HLA-DQA1*05 Allele Carriage and Anti-TNF Therapy Persistence in Inflammatory Bowel Disease.

INTRODUCTION: Carriage of the HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADAs) to antitumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease. However, ADA is not uniformly associated with treatment failure. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of biologic therapy evaluated by drug persistence. METHODS: A multicenter, retrospective study of 877 patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy with HLA-DQA1*05 genotypes were generated by imputation from whole genome sequence using the HIBAG package, in R. Primary end point was anti-TNF therapy persistence, (time to therapy failure), segregated by HLA-DQA1*05 allele genotype and development of a risk score to predict anti-TNF therapy failure, incorporating HLA-DQA1*05 allele genotype status (LORisk score). RESULTS: In all, 877 patients receiving anti-TNF therapy were included in our study; 543 (62%) had no copy, 281 (32%) one copy, and 53 (6%) 2 copies of HLA-DQA1*05 allele. Mean time to anti-TNF therapy failure in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared with patients with 0 or 1 copy at 700 days' follow-up: 418 vs 541 vs 513 days, respectively (P = .012). Factors independently associated with time to anti-TNF therapy failure included carriage of HLA-DQA1*05 allele (hazard ratio [HR], 1.2, P = .02; female gender HR, 1.6, P < .001; UC phenotype HR, 1.4, P = .009; and anti-TNF therapy type [infliximab], HR, 1.5, P = .002). The LORisk score was significantly associated with shorter time to anti-TNF therapy failure (P < .001). CONCLUSIONS: Carriage of 2 HLA-DQA1*05 alleles is associated with less favorable outcomes for patients receiving anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in patients with IBD.

Our study found carriage of 2 copies of the HLA-DQA1*05 allele is associated with a less favorable response to anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in IBD patients.

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study.

BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register. RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51). CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.

BACKGROUND: The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. METHODS: Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). RESULTS: In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. DISCUSSION: In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided 'Constant-care' approach.

BACKGROUND: The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities' focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients' education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial 'Constant-care' was undertaken in Denmark and Ireland. METHODS: 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. RESULTS: 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group. CONCLUSION: The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.