Utility of serological markers in inflammatory bowel diseases: Gadget or magic?

The panel of serologic markers for inflammatory bowel diseases (IBD) is rapidly expanding. Although anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn’s disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS: About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS: Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course

Trading between perceived risks and benefits related to biosimilar biological treatment in Crohn’s disease; discrete choice experiment among gastroenterologists

Objective: The objective of the study is to explore preferences of gastroenterologists for biosimilar drugs in Crohn’s Disease and reveal trade-offs between the perceived risks and benefits related to biosimilar drugs. Method: Discrete choice experiment was carried out involving 51 Hungarian gastroenterologists in May, 2014. The following attributes were used to describe hypothetical choice sets: 1) type of the treatment (biosimilar/originator) 2) severity of disease 3) availability of continuous medicine supply 4) frequency of the efficacy check-ups. Multinomial logit model was used to differentiate between three attitude types: 1) always opting for the originator 2) willing to consider biosimilar for biological-naïve patients only 3) willing to consider biosimilar treatment for both types of patients. Conditional logit model was used to estimate the probabilities of choosing a given profile. Results: Men, senior consultants, working in IBD center and treating more patients are more likely to willing to consider biosimilar for biological-naïve patients only. Treatment type (originator/biosimilar) was the most important determinant of choice for patients already treated with biologicals, and the availability of continuous medicine supply in the case biological-naïve patients. The probabilities of choosing the biosimilar with all the benefits offered over the originator under current reimbursement conditions are 89% vs 11% for new patients, and 44% vs 56% for patients already treated with biological. Conclusions: Gastroenterologists were willing to trade between perceived risks and benefits of biosimilars. The continuous medical supply would be one of the major benefits of biosimilars. However, benefits offered in the scenarios do not compensate for the change from the originator to the biosimilar treatment of patients already treated with biologicals

Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations

Background: Haptoglobin (Hp) α-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. Methods: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes. Results: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20–1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60–3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. Conclusions: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule’s structural and functional properties

Subjective expectations regarding longevity and future health:a cross-sectional survey among patients with Crohn’s disease

AimThe aim was to explore the subjective healthexpectations (sHE) of patients with Crohn’s disease(CD) for both the near future and the elderly.MethodA cross-sectional survey was performed in fourgastroenterology centres in Hungary. Consecutive outpa-tients with CD with age≥18 were recruited. Socio-demo-graphic and disease characteristics were recorded and theCrohn’s Disease Activity Index (CDAI), Perianal DiseaseActivity Index, Patients’ Global Assessment (PGA) andcurrent pain visual analogue scale (VAS) were assessed.Subjective life expectancy (sLE) was explored and com-pared to statistical life expectancy. Current health and sHEfor 1 year ahead and for ages 60/70/80/90 were assessedusing the descriptive system of the EQ-5D-3L.ResultsIn all, 206 patients (54.9% men) with a meanage of 34.7 (SD 10.5 years) and disease duration of10.5 (SD 6.3) years were studied. The CDAI score was110.5 (SD 77.0) and 66% were treated by biologicdrugs. Mean current EQ-5D-3L score was 0.80 (SD0.17) and patients expected a 0.05 (SD 0.15) improve-ment within a year (P<0.05). For ages 60/70/80/90,a mean EQ-5D-3L score of 0.59, 0.38, 0.10 and 0.12 respectively was provisioned. Age, current healthstatus, sLE, PGA and pain VAS showed significant cor-relation with both 1-year and older age sHE(P<0.05). Long-term sHE and sLE were negativelyaffected by the presence of extraintestinal manifestationsbut not by previous CD-related surgery.ConclusionPatients with CD expect severe deteriora-tion in health in later life. Given that unrealistic sHEmay affect patients’ current quality of life and healthbehaviour, we encourage physicians to explore and con-sider CD patients’ sHE in clinical care

Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: a prospective, multicentre, nationwide cohort

Background and Aims: Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. Methods: A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn’s disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. Results: In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [ p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. Conclusions: This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions