Anna Fábián

Frequency and characteristics of infusion reactions during biosimilar infliximab treatment in inflammatory bowel diseases: results from Central European nationwide cohort

ABSTRACT Background: Safety data of the ‘real life’ use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres. Methods: Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically. Results: Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13 therapy was continued with the use of premedication. Cumulative ADA positivity rates were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure (30% vs. 3.1%, p < 0.001, OR 6.3 (2.7–14.6)) and ADA positivity (32.6% vs. 4.1%, p < 0.001, OR 19(5–73)) during the induction therapy were predictive factors for infusion reactions. Conclusions: Patients with previous exposure to anti-TNF-alpha and ADA positivity during the induction therapy were more likely to develop infusion reactions.

Infliximab biosimilar CT-P13 therapy is effective and safe in maintaining remission in Crohn’s disease and ulcerative colitis – experiences from a single center

ABSTRACT Background: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has been confirmed to be efficacious in inducing remission in inflammatory bowel diseases (IBD). The aim of this study was to evaluate the long-term efficacy and safety of CT-P13 therapy in Crohn’s disease (CD) and ulcerative colitis (UC), and to identify predictors of sustained clinical response during a 54-week CT-P13 treatment period. Patients and methods: Patients with CD and UC, who were administered CT-P13, were prospectively enrolled. Clinical response was assessed at week 14 and week 54. Predictive factors for disease outcome at week 54 were evaluated. Results: 57 CD and 57 UC patients were included; 55 CD and 49 UC patients completed the induction therapy and 50 CD and 46 UC patients completed the 54-week treatment period. Clinical remission was achieved in 65.5% of CD and 75.5% of UC patients at week 14. Rate of continuous clinical response was 51% in both CD and UC at week 54. None of the examined parameters were predictive to the clinical outcome neither in CD, nor in UC. Conclusion: This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD. Response rates at week 54 were similar in CD and UC.

Endoscopic retrograde pancreatography: When should we do it?

Endoscopic retrograde pancreatography (ERP) is an accurate imaging modality in the diagnosis of pancreatobiliary diseases. However, its use has been substantially reduced due to the invasiveness of procedure, the risk of complications and the widespread availability of non-invasive cross-section imaging techniques (computed tomography, magnetic resonance imaging, and endoscopic ultrasound). Since the introduction of endoscopic sphincterotomy, ERP has transformed from diagnostic method to an almost exclusively therapeutic procedure. Pancreatic duct injection substantially increased the risk of post-ERP pancreatitis (1.6%-15.7%); therefore, according to international guidelines ERP is recommended only in cases where biliary intervention is required. However, the role of ERP in the management of pancreatic diseases is currently not clearly defined, but in some cases the filling of pancreatic duct may provide essential information complementing the results of non-invasive imaging techniques. The aim of this publication is to systematically summarize the literature dealing with the diagnostic yield of ERP. We would like to define the precise indications of ERP and overview a diagnostic protocol of pancreatic diseases depending on international guidelines and the opinion of Hungarian experts, because it may improve the diagnostic accuracy, minimize of burden of patients and reduce the risk of procedure related complications.

Pregnancy does not affect fecal calprotectin concentration in healthy women

BACKGROUND/AIMS Noninvasive activity markers are extremely important in conditions, such as pregnancy, when endoscopy is not recommended. The aim of this prospective study was to determine fecal calprotectin (FC) concentrations in healthy non-pregnant and pregnant women and in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS Healthy pregnant and non-pregnant women and patients with active and inactive IBD were prospectively enrolled in this study. Demographic and clinical parameters and clinical disease activity scores in patients with IBD were recorded. Blood and stool samples of every patient were obtained to determine C-reactive protein and FC levels. FC levels were measured with a quantitative lateral flow assay. RESULTS One hundred and thirty-five subjects were enrolled in the study (24 non-pregnant and 48 pregnant healthy women, 40 non-pregnant patients with active IBD and 23 non-pregnant patients with inactive IBD). FC was significantly higher in active IBD patients than in pregnant (p<0.001) and non-pregnant healthy women (p<0.001). No difference could be detected in FC concentrations between pregnant and non-pregnant healthy women. CONCLUSION Since FC levels remained unchanged during pregnancy, it may be a useful noninvasive diagnostic tool in pregnancy for monitoring mucosal inflammation.

