Background
Industrialization has been linked to the etiology of inflammatory bowel disease (IBD).
Aim
We investigated the association between air pollution exposure and IBD.
Methods
The European ...Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn’s disease (CD) (
n
= 38) and ulcerative colitis (UC) (
n
= 104) and controls (
n
= 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 μm (PM
10
), <2.5 μm (PM
2.5
), and between 2.5 and 10 μm (PM
coarse
), soot (PM
2.5 absorbance
), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs).
Results
Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM
2.5
and PM
10
, with ORs of 0.24 (95 % CI 0.07–0.81) per 5 μg/m
3
and 0.25 (95 % CI 0.08–0.78) per 10 μg/m
3
, respectively. There was an inverse but nonsignificant association for PM
coarse
. A higher nearby traffic load was positively associated with IBD OR 1.60 (95 % CI 1.04–2.46) per 4,000,000 motor vehicles × m per day. Other air pollutants were positively but not significantly associated with IBD.
Conclusion
Exposure to air pollution was not found to be consistently associated with IBD.
Summary
Background
Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 ...months of treatment.
Aim
The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands.
Methods
Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid‐free clinical remission (CSFR, Simple Clinical Colitis Activity Index SCCAI ≤2) at week 104. Secondary outcomes included biochemical remission (C‐reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate.
Results
We included 110 patients of whom 104 (94.5%) were anti‐TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty‐one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7–34). The main reasons for discontinuation were non‐response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib‐related adverse events per 100 patient‐years during follow‐up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient‐years.
Conclusion
Tofacitinib was effective in 31.8% of patients after 24 months of treatment.
Effectiveness and safety of tofacitinib for ulcerative colitis: Two‐year results of the ICC Registry
Summary
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.
GOAL AND BACKGROUND:A number of studies have investigated the effectiveness of cannabis or cannabinoids for treatment of inflammatory bowel diseases (IBD). We aimed to systematically analyze their ...effect in in the treatment of IBD patients.
STUDY:We included randomized controlled trials and nonrandomized studies analyzing IBD patients of any age using cannabi(noid)s. Two reviewers searched 3 databases until August 13, 2019. Primary outcome was clinical remission and secondary outcomes included inflammatory biomarkers, symptom improvement, quality of life (QoL) scores, and hospital outcomes. Risk of bias was assessed according to study type. The meta-analyses were performed using a random-effects model with subgroup analyses based on study type.
RESULTS:The search identified 682 records of which 15 nonrandomized studies and 5 randomized controlled trials were eligible for inclusion. The meta-analysis of the primary outcome included 146 randomized participants, all 18 years of age or older. Risk of bias was moderate. Cannabi(noid)s were not effective at inducing remission (risk ratio=1.56, 95% confidence interval=0.99-2.46). No effect on inflammatory biomarkers was observed. However, clinical symptoms (abdominal pain, general well-being, nausea, diarrhea, and poor appetite) all improved with cannabi(noid)s on Likert-scales. Baseline QoL scores were lower in patients using cannabis among cohort studies but improved significantly with cannabi(noid)s. Although length of hospital stay was shorter and risk of parenteral nutrition was lower in patients using cannabis, there was no effect on other IBD complications.
CONCLUSIONS:Cannabi(noid)s do not induce clinical remission or affect inflammation in IBD patients. However, cannabi(noid)s significantly improve patient-reported symptoms and QoL.
Previous studies have suggested a chemopreventive effect of 5-aminosalicylic acid (5-ASA) therapy in patients with inflammatory bowel disease (IBD). This effect has not been reported in IBD patients ...using thiopurines. We investigated the association between thiopurine or 5-ASA use and the risk of advanced neoplasia (AN), including high-grade dysplasia and colorectal cancer, in a large cohort of patients with IBD in the Netherlands.
PALGA, the nationwide network and registry of histo- and cytopathology in The Netherlands was linked to an anonymised computerised database of a Dutch health insurance company to identify patients with IBD with or without AN. Pharmaceutical data, including type and duration of medication use, were collected between January 2001 and December 2009. Cox proportional hazard regression analysis was used to calculate risk of AN in patients with and without thiopurine or 5-ASA use.
A total of 2578 patients with IBD were included. Of these, 973 patients (38%) used 5-ASA, 314 (12%) thiopurines, 456 (18%) both 5-ASA and thiopurines and 835 (32%) none of these drugs. Twenty-eight patients (1%) developed AN during 16,289 person-years of follow-up. Of these, 11 patients (39%) had used 5-ASA, two (7%) thiopurines and one (4%) both drugs. Thiopurine use was associated with a significantly decreased risk of developing AN (adjusted HR 0.10, 95% CI 0.01 to 0.75). 5-ASA therapy also had a protective effect on developing AN, but this was not statistically significant (adjusted HR 0.56, 95% CI 0.22 to 1.40).
Thiopurine use protects IBD patients against the development of AN. The effect of 5-ASA appeared to be less pronounced.
Specific nutrients or foods have been inconsistently associated with ulcerative colitis (UC) or Crohn's disease (CD) risks. Thus, we investigated associations between diet as a whole, as dietary ...patterns, and UC and CD risks.
Within the prospective EPIC (European Prospective Investigation into Cancer) study, we set up a nested matched case-control study among 366,351 participants with inflammatory bowel disease data, including 256 incident cases of UC and 117 of CD, and 4 matched controls per case. Dietary intake was recorded at baseline from validated food frequency questionnaires. Incidence rate ratios of developing UC and CD were calculated for quintiles of the Mediterranean diet score and a posteriori dietary patterns produced by factor analysis.
No dietary pattern was associated with either UC or CD risks. However, when excluding cases occurring within the first 2 years after dietary assessment, there was a positive association between a "high sugar and soft drinks" pattern and UC risk (incidence rate ratios for the fifth versus first quintile, 1.68 1.00-2.82; Ptrend = 0.02). When considering the foods most associated with the pattern, high consumers of sugar and soft drinks were at higher UC risk only if they had low vegetables intakes.
A diet imbalance with high consumption of sugar and soft drinks and low consumption of vegetables was associated with UC risk. Further studies are needed to investigate whether microbiota alterations or other mechanisms mediate this association.
Discontinuation of anti–tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be ...influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing.
This was a multicenter, prospective study in adult patients with Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3–4) versus complete (Mayo 0/SES-CD 0–2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use.
Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6–2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate aHR, 3.28; 95% confidence interval CI, 1.43–7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01–0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months.
The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.
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Abstract
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.
Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) ...and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD.
Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy.
A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased.
A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.
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.
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.
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.
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.
TrialRegister.nl NTR2009.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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