.71, 95% CI 5.28-11.26) were associated with secondary loss of response. CONCLUSION: Drug persistence of anti-TNF-α therapy is lower in females as compared to males, mainly because of higher rates of side effects in females. Understanding the sex specific differences in effectiveness and safety of anti-TNF-α compounds can aid physicians in clinical decision-making

Risk of nonmelanoma skin cancer in patients with inflammatory bowel disease who use thiopurines is not increased.

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Pharmacological Activation of the Bile Acid Nuclear Farnesoid X Receptor Is Feasible in Patients with Quiescent Crohn's Colitis

<div><h3>Background</h3><p>The bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn's colitis (CC) exhibit reduced ileal FXR target gene expression. FXR agonists have been shown to ameliorate inflammation in murine colitis models. We here explore the feasibility of pharmacological FXR activation in CC.</p> <h3>Methods</h3><p>Nine patients with quiescent CC and 12 disease controls were treated with the FXR ligand chenodeoxycholic acid (CDCA; 15 mg/kg/day) for 8 days. Ileal FXR activation was assessed in the fasting state during 6 hrs after the first CDCA dose and on day 8, by quantification of serum levels of fibroblast growth factor (FGF) 19. Since FGF19 induces gallbladder (GB) refilling in murine models, we also determined concurrent GB volumes by ultrasound. On day 8 ileal and cecal biopsies were obtained and FXR target gene expression was determined.</p> <h3>Results</h3><p>At baseline, FGF19 levels were not different between CC and disease controls. After the first CDCA dose, there were progressive increases of FGF19 levels and GB volumes during the next 6 hours in CC patients and disease controls (FGF19: 576 resp. 537% of basal; GB volumes: 190 resp. 178% of basal) without differences between both groups, and a further increase at day 8. In comparison with a separate untreated control group, CDCA affected FXR target gene expression in both CC and disease controls, without differences between both groups.</p> <h3>Conclusions</h3><p>Pharmacological activation of FXR is feasible in patients with CC. These data provide a rationale to explore the anti-inflammatory properties of pharmacological activation of FXR in these patients.</p> <h3>Trial Registration</h3><p>TrialRegister.nl <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2009">NTR2009</a></p> </div

Disease characte.ristics of patients with Crohn's colitis at previous investigations and current investigation.

<p>Data presented as numbers (% of group).</p><p>Disease extent was divided in more or less than 50% colonic involvement; disease extent of more than 50% was defined as involvement of three or more anatomical parts of the colon;</p>*<p>disease behavior according to the Montreal Classification <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049706#pone.0049706-Satsangi1" target="_blank">[24]</a>.</p

Quality of life in patients with IBD during the COVID-19 pandemic in the Netherlands

Objective COVID-19 has put a strain on regular healthcare worldwide. For inflammatory bowel disease (IBD), gastrointestinal surgeries were postponed and changes in treatment and diagnostic procedures were made. As abrupt changes in treatment regimens may result in an increased morbidity and consequent well-being of patients with IBD, the aim of this study was to determine the effect of the COVID-19 pandemic on health-related quality of life (HRQoL) in patients with IBD. Design All patients with IBD who completed both Inflammatory Bowel Disease Questionnaire (IBDQ) and 36-Item Short Form Health Survey (SF-36) questionnaire between 31 August and 13 September 2020 were included in our cohort study. The primary end point was to determine the HRQoL in patients with IBD, measured by the IBDQ and SF-36 questionnaire. The secondary end point was determining which factors influence the HRQoL in patients with IBD. Results 582 patients with IBD filled in the IBDQ and SF-36 questionnaire. The HRQoL in our study population was low according to the questionnaires on both physical and mental subscales. In addition, multivariate analysis showed that increased age, female sex and patients who underwent surgery had a significantly lower HRQoL, most frequently on the physical domains in both questionnaires. Conclusion Patients with IBD had an overall low HRQoL during the COVID-19 pandemic. Furthermore, older patients, women and patients who underwent surgical procedures had the lowest physical HRQoL

Gallbladder dynamics in patients with Crohn's colitis and disease controls during the first 6 hours after CDCA ingestion and after 8 days of CDCA ingestion.

<p>Values are in means ± SD; CDCA, chenodeoxycholic acid; <i>V0</i>, baseline fasting gallbladder volume (mean of 3 measurements);<i>V_min</i> (mL), minimal gallbladder volume; <i>V_min</i> (%), minimal gallbladder volume as percentage of V0; <i>ΔV_min</i> (mL), difference between Vmin and V0; <i>ΔV_min</i> (%), percentual difference between Vmin and V0; <i>Time V_min</i> (hours), time to minimal gallbladder volume from t0; <i>V_max</i> (mL), maximal gallbladder volume; <i>V_max</i> (%), maximal gallbladder volume as percentage of V0; <i>ΔV_max</i> (mL), difference between Vmax and V0; <i>ΔV_max</i> (%), percentual difference between Vmax and V0; <i>Time V_max</i> (hours), time to maximal gallbladder volume from t0; <i>AUC</i> (mL*360 min), area under the curve of change of gallbladder volume during 360 minutes; <i>AUC</i> (percent*360 min), area under the curve of percentual change of gallbladder volume during 360 minutes; <i>V_t8</i> (mL), gallbladder volume after 8 days of CDCA ingestion; <i>V_t8</i> (%), <i>V_t8</i> as percentage of V0; <i>ΔV_t8</i> (mL), difference between V_t8 and V0; <i>ΔV_t8</i> (%), percentage difference between V_t8 and V0.</p

Plasma FGF19 levels (SEM) as a function of time after ingestion of chenodeoxycholic acid in patients with Crohn's colitis and disease controls.

<p>FGF19 levels progressively rise in all patients (p = 0.00) without differences between both groups Crohn's patients; Disease controls.</p