Inflammatory bowel disease (IBD) is a complex multifactorial disorder in which external and environmental factors have a large influence on its onset and development, especially in genetically susceptible individuals. Crohn’s disease (CD), one of the two types of IBD, is characterized by transmural inflammation, which is most frequently located in the region of the terminal ileum. Oxidative stress, caused by an overabundance of reactive oxygen species, is present locally and systemically in patients with CD and appears to be associated with the well-described imbalanced immune response and dysbiosis in the disease. Oxidative stress could also underlie some of the environmental risk factors proposed for CD. Although the exact etiopathology of CD remains unknown, the key role of oxidative stress in the pathogenesis of CD is extensively recognized. Epigenetics can provide a link between environmental factors and genetics, and numerous epigenetic changes associated with certain environmental risk factors, microbiota, and inflammation are reported in CD. Further attention needs to be focused on whether these epigenetic changes also have a primary role in the pathogenesis of CD, along with oxidative stress.

Summary: Background: Effectiveness of vedolizumab in real world clinical practice is unknown.Aim: To evaluate the short and long‐term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD).Methods: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey‐Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short‐term response was assessed at week 14. Variables associated with short‐term remission were identified by logistic regression analysis. The Kaplan‐Meier method was used to evaluate the long‐term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response.Results: 521 patients were included (median follow‐up 10 months [interquartile range 5‐18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient‐year of follow‐up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent.Conclusions: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short‐ and long‐term response. Vedolizumab seems to be safe in clinical practice.

Treatment with antitumor necrosis factor-alpha (anti-TNF-α) offers a significant improvement in several immune-based diseases, including Crohn's disease (CD) and psoriasis. Different cutaneous side effects have been described for anti-TNF-α therapy such as psoriasis. Previous reports showed that inhibition of TNF-α can induce over expression of cutaneous IFN-α, which in turn caused a predisposition to psoriasis. We report a 31-year-old woman with extensive CD and perianal lesions, without response to conventional treatment. She paradoxically developed a cutaneous eruption with psoriasiform morphology and distribution during treatment with both anti-TNF-α approved in Europe for CD, infliximab and adalimumab. These lesions cleared after topical application of corticosteroids and cessation of the anti-TNF-α treatment. Due to uneffectiveness of pharmacological treatment on disease, the patient had to undergo surgery. TNF-induced psoriasis in patients with CD is rare and has been previously documented with infliximab or adalimumab. The reason for this apparently paradoxical effect of the therapy is still unclear. This is the first case of psoriasis induced first by infliximab and later by adalimumab in the same CD patient. We would like to review and to draw attention about psoriasis as a cutaneous side effect with anti-TNF-α treatments.

Summary: Background: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies.Aim: To assess the real‐world, short‐term effectiveness of ustekinumab in refractory Crohn's disease (CD)Methods: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey‐Bradshaw Index (HBI), C‐reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined.Results: Three hundred and five patients were analysed (≥2 previous anti‐TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti‐TNF agent and fewer previous anti‐TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response.Conclusion: This is the first study to show the real‐world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Summary: Background: Data on the long‐term administration of ustekinumab in recommended doses are limited.Aim: To assess the real‐world, long‐term effectiveness of ustekinumab in refractory Crohn's disease (CD).Methods: Multi‐centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey‐Bradshaw Index (HBI), endoscopic activity, C‐reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined.Results: A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti‐TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission.Conclusion: After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.

Vitamin D has recently been discovered to be a potential immune modulator. Low serum vitamin D levels have been associated with risk of relapse and exacerbation of clinical outcomes in Crohn’s disease (CD) and ulcerative colitis (UC). A retrospective, longitudinal study was conducted to determine the association between vitamin D levels and inflammatory markers and clinical disease activity in inflammatory bowel disease (IBD). In addition, circulating 25(OH)D₃ progression was evaluated according to vitamin D supplementation. Participants were separated into three groups according to their vitamin D level: severe deficiency (SD), moderate deficiency (MD) and sufficiency (S). Serum 25(OH)D₃ was inversely correlated with faecal calprotectin (FC) for CD and UC but was only correlated with C-reactive protein (CRP) for UC patients. In the multivariate analysis of FC, CRP and fibrinogen (FBG), we predicted the presence of a patient in the SD group with 80% accuracy. A deficiency of 25(OH)D₃ was associated with increased hospitalisations, flare-ups, the use of steroids and escalating treatment. Supplemental doses of vitamin D were likely to be insufficient to reach adequate serum levels of 25(OH)D₃. Vitamin D intervention studies are warranted to determine whether giving higher doses of vitamin D in IBD might reduce intestinal inflammation or disease activity.