Maastricht University Medical Centre and Ferring.

No abstract

Background and Aims Ustekinumab is approved for the treatment of Crohn’s disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. Methods We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. Results In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3–58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response. Conclusion Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.

TLR2 and its cofactors TLR1 and TLR6 are involved in the initial immune response to bacteria by recognizing peptidoglycan. An association between nonsynonymous variants in the TLR1, -2, and -6 genes and extensive colonic disease in UC and CD was found. Our findings further highlight the role of an abnormal innate immune response in the pathogenesis of IBD.

Summary Background:  Major depressive disorder is the most common psychiatric diagnosis in Crohn's disease. In other chronic diseases, evidence suggests that depression influences the course of the disease. Strong evidence of such a mediating role of major depressive disorder in Crohn's disease has never been found.Aim:  To assess the relationship between major depressive disorder and outcome of treatment of luminal Crohn's disease with infliximab.Methods:  In this prospective study, 100 consecutive unselected patients underwent assessment of psychosocial, demographical disease‐related biological and clinical parameters at baseline and at 4 weeks after infliximab. Major depressive disorder was diagnosed using the Patient Health Questionnaire. Subsequently, the patients were followed up clinically until the next flare or during 9 months.Results:  The Crohn's disease responded in 75% of the patients, and remission was achieved in 60%. The presence of major depressive disorder at baseline predicted a lower remission rate (OR = 0.166, 95% CI = 0.049–0.567, P = 0.004). At follow‐up, 88% of the patients needed retreatment. At univariate regression analysis, major depressive disorder significantly decreased time to retreatment (P = 0.001). Multivariate Cox regression confirmed major depressive disorder as an independent determinant of active disease both at baseline and at re‐evaluation (hazard ratio = 2.271, 95% CI: 1.36–3.79, P = 0.002).Conclusion:  Major depressive disorder is a risk factor for failure to achieve remission with infliximab and for earlier retreatment in patients with active luminal Crohn's disease. Assessment and management of major depressive disorder should be part of the clinical approach to patients with Crohn's disease.