Background Non-adherence to conventional DMARDs is an important indicator for the effectiveness of treatment in early arthritis patients. Reported non-adherence rates differ widely, because studies use different adherence measures.
Objectives This study compared three methods to ascertain how non-adherence should be measured: a validated self-report questionnaire: the Compliance Questionnaire Rheumatology (CQR), the intracellular uptake of methotrexate (MTX) in the form of methotrexate-polyglutamates (MTXPGs) and the electronic measurement of adherence with Medication Event Monitoring Systems (MEMS).
Methods Adult patients diagnosed with inflammatory arthritis who started DMARDs were included in a cohort study. MTXPGs were collected and the CQR was filled out after 3, 6, 9 and 12 months of treatment. Non-adherence was continuously measured with MEMS. When there was a discordance between the observed opening and the expected opening of the MEMS cap, this was assigned as a non-adherence event. Relations of MEMS non-adherence proportion with CQR score and MTXPGs were determined with Spearman rank correlations. Sensitivity and specificity of respectively the CQR score against a MEMS 83% (minimum two weeks of non-adherence) cut-off score was calculated at 3, 6, 9 and 12 months. The same applied to the MTX-PGs against a MEMS 84% cut-off score and the MTXPGs against a CQR cut-off score. To assess the influence of adherence measured with MEMS on MTXPGs, an univariate and multivariate linear regression (backward selection, criterion for deletion p>0.10) with MTXPGs as dependent variable and with non-adherence measured with MEMS the 12 weeks before MTXPG measurement (continuous score), age, gender, time of treatment and dosage as independent variables was performed.
Results Two hundred and one patients entered the study. As measured with MEMS, non-adherence rates varied over time and between different DMARDs (figure 1). For sulfasalazine and hydroxychloroquine, the non-adherence rates were highest. For all medicines, except for prednisone, the non-adherence rate rose over time. The CQR did only weakly correlate (-0.255) with the MEMS non-adherence proportion at 9 months of therapy and was not associated with MTXPGs. Only at 9 months and 12 months, the ROC curves showed some discrimination between non-adherence measured with MEMS against the CQR score. Non-adherence (β -28,3, p=0.078), time of treatment in weeks (β 1.5, p<0.00) and age (β 1.83, p<0.00) contributed to MTXPGs at 12 months.
Conclusions Non-adherence percentages for all DMARDs rise over time, except for prednisone. This might be explained by the fact that patients immediately experience the effect of prednisone, and that most patients tapered prednisone. The CQR is only slightly associated with MEMS after T2 and not at all with MTXPGs. A stronger relationship between these 2 measurement methods was expected. The relatively low relationship may be related to individual differences in the uptake of MTX. We have to learn more about the uptake of MTX over time per patient, before we can use MTXPGs in daily practice as a non-adherence measure.
Disclosure of Interest None declared
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