ADMETTRE MTX-studie: therapietrouw (ADherentie) aan laaggedoseerd METhoTRExaat in kinderen met juveniele idiopathische artritis gebruikmakend van een gevoelige MethoTreXaat analysemethode

ADMETTRE MTX-study: ADherence to low-dose METhoTRExate in children with juvenile idiopathic arthritis using a sensitive Metho TreXate assay Background Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis (JIA). Unfortunately, a substantial part of patients has insuf- ficient efficacy of MTX. A potential cause of this inad- equate response is suboptimal drug adherence. Besides, adherence numbers from literature could be overestimated with the commonly used methods, like questionnaires. Objective The aim of this study was to assess MTX adherence in JIA patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined. Design This was a retrospective, observational study using plasma samples from JIA patients stored in the Phar- machild biobank of the Wilhelmina Children's Hospital. Methods An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantifica- tion of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in JIA patients were compared with corresponding adherence limits, categorising them as either adher- ent or possibly non-adherent to MTX therapy. Results Plasma samples of 43 patients with JIA were anal- ysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (P=0.002). No associ- ation was found between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (P1.00 and P = 0.27, respectively; Fisher's Exact). Conclusion Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physi- cians to refute or support suspicion of non-adherence to MTX therapy.