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



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.



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.



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.
From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland. jcurtis@uab.edu.|J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine. jcurtis@uab.edu.
Jeffrey R
JR
Curtis
From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland.|J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine.
Vivian P
VP
Bykerk
From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland.|J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine.
Maher
M
Aassi
From the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York; Rheumatology Division, University of Colorado School of Medicine, Greenwood Village, Colorado, USA; Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada; F. Hoffmann-La Roche Ltd., Basel, Switzerland.|J.R. Curtis, MD, MS, MPH, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; V.P. Bykerk, MD, Inflammatory Arthritis Center, Hospital for Special Surgery, and Department of Rheumatology, Mount Sinai Hospital; M. Aassi, MD, F. Hoffmann-La Roche Ltd.; M. Schiff, MD, Rheumatology Division, University of Colorado School of Medicine.
Michael
M
Schiff
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D055118:Medication Adherence; D008727:Methotrexate / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D008727:Methotrexate
METHOTREXATE; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; RHEUMATOID ARTHRITIS; RISK FACTORS