How disease extent can be included in the endoscopic activity index of ulcerative colitis: the panMayo score, a promising scoring system

BackgroundColonoscopy plays crucial role in the establishment of the diagnosis, management and follow-up of ulcerative colitis (UC). None of the currently widely used endoscopic scores consider disease extent, and therefore do not correlate with the real severity of UC. Our aim was to assess the accuracy of a new score, the Pancolonic Modified Mayo Score that can reflect not only the severity, but the extent of active UC.MethodsOne hundred and four UC patients were enrolled in this prospective study. The Endoscopic Mayo Scores of the involved area of the five colorectal segments were added; furthermore, the sum was multiplied by 3 in case of eMayo ≥2 (range 0 [normal] to 45 [most severe]) to obtain the Pancolonic Modified Mayo Score (panMayo) in order to clearly distinguish the active and inactive disease. We analysed the correlation of panMayo Score with eMayo and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and complicated disease outcome. We compared the endoscopic indices with serum and faecal inflammatory parameters and Riley Score.ResultsThe panMayo Score correlated with eMayo and UCEIS. Every endoscopic score showed correlation with Riley Score, CRP, haemoglobin, haematocrit, serum iron, faecal MMP-9 and calprotectin and also predicted a complicated disease outcome. Only panMayo score correlated exclusively with the extent of UC.ConclusionsWe suggest that this new score gives additional information about disease extent besides disease activity with a strong correlation with laboratory parameters of inflammation and with the other widely used endoscopic indices.

Clinical role, optimal timing and frequency of serum infliximab and anti-infliximab antibody level measurements in patients with inflammatory bowel disease

Background Serum infliximab (IFX) and antibody-to-infliximab (ATI) levels are objective parameters, that may have a great role in the therapeutic decisions during maintenance biological therapy. Research design and methods 48 inflammatory bowel disease patients receiving maintenance IFX therapy were prospectively enrolled and divided into adequate (complete remission N = 20) and inadequate responder (partial response, loss of response, dose escalation; N = 28) groups. Blood samples were collected just before (trough level, TL) and two (W2aTL) and six weeks (W6aTL) after the administration of IFX. Results Single measurement of ATI titer was insufficient for predicting therapeutic response due to transient expression of ATI, however, using the three points’ measurements, significant difference has been detected between the adequate and inadequate responder group (5.0% vs 35.7%; p = 0.016). The mean value of TL was significantly higher in the adequate responder group (3.11±1.64 vs.1.19±1.11; p<0.001) without further difference on the second and sixth week. Sensitivity and specificity for predicting the therapeutic response were 85.0% and 71.4% based on the cut-off value of TL 2.0 μg/ml. Conclusion Simultaneous measurement of serum IFX level prior to administration of regular IFX infusion and ATI titers significantly increase the diagnostic accuracy for the therapeutic decision in patients uncertainly responding to the therapy. The measurement of W2aTL and W6aTL levels did not result in further improvement in the prediction of therapeutic response.

Diagnostic Accuracy of Five Different Fecal Markers for the Detection of Precancerous and Cancerous Lesions of the Colorectum

Background. Colorectal cancer (CRC) is the second deadliest malignancy worldwide. This study aimed to compare the diagnostic accuracy of different fecal markers in the detection of colorectal adenomas and cancer. Methods. Stool samples of patients referred to colonoscopy were collected for the analysis of tumor M2 pyruvate kinase (M2PK), human hemoglobin (Hb), hemoglobin/haptoglobin (Hb/Hp) complex, fecal calprotectin (FC), and matrix metalloproteinase-9 (MMP-9). Results. Sensitivity and specificity of M2PK for adenomas sized > 1 cm were 60% and 67.5% and for CRC were 94.7% and 67.5%. Sensitivity and specificity of iFOBT for adenomas sized ≥ 1 cm were 80% and 72.5% and for CRC were 94.7% and 72.5%. Sensitivity and specificity of Hb/Hp complex for adenomas sized ≥ 1 cm were 80% and 52.9% and for CRC were 100% and 52.9%. Sensitivity of FC and MMP-9 for CRC was 77.8% and 72.2%. Combined use of M2PK, iFOBT, and FC resulted in a sensitivity and specificity of 95% and 47.5% for the detection of adenomas sized ≥ 1 cm. Discussion. In CRC, sensitivity of M2PK, iFOBT, and Hb/Hp complex proved to be high. Combined use of M2PK, iFOBT, and FC may be valuable in the detection of large adenomas.

