T3-T4 index as a prognostic marker of response to biological treatments in elderly patients with inflammatory bowel disease.

Following the growing trend of trying to individualise treatment in inflammatory bowel disease and in view of the challenge posed by elderly patients requiring biologic treatments, we have conducted a study in our centre to assess the T3/T4 index as a predictor of response to biologic treatments in elderly patients.

Effectiveness and safety of ustekinumab dose escalation in Crohn's disease: a multicenter observational study.

BACKGROUND: ustekinumab has proven effective in Crohn's disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. AIM: to evaluate the effectiveness of ustekinumab dose escalation in CD. METHODS: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. RESULTS: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. CONCLUSION: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.

Vitamin D and inflammatory bowel disease: what do we know so far?

In the last years,several studies have focused on the involement of vitamin D in different physiological and pathological processes. One of the most interesting actions occurs in the Inflammatory bowel disease, where a higher prevalence of vitamin D deficiency has been observed. This study aimed to review the literature in order to explain its relationship with the disease, the risk factors, measuring the importance of sun exposure, describing how treatments are affected or observing the effect of vitamin supplementation in this type of patients.

Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence and association with clinical-biological activity.

INTRODUCTION: there are few data on the prevalence of vitamin D deficiency in patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be associated with a worse course of the disease. AIM: to determine the prevalence of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and assess its association with clinical and biological activity, quality of life and psychological symptoms. METHODS: a cross-sectional, single-center observational study was performed. The study variables were obtained via clinical interviews, medical chart review and validated questionnaires (Hospital Anxiety and Depression Scale and Short Quality of Life in Inflammatory Bowel Disease Questionnaire). 25OHD was measured in the same laboratory by an electro-chemiluminescence immunoassay. RESULTS: the study included 224 patients. The prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was 33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was associated with a higher clinical activity (p < 0.001) and a higher concentration of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with clinical activity (p < 0.001), the use of steroids during the last six months (p = 0.001) and hospital admission during the previous year (p = 0.003). A sub-analysis of 149 patients failed to detect an association between vitamin D and quality of life or the scores of the Hospital Anxiety and Depression Scale. CONCLUSIONS: vitamin D deficiency is common in patients with inflammatory bowel disease. An association was found between vitamin D concentration and clinical activity indexes, as well as fecal calprotectin levels in Crohn's disease.

Sunlight exposure in inflammatory bowel disease outpatients: Predictive factors and correlation with serum vitaminD. / Exposición solar en la enfermedad inflamatoria intestinal ambulatoria: factores predictivos y correlación con la concentración sérica de vitamina D.

INTRODUCTION: Sunlight exposure is the main source of vitaminD. Our aim was to describe both sun exposure and sun protection behaviour in a series of patients with inflammatory bowel disease (IBD), and to study their potential association with vitaminD concentration. PATIENTS AND METHODS: A cross sectional, observational study. The clinical-demographic variables were obtained via clinical interviews and medical history review. The sunlight exposure assessment was carried out using the Sun Exposure Questionnaire and the concentration of 25-hydroxy vitaminD (25OHD) was measured by an electro-chemiluminescence immunoassay. Questionnaires were conducted on quality of life, physical activity, weekly vitaminD intake and sun protection behaviour. RESULTS: 149 patients were included. In 69% of patients, deficient or insufficient 25OHD values were recorded. 67% showed low sun exposure. A modest significant correlation was observed between the total score of the solar exposure questionnaire and the 25OHD concentration in the complete series (r=0.226, P=.006) and in the summer (r=0.274, P=.01). The sun protection behaviour questionnaire score did not influence the 25OHD concentration. In the multivariate analysis, only the presence of clinical activity was associated with low sun exposure (OR=3.23). DISCUSSION: Sun exposure according to the questionnaire used was low, was associated with the presence of clinical activity and was weakly correlated with serum 25OHD concentration. More studies are needed to explore the use of individual questionnaires for sun exposure and its relationship with vitaminD in patients with IBD.

Medium to long-term efficacy and safety of oral tacrolimus in moderate to severe steroid refractory ulcerative colitis.

