Anna Krajcovicova

Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases.

AIM To investigate the effect of vitamin D (VD) concentrations and VD supplementation on health related quality of life in inflammatory bowel disease (IBD) patients. METHODS A cohort of 220 IBD patients including 141 Crohns disease (CD) and 79 ulcerative colitis (UC) patients was followed-up at a tertiary IBD center. A subgroup of the cohort (n = 26) took VD supplements for > 3 mo. Health related quality of life was assessed using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ score were assessed between August and October 2012 (summer/autumn period) and between February and April 2013 (winter/spring period). The mean VD serum concentration and its correlation with disease activity of CD were determined for each season separately. In a subgroup of patients, the effects of VD supplementation on winter VD serum concentration, change in VD serum concentration from summer to winter, and winter sIBDQ score were analyzed. RESULTS During the summer/autumn and the winter/spring period, 28% and 42% of IBD patients were VD-deficient (< 20 ng/mL), respectively. In the winter/spring period, there was a significant correlation between sIBDQ score and VD serum concentration in UC patients (r = 0.35, P = 0.02), with a trend towards significance in CD patients (r = 0.17, P = 0.06). In the winter/spring period, VD-insufficient patients (< 30 ng/mL) had a significantly lower mean sIBDQ score than VD-sufficient patients; this was true of both UC (48.3 ± 2.3 vs 56.7 ± 3.4, P = 0.04) and CD (55.7 ± 1.25 vs 60.8 ± 2.14, P = 0.04) patients. In all analyzed scenarios (UC/CD, the summer/autumn period and the winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 50-59 ng/mL. Supplementation with a median of 800 IU/d VD day did not influence VD serum concentration or the sIBDQ score. CONCLUSION VD serum concentration correlated with health related quality of life in UC and CD patients during the winter/spring period.

Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients

OBJECTIVE There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it. DESIGN The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed. RESULTS The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL. CONCLUSIONS The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.

Delayed hypersensitivity reaction after initial dose of infliximab: a case report.

We report here an unusual case of delayed hypersensitivity reaction in a young woman with ulcerative colitis after the first administration of infliximab (IFX). The patient developed severe serum-sickness-like reaction, and her anti-IFX antibody titer increased rapidly after a single infusion of IFX. The possible reason for the delayed hypersensitivity reaction to a single IFX exposure might be the presensitization of the patient by murine antigens as she had been keeping mice and hamsters as pets for several years.

Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study

AIM To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients. METHODS During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury. RESULTS Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued. CONCLUSION Liver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

Therapeutic drug monitoring in the treatment of inflammatory bowel disease with infliximab

Abstract Tumor necrosis factors α (TNF) antagonists are currently widely used in patients with moderate to severe Crohns disease and ulcerative colitis. Approximately 50% of patients with inflammatory bowel disease (IBD) who initially benefit from treatment with TNF antagonists eventually lose response. However, the effect of the drug and its effectiveness is highly dependent on pharmacokinetics and pharmacodynamics. Therapeutic drug monitoring (TDM) is a new approach that measures drug levels and anti-drug antibodies (ADAb) to optimize treatment and achieve the best strategy in loss of response. Currently, there is no clear cut-off value that corresponds to the clinical response. ADAb production can cause a drop in levels or neutralize the drug, resulting in a loss of response. ADAbs may also contribute to infusion and injection reactions, thromboembolic events and serum sickness. This review article examines the evolution of TDM in the treatment of inflammatory bowel diseases. It examines the main contentions and developments surrounding the use of TDM in recent years, such as the level and loss of response, and describes current trends in TDM in clinical practice. Abstract TNF antagonists are currently commonly used in the treatment of moderate to severe forms of Crohns disease and ulcerative colitis. Approximately 50% of patients with non-specific inflammatory bowel disease (IBD), who initially benefited from treatment with TNF antagonists, will eventually lose their healing effect. The efficacy of treatment is highly dependent on pharmacokinetics and pharmacodynamics. Drug Therapeutic Drug Monitoring (TDM), which is Drug and Drug Antibody Measurement (ADAb), is a new approach to optimizing treatment and achieving the lowest risk of loss of response. At present, an exact therapeutic level that would match the clinical response is unclear. ADAb production may lead to decreased levels of drug neutralization resulting in a loss of therapeutic effect. Additionally, ADAb may contribute to infusion reactions, thromboembolic events and serum sickness. This article examines the development of TDM in the treatment of IBD. He examines the main TDM claims as well as the evolution of their use in recent years, examines the therapeutic range, the loss of response, and describes current trends in clinical practice.

