Methotrexate in paediatric and adolescent Crohn’s disease: an observational study

Condition studied

Crohn’s disease

Investigational medicinal product(s)

Eligibility

Primary endpoint

[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.

Endpoint detail

-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, PBMC MTX-PG levels at 1,3,6 months (academic hospitals) and RBC MTX-PG levels at 1,3 and 6 months, -DNA SNP’s -FPGS activity -Transcriptome-wide RNA sequencing -Plasma cotinine (µg/L) -Erythrocyte folate (nmol/L) -Plasma homocysteine (µmol/L) -Plasma metabolomics, -Faecal microbiome -Faecal metabolome, - 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, - 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), Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and efficacy., Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and toxicity., Infliximab dose - Route of administration of infliximab -Infliximab induction and maintenance schedule, Infliximab levels *routine, Anti-drug-antibodies to infliximab *routine