BACKGROUND AND OBJECTIVE: Oral tacrolimus is an effective drug that induces clinical remission in patients with moderate to severe ulcerative colitis refractory to steroids. However, there is little data with regard to its medium to long-term efficacy and safety. The aim of this study was to assess the medium to long-term efficacy and safety of oral tacrolimus in this challenging clinical situation. METHODS: This was a retrospective observational review of the clinical charts of 34 patients with moderate to severe ulcerative colitis refractory to steroids treated with oral tacrolimus at our hospital (July 2001-July 2016). Remission was defined as a Lichtiger index score < 3 and response was defined as a score < 10 with a reduction of at least three points compared to the baseline score. RESULTS AND CONCLUSIONS: Seven patients (20.58%) required colectomy during the follow-up period (mean 65 months). Nine patients required rescue with infliximab (four patients during the first six months of follow-up and the other five after the first six months). The short to medium clinical efficacy combining both remission and clinical response was 82% at six months. Kaplan-Meier analysis showed that the percentage of patients free from colectomy and additional sequential rescue therapy was 75% at 54 months (median follow-up). The early introduction of thiopurines (< 2 months from start of tacrolimus) showed no significant improvement in prognosis (p = 0.72). Fifty-three per cent of patients experienced adverse effects, none of whom required treatment withdrawal. No severe infections were noted during the follow-up.

Efficacy and safety of vedolizumab as a treatment option for moderate to severe refractory ulcerative colitis in two patients after liver transplant due to primary sclerosing cholangitis.

Vedolizumab is a humanized IgG1 monoclonal antibody that selectively blocks the lymphocyte integrin α4ß7 and prevents its interaction with endothelial adhesion molecules and subsequent transmigration to the gastrointestinal tract. The drug was approved in 2014 for the induction and maintenance treatment of ulcerative colitis and moderate to severe Crohn's disease that is refractory or intolerant to conventional treatment with corticoids and immunosuppressants and/or anti-TNFα drugs. However, inflammatory bowel disease has a variable behavior following liver transplant. One third of patients with ulcerative colitis associated with primary sclerosing cholangitis are expected to deteriorate despite receiving immunosuppression to prevent rejection. There is limited experience with anti-TNFα agents in patients with inflammatory bowel disease in the setting of liver transplantation and the studies to date involve a limited number of cases. The efficacy and safety data of vedolizumab in this situation are unreliable and very preliminary. We present two cases with the aim to present the efficacy and safety of vedolizumab after one year of treatment in two patients who underwent a transplant due to primary sclerosing cholangitis. One case had de novo post-transplant ulcerative colitis refractory to two anti-TNFα drugs (golimumab and infliximab). The other patient had a colostomy due to fulminant colitis and developed severe ulcerative proctitis refractory to infliximab after reconstruction with an ileorectal anastomosis.

Vitamin D in Inflammatory Bowel Disease: Biological, Clinical and Therapeutic Aspects.

BACKGROUND: Vitamin D has an immunoregulatory action in Inflammatory Bowel Disease (IBD) as well as other immune-mediated disorders. Its influence on intestinal permeability, innate and adaptive immunity, and the composition and diversity of the microbiota contribute to the maintenance of intestinal homeostasis. Patients with IBD have a greater prevalence of vitamin D deficiency than the general population, and a possible association between this deficit and a worse course of the disease. However, intervention studies in patients with IBD have proved inconclusive. OBJECTIVE: To review all the evidence concerning the role of vitamin D as an important factor in the pathophysiology of IBD, review the associations found between its deficiency and the prognosis of the disease, and draw conclusions for the practical application from the main intervention studies undertaken. METHODS: Structured search and review of basic, epidemiological, clinical and intervention studies evaluating the influence of vitamin D in IBD, following the basic principles of scientific data. RESULTS: Vitamin D deficiency is associated with disease activity, quality of life, the consumption of social and healthcare resources, and the durability of anti-TNFα biological treatment. Determination of new metabolites of vitamin D, measurement of its absorption capacity and questionnaires about sun exposure could help identify groups of IBD patients with a special risk of vitamin D deficiency. CONCLUSION: Well-designed intervention studies are needed in IBD, with probably higher objective plasma doses of vitamin D to establish its efficacy as a therapeutic agent with immunomodulatory properties. Meanwhile, vitamin D deficiency should be screened for and corrected in affected patients in order to achieve adequate bone and phosphocalcic metabolism.