The role of endoscopic ultrasonography in the diagnosis of rectal cancers

INTRODUCTION The exact extent of rectal cancer and regional lymph node involvement are essential for providing the optimal treatment. AIM The aim of the authors was to evaluate the diagnostic accuracy of endoscopic ultrasonography in routine clinical staging of rectal cancer. METHOD Outcomes of endoscopic ultrasonography performed between 2006 and 2012 for rectal cancer staging were retrospectively analyzed. The correlation between the endoscopic and pathological stages was evaluated. RESULTS In patients without neoadjuvant chemotherapy the sensitivity (75% and 73%) and specificity (74% and 80%) of endoscopic ultrasonography for differentiating T1 and T2 stages (respectively) were high, however, it was significantly decreased in differentiation of T3 stage (58%). A weak association was found in different N stages (45-62%). The diagnostic accuracy of endoscopic ultrasound was reduced significantly after the oncological treatment due to the overevaluation (27%) of the findings. After a relatively short learning curve (30 examinations) high correlation was detected between pT and uT stages. CONCLUSIONS Endoscopic ultrasonography provides great help in staging early rectal cancers. Due to the lower sensitivity in patients receiving neoadjuvant therapy, it is not a useful tool after down-staging.

Biological therapy and surgery rates in inflammatory bowel diseases – Data analysis of almost 1000 patients from a Hungarian tertiary IBD center

Inflammatory bowel diseases (IBD) [Crohn’s disease (CD) and ulcerative colitis (UC)], are chronic relapsing disorders of unknown etiology. The aim of this study was to determine demographic features, disease phenotypes, medical and surgical therapies in our IBD patients and to identify which parameters are in association with the need of surgery and/or biologic therapy. Data on demographic and clinical characteristics of the patients were analyzed from the IBD registry of the 1st Department of Medicine, University of Szeged. The study period was between January 2007 and March 2015. Data of 911 IBD patients (428 CD, 483 UC) were analyzed. The median lag time between onset of symptoms and diagnosis proved to be significantly longer in UC than in CD (4.6 years vs. 2.1 years, p = 0.01). 40% of the patients received biological therapy, 301 patients underwent surgery required more frequently for CD than UC. Surgery was more common in CD patients with ileal location and penetrating behaviour. In UC, more severe disease onset predicted to unfavourable disease course. Higher proportion of surgery was shown in patient aged above 40 years in both CD and UC. Diagnostic delay of more than 1 year and appendectomy predicted to unfavourable disease outcome of both CD and UC. This analysis revealed that more than 1 year of diagnostic delay, disease activity at diagnosis in UC, CD, ileal location and penetrating behaviour are factors that may influence disease outcome. Use of thiopurines seemed to be protective in UC.

The Use of Complementary and Alternative Medicine Is Less Frequent in Patients with Inflammatory Bowel Disease Than in Patients with Other Chronic Gastrointestinal Disorders

Background and Aims Complementary and alternative medicine (CAM) is commonly used among patients with inflammatory bowel diseases (IBD), but evidence about its real-life use is limited. We aimed to assess and compare CAM use in outpatients with IBD and other gastrointestinal diseases. Materials and Methods The use of herbs and botanicals, lifestyle modifications and mind/body therapies, patient satisfaction, and continuous use of conventional medicine were assessed with an anonymous questionnaire at a tertiary IBD unit in Hungary. 396 IBD patients (207 with Crohns disease, 185 with ulcerative colitis, and 4 with indeterminate colitis) and 164 patients with gastric acid-related diseases, premalignant and malignant colorectal diseases, lactose intolerance, celiac disease, dysbacteriosis, and so on were included. Results IBD patients reported significantly lower usage of herbs than did controls (25% versus 42%, p < 0.001). More than 90% of responding IBD patients continued conventional medication besides herbal remedies (83% in unaltered doses). IBD patients were more likely to implement lifestyle modifications (77% versus 63%, p = 0.0011), but not body/mind therapies (20% versus 15%, p = 0.1516). Younger age was a significant predictor of lifestyle modifications (p = 0.0246). Conclusions CAM use (especially that of herbal remedies) in IBD is less frequent than that in other gastrointestinal diseases. It is more a complementary than an alternative to conventional medicine in IBD. There is no significant difference between CAM use in patients with Crohns disease and that in patients with ulcerative colitis, although the latter tend to choose herbs; the benefit of which is supported by scientific evidence. This study is registered at the Medical Research Council, Hungary. This trial is registered with 3769/2010/1018EKU.