Ágnes Milassin

Efficacy of the new infliximab biosimilar CT-P13 induction therapy in Crohn’s disease and ulcerative colitis – experiences from a single center

Background: CT-P13 is the first biosimilar monoclonal antibody to infliximab (IFX); it has been approved for the same indications as its IFX counterpart in Hungary. The aim of this study was to assess the efficacy of CT-P13 induction therapy in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Patients diagnosed with CD and UC, who were administered CT-P13, were prospectively enrolled. Disease activity was estimated at the start and after the induction therapy. In patients with UC, sigmoideoscopy was also performed at the end of the induction therapy. Results: Eighteen CD and 21 UC patients were enrolled. Induction treatment was completed in 16 of the CD and 15 of the UC patients. In those with luminal CD, clinical response and remission was achieved in 6 (37.5%) and 8 (50%) of the patients at Week 8. In UC, clinical response and remission was achieved in 3 (20%) and 10 (66.7%) patients at Week 8. Mucosal healing was shown in 11 patients. Conclusions: This was the first study to prospectively evaluate the outcome of CT-P13 induction therapy in CD and UC. Our results confirm that induction with CT-P13 is safe and effective.

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.

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.

Prospective Comparison of Magnetic Resonance Imaging, Transrectal and Transperineal Sonography, and Surgical Findings in Complicated Perianal Crohn Disease

Magnetic resonance imaging (MRI) and transrectal sonography are the two accepted imaging modalities for evaluation of perianal fistulas and abscesses. Transperineal sonography is a new technique that is easy to learn and can be performed at any time. The purpose of this study was to prospectively compare the diagnostic accuracy of MRI, transrectal sonography, and transperineal sonography with surgical findings in patients with perianal Crohn disease.

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.

Is mucosal healing more common than clinical remission in ulcerative colitis? – Is it the truth or only a myth coming from the studies?

Abstract Background. The most important goals of the recent therapies of ulcerative colitis (UC) are to induce and maintain clinical remission and to achieve mucosal healing (MH). Rate of endoscopic remission has been shown to be higher than that of clinical remission in large trials like ULTRA and PURSUIT. The aim of our study was to evaluate the correlation between clinical and endoscopic disease activities of UC defined by activity scores. Methods. Clinical and endoscopic activities were evaluated in 100 consecutive UC patients. Clinical activities were defined by two activity indices: the Rachmilewitz Activity Index (CAI) and the partial Mayo score. Colonoscopies and patient enrollments were performed by two experienced gastroenterologists and endoscopists. They graded the findings both according to the endoscopic part of the Rachmilewitz Endoscopic Activity Index (EI) and the Mayo endoscopic subscore. MH was defined as Mayo endoscopic subscore and EI of 0. Histological activity was scored by Riley score. Results. Clinical and endoscopic activities showed strong correlations using both scoring systems (p = 0.0029 and p = 0.0001). Endoscopic disease activity also correlated with the histological activity (p ≥ 0.001). Significant correlation was shown between the clinical activity and MH (p = 0.0012 and p ≥ 0.001). No association was showed with the extension of the disease and clinical or endoscopic activity. Conclusion. Assessment of MH is very important for guiding therapy and for evaluation of remission in patients with UC. Our result showed good correlation between the clinical, endoscopic, and histological activities of UC focusing on the importance of evaluating the endoscopic activity of the patients.