Adherence to Methotrexate in Rheumatoid Arthritis: A Danish Nationwide Cohort Study

Abstract

Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis/contact, with at least one prescription of MTX (L04AX03), were included. Results. A total of 18,703 (47.6%) patients had ever used MTX among 39,286 with a diagnosis of RA; among the MTX users, 16,503 (88.2%) had filed more than one MTX prescription. The median time from diagnosis to first MTX prescription was 0.66 (IQR 0.26–1.80) years. In those who filed more than one MTX prescription, the mean adherence time for ≥7.5 mg MTX per week was 1,925 (IQR 467–3,056) days for patients treated in private practice versus 1,892 (IQR 452–3,316) days for patients treated in hospital. The main determinants of nonadherence were female gender, younger age, and time from diagnosis to initiation of MTX. Conclusions. Treatment at hospital or in private practice did not influence the adherence to MTX. Nonmodifiable factors of importance were gender and age, while adherence to MTX therapy decreased with time lapse between diagnosis and prescription.

Adherence and Persistence with Methotrexate in Rheumatoid Arthritis: A Systematic Review

“…For each study, data were extracted and quality was assessed. Results are summarized in Table 1 9,11,12,19,20,21,22,23,24,25,26,27 , Table 2, Table 3 [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]48,49,50,51,52,53,54,55,56 , and Table 4, as well as Supplementary Table 2 and Supplementary Table 3 (available online at jrheum.org). MTX adherence.…”

“…Two studies indicated no association between biologic use and MTX adherence 12,55 , whereas among patients initiating MTX therapy in a Veterans Affairs registry, a higher proportion of nonadherent patients than adherent patients were treated with concomitant tumor necrosis factor antagonists (p = 0.04) 11 . However, patient numbers were relatively small.…”

“…Persistence with MTX. Twenty-nine studies evaluated persistence with MTX (Table 3) [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]48,49,50,51,52,53,54,55,56 . Most were in the United States and Europe, and 1 each in Israel, India, and Japan.…”

“…However, factors such as disease severity, RA duration, and MTX administration era might have confounded these results 40 . In a study in Japan 45 , where MTX doses are generally lower than in Western countries, multiregression analysis showed that no previous DMARD use (relative to previous DMARD use ≥ 3) was an independent predictor of MTX survival (adjusted RR 2.07, 95% CI Beginning MTX treatment at a later yr 28 Public vs private healthcare 55 Specific rheumatologist 37,42 Disease-related Shorter duration of disease 31,39,47,55 Duration of disease 11,22,30,38,42,45 Age at disease onset 39 Fewer comorbidities 50 Comorbidities 9,22,a More comorbidities 26 Lower ESR 9,11 ESR 30 Higher CRP 22 Seronegativity 32 Autoantibody status 11 Lower disease activity 11,12 Disease activity/severity 28,30,50 Better function 47 Function/disability 9,19,23,30,39 Normal grip strength 30 Better patient's global assessment 47 Pain score 39 No ulcer/mild liver disease 22 Therapy-related MTX monotherapy 9,46 Higher MTX dose 40 MTX dose 23,31,45 Less frequent dosing 19 Administration PO vs IM …”

Non-persistence and non-adherence to MTX therapy in patients with rheumatoid arthritis: a retrospective cohort study based on German RA patients

“… 20 – 23 In line with that, a recent analysis of a Danish nationwide longitudinal cohort of patients hospitalized for RA reported a substantial percentage of >10% of patients to be early MTX therapy discontinuers, defined as no second filled MTX prescription. 24 …”