https://orcid.org/0000-0001-7179-4475
Abstract
Background
Non-adherence to medication (range 30–107%) is a major issue in patients with rheumatoid arthritis (RA). Previous research has shown that electronic monitoring feedback (EMF) might be an effective strategy to improve medication adherence in chronic conditions. Therefore, this study investigated the effectiveness of electronic monitoring feedback in patients with early RA to improve medication adherence and clinical outcomes compared to usual care.
Methods
An open-label randomized clinical trial was performed to compare EMF with standard care during a 12-month follow-up period on two sites of the Sint Maartenskliniek (Nijmegen and Boxmeer) in the Netherlands. Patients were eligible if they: (1) had a (working) diagnosis of early RA, (2) were currently using methotrexate, (3) were aged ≥18 years, and (4) had a life expectancy of ≥12 months. Primary outcome was the difference in proportion of non-adherent patients measured with the Compliance Questionnaire on Rheumatology after 12 months. Secondary outcomes were beliefs about medicines, medication adherence measured with the MMAS-8®, patients' health status, prescription of biologic DMARDs, and disease activity after 12 months.
Results
Of the 367 initially-invited patients, 93 patients with early RA agreed to participate in this study. No significant difference was found in the proportion of non-adherent patients between the intervention arm and the usual care arm after 12 months follow-up (60.0% and 61.3%, p=0.93, respectively). Patients in the intervention arm tended to discontinue methotrexate earlier than patients in the usual care arm (median time in weeks: 15.7 (9.1–33.6) and 21.9 (19–28.4), respectively, p=0.31), whereas patients in the usual care arm tended to initiate biologic DMARDs earlier than those in the intervention arm (median time in weeks: 11.9 (5.7–22) and 17 (9.9–40.9), respectively, p=0.55).
Conclusion
This study illustrates the challenge of targeting non-adherence with EMF in patients with early RA and shares important lessons learned about designing adherence intervention trials with respect to study attrition, accounting for drug survival, intervention fidelity, intervention uptake, and technical aspects.
Abbreviations
ACR, American College of Rheumatology; Anti-CCP, Anti-cyclic citrullinated peptide; BECCI, Behavior Change Counselling Index; bDMARD(s), Biologic disease-modifying antirheumatic drug(s); BMQ, Beliefs about Medicines Questionnaire; CONSORT, Consolidated Standards of Reporting Trials; CQR, Compliance Questionnaire on Rheumatology; DAS28-CRP, Disease Activity Score based on 28 joints and using C-reactive protein; DMARD(s), Disease-modifying antirheumatic drug(s); EMERGE, ESPACOMP Medication Adherence Reporting Guideline; EMF, Electronic monitoring feedback; EULAR, European League Against Rheumatism; HAQ, Health Assessment Questionnaire; HAQ-DI, Health Assessment Questionnaire Disability Index; MEMS®, Medication Event Monitoring System®; MMAS-8®, Morisky Medication Adherence Scale®; NCD, Necessity–concerns differential; RA, Rheumatoid arthritis.
Data Sharing Statement
All data generated or analyzed during this study are included in this published article and its supplementary information files.
Ethics Approval and Consent to Participate
This study was conducted according to the ethical principles for medical research as stated in the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, 2013). The research protocol was submitted for consideration, comment, guidance and approval to the Medical Research Ethics Committee (MREC) of Arnhem-Nijmegen before the study began. The MREC of Arnhem-Nijmegen waived official ethical approval (file number: 2014-137) and assessed the trial as not being subject to the Medical Research Involving Human Subjects Act (WMO). Providing electronic monitoring feedback in addition to standard care was not considered an infringement of the physical and/or psychological integrity of the subject. All study participants provided written informed consent before inclusion in this study. Patient data were handled according to the applicable laws and regulations. A document that linked the study codes to the patients’ identifying information was digitally stored and protected.
Principal Investigator Statement
The authors confirm that the PI for this paper is BJF van den Bemt and that he had direct clinical responsibility for patients.
Trial Registration
Netherlands Trial Register: Trial NL4532 (old NTR ID 4667, date registered July 3, 2014), https://www.trialregister.nl/trial/4532.
Acknowledgments
The authors would like to thank all patients who participated in this study, as well as the healthcare professionals involved in this study. Special thanks are extended to the patient research partners for their assistance in the design phase of the study.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
Dr Milou van Heuckelum reports receipt of grants from the Dutch Arthritis Foundation during the conduct of the study and grants from the Dutch Arthritis Foundation outside the submitted work. The authors reported no other potential conflicts of interest in this work.