Decrease of trabecular bone score reflects severity of Crohn’s disease: results of a case–control study

Objectives Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). Patients and methods The study was designed as a case–control study with the aim to assess and compare bone quantity and quality in patients with Crohn’s disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. Results The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm2 and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-&agr; therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. Conclusion For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.

Biologic treatment in comparison to methotrexate has positive effect on trabecular bone score in rheumatoid arthritis patients: 1-year follow-up

ABSTRACT Introduction: Biologic treatment may influence activity of rheumatoid arthritis (RA), as well as areal bone mineral density (aBMD). Decreased aBMD explains the fracture risk in RA patients only partially. The trabecular bone score (TBS), novel texture parameter reflects degradation of trabecular bone and therefore could be used as a further parameter to predict the risk of fragility fracture. Objective: To compare the effects of biological disease-modifying antirheumatic drugs (bDMARDs) and conventional synthetic (cs) DMARDs (methotrexate) on aBMD and TBS in patients suffering from active RA. Methods: A 12 month prospective trial was performed in 105 active RA patients. The cohort was divided into two groups: group 1 (n = 84, mean age 54 yrs) treated with bDMARDs and group 2 (n = 21, mean age 53 yrs) treated with csDMARDs. The mean daily dose of prednisone at baseline was 6.2 and 6.6 mg (NS) between group 1 and 2, respectively. Patients with anti-osteoporotic treatment were not included. All patients received calcium (600 mg) and cholecalciferol (800IU). Lumbar spine (LS) and FN aBMD (by DXA, Hologic) were measured at baseline and after 1 year of treatment. TBS was generated using TBS Insight software (Medimaps, Switzerland). Results: Treatment with bDMARDS led to decrease in mean prednisone dose and to increase of 1.7% (p < 0.05) in TBS and OC levels of 26% (p < 0.001) but not on aBMD and CTX after treatment. The greatest TBS increase (2.7%, p < 0.05) was observed in premenopausal females within group 1. No effect of csDMARDS on measured parameters was observed. Conclusion: Treatment of patients suffering from active RA with bDMARDs in comparison to csDMARDS led to increase of TBS, with greater increment of TBS in premenopausal women, despite no change in aBMD.

Trabecular bone score in patients with inflammatory bowel diseases

The cohort consisted of 84 IBD patients, 53 with Crohn’s disease (CD) and 31 with ulcerative colitis (UC). Clinical characteristics i.e. age, gender, anthropometry, clinical behaviour, medication were recorded. The BMD was determined by dual-energy X-ray absorptiometry (DXA, Hologic Discovery) at the lumbar spine. TBS was determined by TBS Insight® software (Medimaps, France). The clinical characteristics of the cohort are shown in table 1. TRABECULAR BONE SCORE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES

Sa1256 Combined Immunosuprpession, Corticoids and Menopause Have Significant Influcence on Bone Mineral Density in IBD Patients. A Prospective Study

a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG1-5 was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean MTXPGn concentration was observed between those with active disease and clinical remission. For each MTXPGn, a non-significant trend towards a higher measured concentration was observed in patients with active disease, (table 2). Conclusions: In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. References: [1]Dervieux T et al. Ann Rheum Dis,2005;64:1180-1185 [2]Stamp LK et al. Arth Rheum,2010;62:359-368 [3]Alenka JB et al,Ther Drug Mon,2007;29:619-625 Table 1. Patient Demographics