Anita Bálint

Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy

Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy.

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.

The Diagnostic Value of a New Fecal Marker, Matrix Metalloprotease-9, in Different Types of Inflammatory Bowel Diseases

BACKGROUND Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohns disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD. METHODS Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay. RESULTS Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis. CONCLUSIONS This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation.

Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease

AIM To assess tumor necrosis factor-α (TNF-α), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-α therapy. METHODS Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group I) and 31 patients in complete clinical remission (Group II) selected as a control group were collected to measure trough serum TNF-α level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-α, IFX trough levels, and ATI concentrations. RESULTS The serum TNF-α level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them. CONCLUSION On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

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.

Long-term outcome of cyclosporin rescue therapy in acute, steroid-refractory severe ulcerative colitis.

Background Although cyclosporin is effective in severe ulcerative colitis (UC), long-term colectomy rate varies between 60 and 88% among patients in whom cyclosporin initially induced remission. The aim of our study was to evaluate the long-term outcome and the optimal duration of cyclosporin therapy in acute, severe UC. Methods A total of 73 patients underwent i.v. cyclosporin therapy for a steroid refractory flare up of UC between 1998 and 2009. All patients were treated with 1 mg/kg i.v. methylprednisolone for 3–7 days before the administration of cyclosporin. Patients received i.v. cyclosporin of 4–5 mg/kg for 5 days following oral treatment. Results The mean follow up after the initiation of cyclosporin was 4.2 years. There were 20 patients who underwent early colectomy. Cyclosporin had to be discontinued due to side effects in 22 patients. Cyclosporin failed and late colectomy was performed in 14 of the 53 responders. Duration of cyclosporin treatment was significantly longer in those who avoided colectomy. The probability of avoiding colectomy proved to be 66% in case of 1-year treatment period with cyclosporin. The longer treatment period resulted in longer colectomy-free disease course. Conclusions Cyclosporin is effective in acute, severe UC during long-term follow up. Our data suggest that the longer cyclosporin is used, the more it is possible to avoid colectomy in the future.

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.

Long-term increase in serum cholesterol levels in ulcerative colitis patients treated with cyclosporine: an underdiagnosed side effect frequently associated with other drug-related complications.

Abstract Introduction. Several serious side effects may limit the use of cyclosporine. Cyclosporine has been reported to increase the total cholesterol level; however, the change in serum cholesterol levels before and after cyclosporine therapy has not been examined in ulcerative colitis (UC) patients. The purpose of this article was to compare serum cholesterol levels before and after cyclosporine therapy in patients with refractory UC and to examine the relationship between serum cholesterol levels and other common side effects. Patients and methods. We prospectively assessed serum cholesterol levels in UC patients who had been treated with cyclosporine. Data of 72 patients were analyzed and compared to a control group treated with Infliximab. Results. The average duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. Elevated cholesterol levels were detected in 47.2% of the patients. Serum cholesterol levels were significantly increased during and after discontinuation of cyclosporine therapy compared to the time before use of the drug. However, cholesterol levels measured during cyclosporine therapy were significantly higher compared to the time after its discontinuation (p < 0.001). Patients with drug-related side effects showed higher cholesterol levels after discontinuation of the therapy compared to those who did not experience any adverse events. Conclusions. Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in the long-term, after discontinuation of the therapy. Considering that significantly higher post-therapy cholesterol levels were more common in patients who developed drug-related complications, routine measurement of serum cholesterol may increase the safety of the drug.

Tuberculin skin test and quantiferon in BCG vaccinated, immunosuppressed patients with moderate-to-severe inflammatory bowel disease

BACKGROUND AND AIMS There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. METHODS 166 consecutive moderate-to-severe IBD patients (122 Crohns disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. RESULTS TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm). CONCLUSION TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.