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      Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes

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          Abstract

          Treatment response to methotrexate (MTX) for rheumatoid arthritis (RA) is not universal and non-adherence may partially explain this. The aims of this systematic review were to: (1) summarise existing rates of adherence to MTX, (2) identify predictors of adherence to MTX, and (3) assess the association between non-adherence and patient outcomes. The authors conducted a systematic search of papers published from January 1980 to February 2015 in PubMed, PsycINFO, EMBASE and CINAHL databases. Studies were eligible for inclusion if: (1) MTX was used as monotherapy or in combination with other therapies, (2) MTX was used in an RA or inflammatory polyarthritis population, (3) adherence was defined and measured as the extent to which patients followed their MTX regimen during the period of prescription, and (4) it was an original piece of research. In total, 10 studies met the inclusion criteria and 8 were evaluated as high quality. Rates of adherence ranged from 59% to 107%, and exposed differences in definitions of adherence, study methodologies and sample heterogeneity. A number of potential predictors of MTX adherence were identified; the strongest being related to beliefs in the necessity and efficacy of MTX, absence of low mood, mild disease and MTX monotherapy. Furthermore, 3 studies tested the association of adherence with disease activity as an outcome measure; all 3 found non-adherence associated with poor treatment response. This systematic review shows the importance of adherence to MTX treatment and summarises the associated modifiable factors.

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          Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.

          Paul Emery, Ferdinand C Breedveld, Stephen D Hall … (2008)
          Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494). 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p 5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups. Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. Wyeth Research.
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            Adherence with statin therapy in elderly patients with and without acute coronary syndromes.

            Cynthia Jackevicius, Muhammad Mamdani, Jack V Tu (2015)
            Landmark clinical trials have demonstrated the survival benefits of statins, with benefits usually starting after 1 to 2 years of treatment. Research prior to these trials of older lipid-lowering agents demonstrated low levels of 1-year adherence. To compare 2-year adherence following statin initiation in 3 cohorts of patients: those with recent acute coronary syndrome (ACS), those with chronic coronary artery disease (CAD), and those without coronary disease (primary prevention). Cohort study using linked population-based administrative data from Ontario. All patients aged 66 years or older who received at least 1 statin prescription between January 1994 and December 1998 and who did not have a statin prescription in the prior year were followed up for 2 years from their first statin prescription. There were 22,379 patients in the ACS, 36,106 in the chronic CAD, and 85,020 in the primary prevention cohorts. Adherence to statins, defined as a statin being dispensed at least every 120 days after the index prescription for 2 years. Two-year adherence rates in the cohorts were only 40.1% for ACS, 36.1% for chronic CAD, and 25.4% for primary prevention. Relative to the ACS cohort, nonadherence was more likely among patients receiving statins in the chronic CAD (relative risk [RR], 1.14; 95% CI, 1.11-1.16) and primary prevention cohorts (RR, 1.92; 95% CI, 1.87-1.96). Elderly patients with and without recent ACS have low rates of adherence to statins. This suggests that many patients initiating statin therapy may receive no or limited benefit from statins because of premature discontinuation.
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              Helping patients follow prescribed treatment: clinical applications.

              A Garg, R. Brian Haynes, H. McDonald (2002)
              Low adherence to prescribed medical regimens is a ubiquitous problem. Typical adherence rates are about 50% for medications and are much lower for lifestyle prescriptions and other more behaviorally demanding regimens. In addition, many patients with medical problems do not seek care or drop out of care prematurely. Although accurate measures of low adherence are lacking for many regimens, simple measures, such as directly asking patients and watching for appointment nonattendance and treatment nonresponse, will detect most problems. For short-term regimens (< or =2 weeks), adherence to medications is readily achieved by giving clear instructions. On the other hand, improving adherence to long-term regimens requires combinations of information about the regimen, counseling about the importance of adherence and how to organize medication taking, reminders about appointments and adherence, rewards and recognition for the patient's efforts to follow the regimen, and enlisting social support from family and friends. Successful interventions for long-term regimens are all labor-intensive but ultimately can be cost-effective.
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                Author and article information

                Journal
                Journal ID (nlm-ta): RMD Open
                Journal ID (iso-abbrev): RMD Open
                Journal ID (hwp): rmdopen
                Journal ID (publisher-id): rmdopen
                Title: RMD Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2056-5933
                Publication date Collection: 2016
                Publication date (Electronic): 20 January 2016
                Volume: 2
                Issue: 1
                Electronic Location Identifier: e000171
                Affiliations
                [1 ]NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester , Manchester, UK
                [2 ]Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester , Manchester, UK
                [3 ]Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester , Manchester, UK
                Author notes
                [Correspondence to ] Dr Suzanne MM Verstappen; suzanne.verstappen@ 123456manchester.ac.uk

                HFH and JB are joint first authors.

                Author information
                http://orcid.org/0000-0002-4834-6719
                Article
                Publisher ID: rmdopen-2015-000171
                DOI: 10.1136/rmdopen-2015-000171
                PMC ID: 4731843
                PubMed ID: 26848403
                SO-VID: 3daafc09-5b64-496d-8dd7-65bcb77d5256
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
                License:

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 13 August 2015
                Date revision received : 23 November 2015
                Date accepted : 26 November 2015
                Categories
                Subject: Rheumatoid Arthritis
                Subject: 1506
                Series title: Original article

                Keywords: rheumatoid arthritis,methotrexate,dmards (synthetic),epidemiology
                Data availability:
                Keywords: rheumatoid arthritis, methotrexate, dmards (synthetic), epidemiology

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