Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis)
Conditions
Interventions
Addition of methotrexaat to anti-therapy (infliximab or adalimumab) according
to standard care (first 12 weeks 25 mg/week, followed by 15 mg/week) or a lower
methotrexaat dosing regime (first 12 wee
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age >= 18 years (both men and women) - Confirmed diagnosis of CD or UC by endoscopy and histopathology - Maintenance therapy with IFX or ADL, with or without thiopurines (i.e. azathioprine or mercaptopurine) - Loss of response, defined by clinical parameters (i.e. HBI >4 points (CD), SCCAI >5 points (UC), and/or patients with actively draining perianal fistula (CD)) and/or with elevated inflammatory biomarkers (i.e. serum CRP >=5 mg/l and/or fecal calprotectin >=250 mg/kg)) - Detectable anti-drug antibodies (ADA) directed against IFX or ADL (>=12 AU/ml) using a drug-sensitive assay - Sub-therapeutic IFX or ADL serum levels (IFX
Exclusion criteria
Exclusion criteria: - Prior intolerance to MTX - Pregnancy or planned pregnancy in the coming year (men and women) - Patients with total bilirubin, alkaline phosphatase, gamma-glutamyl transferase, AST or ALT of more than 2 times the upper limit of normal - Subjects with evidence of or suspected liver disease, such as primary sclerosing cholangitis or cirrhosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A composite primary endpoint will be used: i.e. percentage of patients with: • Complete disappearance of measurable ADA, AND • Measurable IFX or ADL serum concentrations within 6 months after starting MTX | — |
Secondary
| Measure | Time frame |
|---|---|
| - Association of intracellular MTX-Glu1-5 concentrations in red blood cells (RBCs) with reduction of immunogenicity - Association of intracellular MTX-Glu1-5 concentrations in peripheral blood mononuclear cell (PBMCs) with reduction of immunogenicity - Association of plasma MTX concentrations (extracellular concentrations) with reduction of immunogenicity - Correlation of MTX-Glu-1-5 levels between RBCs and PBMCs - Impact of HLA genotype on therapeutic effect of MTX - Time to disappearance of ADA after addition of MTX - Time to regained clinical and biochemical response after addition of MTX - Proportion of patients in clinical remission at week 2, 6, 10, 14, 18, 22 and 26(defined by HBI | — |
Countries
Netherlands
Outcome results
None listed