Background Methotrexate (MTX) is a cornerstone therapy and common first-line drug for patients with rheumatoid arthritis (RA), worldwide. However, there is significant variability in patients' response to MTX, both in efficacy and toxicity. It has been hypothesized that this finding may be partially explained by non-adherence to MTX.
Objectives The aims of this study were to assess patients' self-reported adherence to MTX and to identify factors associated with non-adherence.
Methods In the period between November 1 and December 15, 2015, 315 consecutive RA patients who were treated in one of three randomly chosen Serbian clinics were enrolled in cross-sectional study. The inclusion criteria were: age ≥18 years, diagnosis of RA of at least 6 months, current MTX use for at least 1 month (with or without concomitant usage of another RA drugs), and written informed consent. The associations between investigated demographic and clinical characteristics of the patients and non-adherence to MTX were assessed applying univariate logistic regression analysis. Furthermore, baseline variables with a significant association with non-adherence in univariate logistic regression analysis (defined as p<0.05) were entered into a multivariate logistic regression equation to identify independent predictors of non-adherence to MTX.
Results Study population was predominantly female (74.0%), and the average current age was 56.0±12.5 years. The median duration of RA was 8 years, while the median duration of MTX treatment was 5 years. The majority of the patients (82.2%) reported using the oral formulation of MTX. The median maximum dose of MTX which responders received was 15 mg per week. Most of the participants in our survey stated that MTX was well tolerated, while 20% of RA patients reported poor tolerance. The overall prevalence of non-adherence to MTX was 24.8%. Forgetting to take medication (43.7%) was the most commonly-reported reason for MTX non-adherence. According to the results of univariate regression analysis the following factors are significantly associated with non-adherence to MTX: younger age (OR=0.963; p<0.001), employment (OR=1.859; p=0.029), poor self-reported MTX tolerance (OR=1.289; p=0.041), laboratory blood analyses performed less than once in three months (OR=2.170; p=0.043) and concomitant use of biological therapy (OR=2.312; p=0.002). Finally, in the multivariate regression model the following variables remained statistically significant and were identified as independent predictors of non-adherence to MTX: younger age (OR=0.969; p=0.006), laboratory blood analyses performed less than once in three months (OR=2.735; p=0.015) and concomitant use of biological therapy (OR=2.067; p=0.017).
Conclusions The results of our study have shown that about one forth of RA patients met the criteria for non-adherence to MTX. Identification of vulnerable groups who are likely to be non-adherent to MTX has practical implications in identifying the patients who would benefit from alternative RA treatments and, would present an opportunity for timely intervention and optimization of treatment response.
Disclosure of Interest N. Damjanov: None declared, J. Nedovic: None declared, M. Lazarevic: None declared, S. Mamula Masic Grant/research support from: provided by Roche d.o.o., Employee of: Roche d.o.o.