Ágnes Anna Csontos

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 Crohns 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.

Efficacy and Safety of Adalimumab in Ulcerative Colitis Refractory to Conventional Therapy in Routine Clinical Practice.

BACKGROUND AND AIM Adalimumab [ADA] was approved for the treatment of ulcerative colitis [UC] refractory to conventional therapy in 2012 in Europe. Due to the observed discrepancies between clinical trials and practice, data on the outcome of ADA therapy are really needed from the real life. The aim of this study was to estimate the short- and long-term efficacy and safety of ADA in UC patients from each Hungarian biological centre. PATIENTS AND METHODS This prospective study consisted of UC patients treated with ADA in 10 Hungarian inflammatory bowel disease centres. The primary endpoints of the study were rates of continuous clinical response, remission, non-response and loss of response at Weeks 12, 30, and 52.The secondary endpoints included mucosal healing at Week 52 and the comparison of the efficacy of ADA between biological naive and infliximab [IFX]-treated groups. Colonoscopy was performed before starting the therapy and at Week 52. RESULTS In all, 73 active UC patients were enrolled in the study: 67.1% of the patients received previous IFX therapy; 75.3% of the patients showed short-term clinical response at Week 12. The probability of maintaining ADA was 48.6% at Week 52 with a continuous clinical response in 92% of these remaining patients. Mucosal healing was achieved in 48.1% of the patients at Week 52. Escalation of ADA was performed in 17.6%, and minor side effects developed in 4% of the patients; 5.4% of the patients underwent colectomy during the 1-year treatment period. CONCLUSION UC is a progressive disease that may need early aggressive therapy to prevent structural and functional complications. The results of our study demonstrated the favourable efficacy of short- and long-term ADA treatment for patients with UC.

Malnutrition risk questionnaire combined with body composition measurement in malnutrition screening in inflammatory bowel disease

The purpose of malnutrition screening is to predict the probability of a worse outcome due to nutritional factors. The Malnutrition Universal Screening Tool (MUST) can be used for screening in inflammatory bowel disease (IBD); however, it does not provide details about body composition. Our aim was to assess the body composition and combine this with the MUST method to screen risk of malnutrition and sarcopenia. A total of 173 IBD outpatients were enrolled in this cross-sectional study. The MUST scale indicated 21.4% of IBD patients to be at risk of malnutrition. A risk of sarcopenia was detected in 27.7%. However, one third of these patients were not considered to be at risk by their MUST score. Furthermore, Crohns disease (CD) patients had a strongly unfavorable fat-free mass index (FFMI) value compared to ulcerative colitis (UC) patients, and these differences were significant among men (FFMI: 18.62 ± 2.16 vs 19.85 ± 2.22, p = 0.02, in CD and UC males, respectively). As sarcopenia is a relevant prognostic factor, the MUST method should be expanded to include body composition analysis to detect more IBD patients at risk of malnutrition and sarcopenia in order to start their nutritional therapy immediately.

Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

INTRODUCTION AND OBJECTIVES coeliac disease (CD) and its cutaneous manifestation, dermatitis herpetiformis are both (DH) gluten-sensitive diseases. Metabolic bone disease is common among patients with CD, even in asymptomatic forms. Data are scarce about bone density in patients with dermatitis herpetiformis. The aim of our study was to compare bone mineral density (BMD) of celiac and dermatitis herpetiformis patients. METHODS 34 coeliac patients, 53 with dermatitis herpetiformis and 42 healthy controls were studied. The mean age was 38.0 +/- 12.1, 32.18 +/- 14.95, 35.33 +/- 10.41 years in CD, dermatitis herpetiformis, and healthy controls, respectively. Bone mineral density of the lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a body mass density (BMD) T-score between 0 and -1, between -1 and -2.5, and under -2.5, respectively. RESULTS at lumbar region, consisting of dominantly trabecular compartment, a decreased BMD was detected in 49 % (n = 26) patients with dermatitis herpetiformis, 62 % (n = 21) of CD patients, and 29 % (n = 12) of healthy controls, respectively. Lower BMD were measured at the lumbar region in dermatitis herpetiformis and CD compared to healthy subjects (0.993 +/- 0.136 g/cm2 and 0.880 +/- 0.155 g/cm2 vs. 1.056 +/- 0.126 g/cm2; p < 0.01). Density of bones consisting of dominantly cortical compartment (femoral neck) did not differ in dermatitis herpetiformis and healthy subjects. CONCLUSIONS our results show that a low bone mass is also frequent among patients with dermatitis herpetiformis. Bone mineral content in these patients is significantly lower in those parts of the skeleton which contain more trabecular than cortical bone.

Letter: body surface area and body muscle parameters may influence adalimumab trough levels.

