Infliximab for Ulcerative colitis|Crohn's disease

Inclusion criteria

• {"criterion_text":"- For patients with ulcerative colitis: • Diagnosis: Ulcerative colitis • Age 18-80 years. • Male or female. • IFX or ADA treatment since >12 months; last 3 doses at the same dose and interval. If the patient is on a biosimilar-infliximab the patient must have received at least 3 doses, and at the same dose and interval. • SCCAI score of ≤3. • Endoscopic Baron score of 0-1. The most inflamed part in the rectum/ sigmoid colon is evaluated. A minimum of 40 cm of the colon should be examined."}
• {"criterion_text":"- For patients with Crohn's disease: • Diagnosis: Crohn's disease • Age 18-80 years. • Male or female. • IFX or ADA treatment since >12 months; last 3 doses at the same dose and interval. If the patient is on a biosimilar-infliximab the patient must have received at least 3 doses, and at the same dose and interval. • Simplified HBI (sHBI; abdominal palpation excluded) score of ≤4. • Simplified Endoscopic Score for CD (SES-CD) of ≤4 and no ulcer ≥5 mm other than a potential anastomotic ulcer (ie apthous ulcers allowed). • F-calprotectin <200 mg/kg (PhiCal) or <350 mg/kg (Buhlmann)."}

Exclusion criteria

• {"criterion_text":"- Pregnancy"}
• {"criterion_text":"- Corticosteroid (rectal or systemic) or rectal 5-ASA treatment during the last 6 months."}
• {"criterion_text":"- For patients with ulcerative colitis: Colonic resection."}
• {"criterion_text":"- For patients with Crohn's disease: Documented engagement/inflammation of the small bowel proximally of a level of 50 cm from the ileocecal valve. Any examination modality is accepted, and a current/new small intestinal examination is not required. A limited number of small (<5 mm) lesions on capsule endoscopy allowed. Colonic surgery with removal of more than half of the transverse colon."}

Primary endpoints

• {"endpoint_text":"- The proportion of patients that relapses, as defined by symptomatic scoring in combination with endoscopy, at 12 and 24 months after discontinuation of anti-TNF treatment with identification of factors at study-start that correlate positively or negatively with the event of relapse.","definition_or_measurement_approach":"Relapse defined by symptomatic scoring in combination with endoscopy, assessed at 12 and 24 months after discontinuation; baseline factors correlated with relapse outcome."}

Secondary endpoints

• {"endpoint_text":"- Endoscopic scores at 12 and 24 months among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Endoscopic scoring performed at 12 and 24 months; comparison between relapsed and non-relapsed participants."}
• {"endpoint_text":"- Fecal calprotectin levels at 12 and 24 months among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Fecal calprotectin measured at 12 and 24 months; group comparison."}
• {"endpoint_text":"- Fecal calprotectin levels at study start among ulcerative colitis patients who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Baseline fecal calprotectin measurement in UC patients compared between those who later relapse and those who remain in remission."}
• {"endpoint_text":"- The rate of relapse among ulcerative colitis patients with the following fecal calprotectin level ranges (<30 mg/kg for Calpro [C] and <60 mg/kg for Buhlmann [B]; 30-99 mg/kg C and 60-199 mg/kg B; 100-299 mg/kg C and 200-599 mg/kg B; ≥300 mg/kg C and ≥600 mg/kg B.","definition_or_measurement_approach":"Relapse rates stratified by predefined fecal calprotectin ranges for two assay types (Calpro and Buhlmann)."}
• {"endpoint_text":"- The optimal fecal calprotectin level cut-off with regards to sensitivity and specificity for relapse, for ulcerative colitis and Crohn's disease patients, respectively.","definition_or_measurement_approach":"ROC/diagnostic performance analysis to determine optimal fecal calprotectin cut-offs for predicting relapse in UC and CD."}
• {"endpoint_text":"- Trough concentrations of infliximab and adalimumab among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Measure drug trough concentrations; compare levels between relapsed and non-relapsed participants."}
• {"endpoint_text":"- The rate of relapse among those with undetectable infliximab or adalimumab trough concentrations, those with 0.5-2.9 ug/ml, 3.0-7.0 ug/ml, >7.0 ug/ml for infliximab, and ≥10.0 ug/ml for adalimumab.","definition_or_measurement_approach":"Relapse rates stratified by predefined drug trough concentration categories for infliximab and adalimumab."}
• {"endpoint_text":"- The optimal trough concentration cut-off with regards to sensitivity and specificity for relapse, for infliximab and adalimumab, respectively.","definition_or_measurement_approach":"ROC/diagnostic performance analysis to determine optimal trough concentration cut-offs predictive of relapse for each drug."}
• {"endpoint_text":"- Area under the infliximab or adalimumab concentration curve during the last therapy cycle among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Calculate AUC of drug concentration during last therapy cycle; compare AUC between relapsed and non-relapsed groups."}
• {"endpoint_text":"- Presence of anti-drug antibodies among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Assess anti-drug antibodies and compare prevalence between relapsed and non-relapsed participants."}
• {"endpoint_text":"- The rate of relapse among those with anti-drug antibodies versus those without.","definition_or_measurement_approach":"Compare relapse rates between participants positive versus negative for anti-drug antibodies."}
• {"endpoint_text":"- Time to relapse among those who relapse, comparing ADA versus IFX treated and UC versus CD.","definition_or_measurement_approach":"Time-to-event analysis (time to relapse) with subgroup comparisons by drug (adalimumab vs infliximab) and disease (UC vs CD)."}
• {"endpoint_text":"- The level of gut microbiota dysbiosis among those who relapsed compared to those who remained in remission.","definition_or_measurement_approach":"Assess gut microbiota dysbiosis scores; compare between relapsed and non-relapsed participants."}
• {"endpoint_text":"- The rate of relapse among those with a dysbiosis score of 1, 2-3, and 4-5, respectively.","definition_or_measurement_approach":"Relapse rates stratified by predefined dysbiosis score categories."}
• {"endpoint_text":"- Correlation analyses of genes showing high versus low expression in mucosal biopsies and blood samples, with the event of relapse.","definition_or_measurement_approach":"Gene expression correlation analyses in mucosal biopsies and blood samples versus relapse outcome."}
• {"endpoint_text":"- Correlation analyses of gene-variants with the event of relapse.","definition_or_measurement_approach":"Genetic variant association analyses with relapse outcome."}
• {"endpoint_text":"- Additional factors that will be correlated with relapse rates: Endoscopic scores; corticosteroid use between 12 and 6 months before baseline; previous anti-TNF treatment; dose intensification of anti-TNF treatment; mono- versus concomitant immunomodulatortreatment; previously maximal inflammatory extent (Montreal classification); disease duration; extraintestinal manifestations; gender; smoking; hemoglobin; white blood cell count; platelet count; CRP; and histology/immunohistochemistry.","definition_or_measurement_approach":"Correlation analyses of listed clinical, laboratory and histologic factors with relapse rates."}

Sweden

Earliest CTIS Part Ii Submission Date

15-08-2024

Latest Decision Or Authorization Date

09-09-2024

Processing Time Days

25

Number Of Sites

4

Number Of Participants

350

Primary sponsor

Full Name

Region Skane

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden