Introduction: Methotrexate (MTX) reduces rheumatoid arthritis activity and ameliorates the long-term functional status in these patients. To achieve this aim, patients need to take their medication regularly. Nevertheless, non-adherence to MTX still remains a considerable issue in the management of rheumatoid arthritis. Objective: This study aimed to estimate the adherence to methotrexate in patients with rheumatoid arthritis and to identify specific non-adherence risk factors. Methods: A cross-sectional study included 111 patients (mean age 56.2 ± 10.6 years, 78.4% female, and mean disease duration 6 years (3–13)). Three adherence self-assessment questionnaires were used: the Compliance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale, HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% of patients (MARS-5), and 82.9% of patients (VAS questionnaire). All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r = 0.364, r = 0.329, respectively, p < 0.001 for both) and between the VAS and MARS-5 scores (r = 0.496, p < 0.001). A significant positive prediction was shown for urban residence (0.347 (0.134–0.901), p = 0.030) using the MARS-5, female sex (0.264 (0.095–0.730), p = 0.010) according to the CQR19, and for a dose of methotrexate (0.881 (0.783–0.992), p = 0.036) using the VAS, while negative predictions were shown for comorbidity number (3.062 (1.057–8.874), p = 0.039) and depression (1.142 (1.010–1.293), p = 0.035) using the MARS-5 and for older age (1.041 (1.003–1.081), p = 0.034) according to the CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for methotrexate adherence in the multivariate logistic regression. Conclusions: We showed non-adherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

Background/Aim. Rheumatoid arthritis (RA) is accompanied by numerous comorbidities, among which depression and anxiety (D/A) occupy a significant place. The aim of the study was to determine the prevalence of D/A in RA patients and the relationship with their quality of life (QoL). Methods. The study included RA patients treated at the Rheumatology Clinic of the Military Medical Academy in Belgrade, Serbia in the period from May to November 2016. Disease activity was assessed by the Disease Activity Score 28-SE (DAS28-SE). D/A was determined using the Hospital Anxiety and Depression Scale (HADS) questionnaire and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) questionnaire Question 5. Three questionnaires were used to assess QoL: the general RAND 36-item Health Survey 1.0 (RAND36), the specific Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and EQ-5D-3L. Results. Based on the HADS questionnaire, the prevalence of depression was 52% with the average HADS score value of 7.6 +/- 3.2, while the prevalence of anxiety was 32% with the mean HADS score value of 5.8 +/- 3.8. Question 5 of the EQ-5D questionnaire showed that the prevalence of D/A was 77.4%, of which 71.7% of patients had moderate D/ A, while 5.7% of patients had severe D/A. Impairment in all the domains of QoL was found in tested patients, as assessed by all three questionnaires. The RAQoL questionnaire showed moderate QoL impairment, with a score value of 15.5 +/- 7.9. The EQ-VAS score value was 58.6 +/- 16.0, while the EQ-5D index was 0.6 +/- 0.3. Univariate linear regression produced a statistically significant negative predictive value of QoL for the presence of D/A. Multivariate linear regression showed a statistically significant independent negative predictive value of QoL, as assessed by the RAQoL questionnaire (p = 0.010) and the mental QoL component of the RAND 36 questionnaire (p = 0.030) for the degree of depression. Conclusion. In RA patients, there is a significant prevalence of D/A as well as impairment of QoL in all domains. The tests performed have shown that QoL has a statistically significant negative predictive value for the presence of D/A.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by symmetrical peripheral polyarthritis and progressive joint damage. Disease-modifying antirheumatic drugs (DMARDs) reduce disease activity, and radiological progression of the joints, and improve the long-term functional status of patients with RA. The precondition for these positive outcomes is adequate patient adherence to DMARDs. According to the latest EULAR (The European Alliance of Associations for Rheumatology) recommendations, methotrexate (MTX) is still the first-line drug for the treatment of RA. It can be used as monotherapy or in combination with other synthetic or biological DMARDs. Methotrexate is a structural analog of folic acid, which inhibits the de novo synthesis of purines and pyrimidines but acts on inflammation and other mechanisms such as increased release of adenosine, inhibition of the transmethylation reaction, reduced accumulation of polyamines, and separation of nitric oxide synthase. Methotrexate affects the function of almost all cell types involved in inflammation (neutrophils, monocytes, Tand B-cells, endothelial cells, and fibroblast-like synovium). However, not all patients respond well to MTX, which can partly be explained by non-adherence. The adherence rate varies between 59% and 107%, where the overuse of MTX is also an adherence problem. Optimal use of MTX involves starting therapy without delay, following the recommended dose and regimen until a satisfactory response to therapy is achieved, and following the maintenance dose. Over 200 variables influencing adherence have been identified, but none of these variables have been consistently linked in all previous research. Therefore, it is not possible to create a specific risk profile for non-adherence. Considering this fact and the existence of a significant number of non-adherent patients, there is a need to find tailored interventions to improve adherence to MTX in patients with RA that could improve the outcomes of the disease.

Objective: This study aimed to estimate adherence to methotrexate in patients with rheumatoid arthritis and identify specific nonadherence risk factors. Methods: A cross-sectional study included 111 patients (age mean 56.2±10.6 years, 78.4% female, and disease duration mean 6 (3-13) years). Three adherence self-assessment questionnaires were used: the Compli-ance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale- HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% (MARS-5), and 82.9% of patients in the VAS questionnaire. All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r =0.364, r=0.329 respectively, p<0.001 for both), between VAS and MARS-5 score (r=0.496, p<0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p=0.030), using the MARS-5 scale, female sex (0.264 (0.095-0.730), p=0.010) according to CQR19 and for a dose of methotrexate (0.881 (0.783-0.992), p=0.036) in VAS scale, while negative prediction were shown for comorbidity number (3.062 (1.057-8.874), p=0.039), and depression (1.142 (1.010-1.293), p=0.035) using MARS-5 scale and for older age (1.041 (1.003-1.081), p=0.034) according to CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for metho-trexate adherence in multivariant logistic regression. Conclusion: We showed nonadherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.