SIRS, We read with great interest the publication by Lie et al. assessing the pharmacokinetic properties of adalimumab (ADA) and observing that body mass index (BMI) at the start of therapy may influence ADA levels at week 28. We have been interested in this topic also, so we would like to present our results and recommend them for further consideration. Some data show that BMI may influence the long-term efficacy of ADA in psoriasis, spondylo-arthritis and inflammatory bowel disease (IBD), but clear evidence to prove a relationship between ADA trough levels and efficacy is limited. Other data also support the fact that certain body parameters (e.g. body surface) may influence the clearance of monoclonal antibodies, particularly those that exhibit linear clearance, as ADA has. Our aim was to explore whether body composition influences ADA trough levels and its variability. We initiated ADA treatment (160/80/40EOW) in 18 IBD patients in our prospective study. ADA trough levels were measured at week 6 and 12. Body composition parameters, like fat-free mass index (FFMI), skeletal muscle index (SMI) and body fat mass index (BFMI) were measured by bioelectrical impedance analysis at inclusion. Similar to Lie et al., we found a stable intra-patient ADA level (8.00 2.9 lg/mL and 7.73 3.14 lg/mL at week 6 and 12, respectively). However, the intra-patient changes of ADA trough levels showed a negative correlation with body surface area (r = 0.682; P = 0.002) (Figure 1). Moreover, intra-patient ADA level variability correlated negatively with the parameters indicating muscle content of the patients (FFMI: r = 0.494, P = 0.045, SMI: r = 0.508, P = 0.038), but did not correlate with fat parameters (BFMI: r = 0.099, P = 0.708). These findings suggest that body surface area and body muscle parameters may influence the constancy of ADA trough levels. Results of our pilot study regarding the relationship between ADA trough levels and body composition need further confirmation in other studies.

Vitamin D level in Hungarian patients with inflammatory bowel diseases

INTRODUCTION Vitamin D has an important role in the immune regulation. Vitamin D is essential for innate and adaptive immune systems and it plays a significant role in the formation of immune tolerance, as well. AIM Vitamin D deficiency has been observed in patients with inflammatory bowel diseases in Western Europe, but there is no data available from Eastern Europe. METHOD The study included 169 patients with inflammatory bowel disease. RESULTS The median vitamin D level was 22.7±10.6 ng/ml. Only 20% of the patients had adequate vitamin D level (>30 ng/ml), 52% had vitamin D insufficiency (15-30 ng/ml), and 28% of them had severe vitamin D deficiency (<15 ng/ml). Vitamin D concentration failed to correlate with clinical activity indexes (partial Mayo score: r = -0.143; Crohns disease activity index: r = -0.253) and with inflammatory parameters (C-reactive protein: r = 0.008; erythrocyte sedimentation rate: r = 0.012). CONCLUSIONS Since vitamin D deficiency can be frequently observed in Hungarian patients with inflammatory bowel disease, its level should be tested in these patients.

P321 Vitamin D level doesn't correlate with disease extent and severity in Hungarian patients with inflammatory bowel disease

Background: Many patients with inflammatory bowel disease (IBD) face multiple problems, including medical, surgical, nutritional, social, psychiatric related to their disease and require a holistic approach to care. To address this need, a multidisciplinary, prompt access IBD clinic was established at McMaster University Medical Centre, Hamilton, Canada. The prevalence of anxiety and depression among the patients attending the clinic is not known. Methods: Interdisciplinary team members consisting of gastroenterologists, surgeon, psychiatrists, nurse practitioner and dietitian providing prompt access holistic care for patients with IBD. All patients with IBD were assessed for demographic characteristics, quality of life using the Short Form-12 (SF-12), and psychological morbidity using the Hospital Anxiety and Depression Scale (HADS). The SF-12 has two components; physical composite score (PCS) and mental composite score (MCS); if either score is ,50 it was considered abnormal. HADS score can range from 0-42 and a score of .11 was considered abnormal. Results: The mean (SD) age of the 67 patients (males, 36%) was 35 (13) yrs. The majority (63%) had received college education. Of them, 40% had full-time employment, 18% had parttime employment, 24% were unemployed and 18% were on disability/sick leave. Of the 67 patients, 45% were in a stable marital relationship, 43% were single and 10% were either divorced or separated. The mean (SD) PCS was 41 (11) and MCS was 43 (12). The PCS was abnormal in 73% and MCS in 65% of the patients. HADS scores indicated that 75% were anxious/ depressed, while 8% had borderline anxiety/depression and 17% had normal scores. HADS scores showed a high degree of correlation with MCS (r=-0.717; p ,0.001) but no relationship to PCS, ESR or CRP. HADS scores were lower in those with higher income (.60,000

A táplálásterápia hatékonyságának vizsgálata gyulladásos bélbetegségben szenvedők gondozása során

/yr) than those with lower income (15±8 vs 21±6; p=0.037); and in those who had full time employment compared to those without (13±7.6 vs 17±8; p=0.05). The PCS showed a negative correlation with ESR (rho=-0.25; p=0.048) and CRP (rho=-0.25; p= 0.05). Only 27% (13/49) of the patients with abnormal HADS score received professional psychiatric help. Conclusions: Patients with IBD have a high prevalence of anxiety and depression. Anxiety and depression was found more often in those with lower income and no full time employment.. HADS score did not show any relationship to disease activity or physical functional capability. Patients with IBD need active evaluation for presence of underlying anxiety or depression.

