METHOTREXATE for Crohn's disease

Inclusion criteria

• {"criterion_text":"- Age of 4-28 years\n- Written informed consent of patient (if indicated) and parents (if indicated) has been obtained\n- Proven diagnosis of Crohn’s disease based on endoscopic, radiological and histologic findings\n- Will start MTX treatment monotherapy or combination therapy with infliximab"}

Exclusion criteria

• {"criterion_text":"- Not eligible to receive MTX, as in usual care\n- Co-treatment with a biologic agent other than infliximab\n- Inability to read and understand the patient and family information sheets\n- Informed consent of patient has not been obtained when required"}

Primary endpoints

• {"endpoint_text":"- [PK] RBC MTX-PG levels at 1,3 and 6 months [PD] Drug survival; defined as the cumulative incidence of MTX monotherapy discontinuation during the first year due to treatment failure and/or toxicity. Treatment failure includes need for systemic corticosteroids, biologicals, JAK inhibitors, thiopurine therapy and/or surgery due to CD inflammation because of a flare of CD. Locally applied corticosteroids or dose escalation of MTX will not be considered as treatment failure.","definition_or_measurement_approach":"[PK] Determination of MTX-PG concentrations in red blood cells (RBCs) measured at 1, 3 and 6 months and identification of accumulation patterns over time. [PD] Drug survival measured as the cumulative incidence of MTX monotherapy discontinuation during the first year due to treatment failure and/or toxicity; treatment failure is defined as need for systemic corticosteroids, biologicals, JAK inhibitors, thiopurine therapy and/or surgery for active Crohn's disease. Locally applied corticosteroids or MTX dose escalation are not considered treatment failure."}

Secondary endpoints

• {"endpoint_text":"- -Sex -Age -Weight -Length -BMI -Body Surface Area (BSA) -Smoking status; including vaping and parental smoking status -Extra-intestinal manifestations -Comorbidity -Previous IBD medication -Co-medication - Renal function -MTX dose -Route of administration of MTX -Folic acid dose -Adherence\n- PBMC MTX-PG levels at 1,3,6 months (academic hospitals) and RBC MTX-PG levels at 1,3 and 6 months\n- -DNA SNP’s -FPGS activity -Transcriptome-wide RNA sequencing -Plasma cotinine (µg/L) -Erythrocyte folate (nmol/L) -Plasma homocysteine (µmol/L) -Plasma metabolomics\n- -Faecal microbiome -Faecal metabolome\n- - Drug survival due to treatment failure -Disease activity scores at baseline, 1,3,6 and 12 months -Faecal calprotectin at baseline, 1,3,6 and 12 months - CRP at baseline 1,3,6 and 12 months - SIBDQ at baseline, 1,3,6 and 12 months\n- - Drug survival; Defined as the cumulative incidence of MTX monotherapy discontinuation during the first year due to toxicity. -Whole blood count (CBC) at 1,3,6,12 months *routine -Liver blood test at 1,3,6,12 months *routine - MISS questionnaire at 1,3,6 and 12 months and if patients stop MTX treatment (tolerance defined as <6)\n- Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and efficacy.\n- Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and toxicity.\n- Infliximab dose - Route of administration of infliximab -Infliximab induction and maintenance schedule\n- Infliximab levels *routine\n- Anti-drug-antibodies to infliximab *routine","definition_or_measurement_approach":"Secondary measures include demographic and clinical covariates (sex, age, weight, length, BMI, BSA, smoking status including vaping and parental smoking, extra-intestinal manifestations, comorbidity, previous IBD medication, co-medication, renal function, MTX dose, route, folic acid dose, adherence); PK measures: PBMC and RBC MTX-PG measured at 1,3,6 months (PBMCs at academic hospitals); genetic and metabolic markers (DNA SNPs, FPGS activity, transcriptome-wide RNA sequencing, plasma cotinine, erythrocyte folate, plasma homocysteine, plasma metabolomics); microbiome/metabolome from faeces; clinical outcomes: disease activity scores, faecal calprotectin, CRP, SIBDQ at baseline,1,3,6,12 months; drug survival due to treatment failure and due to toxicity defined as cumulative incidence of MTX monotherapy discontinuation during first year; routine labs (CBC, liver tests) at 1,3,6,12 months; MISS questionnaire at scheduled visits and on stopping MTX."}

Netherlands

Latest Decision Or Authorization Date

05-05-2026

Number Of Sites

2

Number Of Participants

215

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"MDL Fonds","duties_or_roles":"Monetary support","organisation_type":""}