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

Abstract

Objective.Medication adherence in patients with rheumatoid arthritis (RA) is typically suboptimal. Nonadherence has been associated with symptom worsening and increased disability. We systematically reviewed published clinical studies to evaluate methotrexate (MTX) adherence and persistence, factors associated with MTX adherence and persistence, and the effect of MTX nonadherence on clinical outcomes in RA.Methods.MEDLINE and Embase were systematically searched (inception to February 2016) using relevant keywords. Observational or interventional clinical studies in patients with RA that specifically reported adherence to or persistence with MTX were included. Data were extracted using a predesigned, standardized template that included study design, patient demographics, and relevant outcomes. Main outcomes were MTX adherence and persistence rates in patients with RA treated with MTX and factors associated with MTX adherence and persistence.Results.Of 365 references screened, 31 articles met inclusion criteria and another 10 were identified from searching reference lists. Estimates of MTX adherence varied from study to study because of heterogeneity in patient populations, duration of followup, definitions of adherence, and methods of assessment. Rates of MTX persistence ranged from 50% to 94% at 1 year and 25% to 79% at 5 years. No clear trends were identified in factors that influence MTX adherence and persistence. Two studies suggested that MTX adherence was associated with superior clinical outcomes.Conclusion.MTX adherence and persistence are highly variable in patients with RA. Research is necessary to determine the effect of nonadherence on health outcomes and to identify independent predictors of nonadherence to inform evidence-based interventions.

Mobile Phone Text Messages and Effect on Treatment Adherence in Patients Taking Methotrexate for Rheumatoid Arthritis: A Randomized Pilot Study

“…According to studies of adherence with MTX treatment, age, family status (divorce), psychological disorders, ethnic origin, disease activity, MTX dosage, and potential toxicity are associated with poor adherence, although discordant results have been reported for most of these factors . We found that nonadherent patients had a higher level of disease activity at baseline (with a higher DAS28 and a lower HAQ score).…”

“…(33%), the lack of a perceived need for treatment (24%), and worries about adverse effects (24%) . In addition to nonadherence, the 1‐year nonpersistence rate for MTX is high (50%) .…”

Rheumatologists' insight into medication adherence in patients with rheumatoid arthritis: A qualitative study

“…[6][7][8] A systematic review of quantitative studies examining determinants of adherence in patients with RA found that adherence rates are highly variable and there is no consistency in determinants of non-adherence. 9 Due to the complex nature of medication adherence, qualitative studies have the potential to provide a more robust understanding of this phenomenon. 10 Qualitative studies published to date addressing determinants of adherence in people with RA have mainly targeted patients' perspectives.…”

Real‐World Adherence to Oral Methotrexate Measured Electronically in Patients With Established Rheumatoid Arthritis

“…Our results showed that MTX adherence gradually decreased over time, even though the majority of patients took it correctly during the overall adherence period (75%) and during the implementation period (80%). Rates of MTX adherence vary across studies depending on a variety of factors, including the definition of adherence and the method of measurement used . For example, in claims‐based studies of real‐world data, adherence varied from 80% (MTX monotherapy) and 64% to 72% (MTX combination therapy) when measured by medication possession ratio and from 36% to 50% (csDMARDs, including MTX, prescribed with bDMARDs) when measured by prescriptions of csDMARDs filled .…”

“…The current treatment guidelines for RA also recommend the concomitant administration of MTX with biologic DMARDs (bDMARDs) , as prior evidence has shown that the efficacy and drug survival of bDMARDs are increased when given in combination with MTX vs monotherapy . Although MTX use is common, patients may experience adverse events (up to 45%) or inadequate efficacy, which may influence treatment adherence .…”