Body composition assessment of Crohn’s outpatients and comparison with gender- and age-specific multiple matched control pairs

Absztrakt: Bevezetes: A gyulladasos belbetegsegben szenvedő betegeknel koros taplaltsagi allapot alakulhat ki (gyulladasos citokinek termelődese, műtetek utani katabolizmus, beszűkult etrend miatt), amit taplalasterapia elrendelese mellett is nehez hatekonyan kezelni. Celkitűzes: A taplalasterapia hatekonysaganak vizsgalata. Modszer: Kombinalt taplaltsagi allapot rizikoszűrese (kerdőives felmeressel es bioimpedancias testosszetetel-analizissel) a vizsgalat elejen es az egyeves vizsgalati periodus vegen. Eredmenyek: A 205 betegből 82 bizonyult veszelyeztetettnek. Osszesen 44-en reszesultek hosszu tavu taplalasterapiaban, 45%-uknak elegendő volt a dietamodositas, 50% oralis es 5% parenteralis taplalast is igenyelt. A mindket meresi eljaras alapjan magas rizikojunak minősulők szama a beavatkozasokkal 31-ről 21 főre csokkent, a teljes es a zsirmentes testtomeg nyolc, illetve kilenc esetben 10%-ot meghaladoan novekedett, a tomegindexek (∆BMI: +1,3 kg/m2, p = 0,035, s.; ∆FFMI: +0,5 kg/m2, p = 0,296, n. s.) szin...INTRODUCTION Inflammatory bowel diseases can cause malnutrition (due to inflammatory cytokine production, catabolic states after surgery, restricted diet), which is difficult to treat by nutritional therapy. AIM Investigating the efficacy of nutrition therapy. METHOD Combined malnutrition risk screening (questionnaires and body composition analysis), at the beginning of the research and after a 1 year period. RESULTS 205 patients were screened, 82 were malnourished. A total of 44 received nutritional intervention for 1 year, for 45% dietary management was satisfactory, 50% needed oral nutritional supplements and 5% received home parenteral nutrition. These interventions reduced the number of patients considered by both measuring methods in high risk from 31 to 21, increased the body weight and fat-free mass in 8 and 9 cases significantly (i.e., with more than 10%), and improved the indices as well (ΔBMI: +1.3 kg/m2, p = 0.035 s., ΔFFMI: +0.5 kg/m2, p = 0.296 n.s.). The main limitations of our research are the relatively low number of cases and the mono-centric involvement. CONCLUSIONS We recommend combined malnutrition risk screening for all patients with inflammatory bowel disease due to the high risk of malnutrition, and follow-up of the malnourished patients to monitor the efficacy of their nutrition therapy. Orv Hetil. 2017; 158(19): 731-739.

Az adalimumab hatékonysága és biztonságossága hagyományos kezelésre refrakter colitis ulcerosában

Background/Objectives:Routine clinical care for Crohn’s disease (CD) outpatients does not cover the assessment of body composition (BC); although this disease (because of inflammation, surgeries, lack of physical activity and appetite) may have a severe impact on lean body mass. The main aims of this prospective research were to assess the nutritional status of the patients and to compare their data with apparently healthy gender- and age-specific matched control pairs.Subjects/Methods:Overall, 136 CD patients and 1752 apparently healthy people were involved in the study. All participants were measured by the same bioelectrical impedance analyser.Results:Using body mass index (BMI) and fat-free mass index (FFMI) as the markers of nutritional status, we found low BMI for 21% of the patients and low FFMI for 30% of them. Low BMI values were not gender specific, but substantially more females had low FFMI values. Low BMI was diagnosed in the patients’ vs the control group for 21 vs 4% for men and 21 vs 2% for women; whereas low FFMI was diagnosed for 25 vs 5% for men and 36 vs 14% for women. Significant differences were found between patients’ and control groups (median BMI: 22.0 vs 25.1 kg/m2, P<0.0001; FFMI: 17.3 vs 18.4 kg/m2, P=0.0044).Conclusions:This study confirmed the higher prevalence of low FFMI than that of low BMI among the subjects. We recommend implementing the assessment of BC into routine clinical care to diagnose low FFMI and to start intervention in time.