Exposure-response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: A secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT).
Wan M., Jones AP., Maskrey D., Arenas-Hernandez M., Rosala-Hallas A., Beattie PE., Baron S., Browne F., Brown SJ., Gach JE., Greenblatt D., Hearn R., Hilger E., Esdaile B., Cork MJ., Howard E., Lovgren M-L., August S., Ashoor F., Williamson PR., McPherson T., O'Kane D., Ravenscroft J., Shaw L., Sinha MD., Spowart C., Thomas BR., Sach TH., Irvine AD., Flohr C.
This is a secondary analysis of a multicentre randomised controlled trial of ciclosporin and methotrexate in children and young people (CYP) with severe atopic dermatitis (AD). Longitudinal trough ciclosporin and erythrocyte methotrexate polyglutamates (MTX-PG) concentrations were measured to evaluate their associations with treatment response and adverse events. Both ciclosporin (4 mg/kg/day) and methotrexate (0.4 mg/kg/week) led to a significant reduction in disease severity scores over the 36-week treatment period. Higher trough ciclosporin concentrations were associated with lower disease severity scores and may serve as a useful tool for therapeutic drug monitoring of ciclosporin in CYP with AD. However, in contrast to a previously published study, steady-state erythrocyte-MTX-PG concentrations showed no significant association with treatment response. Drug concentrations were comparable between patients with and without drug-related adverse events.