The effective management of chronic rheumatic diseases is largely dependent on adherence to treatment with disease-modifying antirheumatic drugs (DMARDs). Nonadherence to these therapies is associated with higher levels of chronic disease activity, greater risk of disease flares, and higher cost and utilization of healthcare resources.1-6
Adherence rates for DMARD treatment are often lower than would be expected. Although studies report rates of nonadherence that are extremely varied, ranging from 3% to 76% in systemic lupus erythematosus (SLE)7 and 14% to 80% in rheumatoid arthritis (RA),8 the actual incidence of nonadherence in the management of rheumatic disease has not been well captured. In their 2015 review of current therapies, Marengo and Suarez-Almazor8 wrote that “despite the clinical importance of suboptimal medication adherence, adherence behaviors are not systematically considered in clinical practice.” They further observed that changes in patient attitudes toward treatments over time are not monitored. These undisclosed patterns of nonadherence contribute to inaccurate evaluations of the efficacy of therapy and undermine progress toward treatment outcomes.
Current Treatment Recommendations
The most commonly used “treat-to-target” drug strategies for rheumatic diseases are designed to achieve remission or significantly reduce disease activity by manipulating doses and by combining or switching therapies. Standard DMARDs or newer biological DMARDS can effectively reduce symptoms and slow disease progression, resulting in better long-term outcomes for patients with RA, while nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids can be used for management of pain and joint swelling.9,10
Patterns of Nonadherence
Unintentional nonadherence is common and is generally due to forgetfulness, a lack of understanding of recommendations, or concomitant illnesses or events. A 2011 study by Daleboudt et al 11 of 106 patients with SLE found that while the overall rate of adherence to immunosuppressive therapies was 86.7%, the majority (58.5%) reported occasional unintentional nonadherence, and possibly more significantly, 46.2% reported occasional intentional nonadherence.
Predictors of Nonadherence
Daleboudt and colleagues also reported that, although disease status appeared to have little impact on adherence to therapies, patients who were more emotionally affected by their disease had more episodes of nonadherence of all types.11
A 2017 investigation by Ahluwalia et al1 looked more closely at predictors of nonadherence in a large observational cohort of 1762 patients with RA (80% women) in Ontario, Canada. The overall rate of nonadherence to any antirheumatic medication in this cohort was 23% (n=409), including 9.4% among those taking DMARD therapies. Patients who were rheumatoid factor positive and those with higher numbers of comorbidities had lower adherence to treatment in this trial; this finding is consistent with previous studies.12-16
The investigators also observed that patients were more likely to discontinue taking antirheumatic medications if they were concomitantly using NSAIDs.1
Among socioeconomic features, marital status had the highest impact on adherence: single, widowed, or divorced status was significantly more predictive of low adherence than being married. “Our results showed that having a family connection (eg, being married) helps to reduce nonadherence in patients,” Dr Ahluwalia said in an interview with Rheumatology Advisor; he attributed this finding to behavioral and psychological factors already known to affect adherence.
Influence of Physician-Patient Interactions
Patients’ relationships with primary care physicians often influence their adherence to therapeutic regimens. As DMARDS are associated with a large number of side effects, trust in the physician’s judgment is an important factor in a patient’s decision to stay on a medication.17-20 Additionally, patients may deliberately enhance adherence to therapies in order to please their physician.
Strategies for Reducing Nonadherence
Marengo and Suarez-Almazor8 point out that unintentional nonadherence is most often due to forgetting to take a dose or refill a prescription. This is more easily rectified with reminders and follow-ups than intentional nonadherence, which they wrote, “is influenced by the patients’ beliefs about the effectiveness of the healthcare recommendation, their knowledge about the disease and their self-efficacy to achieve proposed health goals. Conceivably, nonadherence is most often multifactorial and therefore, interventions tailored to meet each patient’s needs may be more successful in improving adherence.”
Among these interventions, the provision of educational activities on the disease, treatment, and the consequences of nonadherence to long-term outcomes is often a highly effective measure to encourage adherence. Counseling and supportive interventions can be helpful for patients who have emotional issues related to their disease, and cognitive behavioral programs are valuable for teaching patients to adapt to the needs of their disease and maintain a regular routine with medications.
- Ahluwalia V, Rampakakis E, Movahedi M, et al. Predictors of patient decision to discontinue anti-rheumatic medication in patients with rheumatoid arthritis: results from the Ontario best practices research initiative. Clin Rheumatol, 2017;36(11):2421-2430.
- Pasma A, Schenk CV, Timman R, et al. Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease. Arthritis Res Ther. 2015;17:281
- Waimann CA, Marengo MF, de Achaval S, et al. Electronic monitoring of oral therapies in ethnically diverse and economically disadvantaged patients with rheumatoid arthritis: consequences of low adherence. Arthritis Rheum. 2013;65(6):1421-1429.
- Molina E, Del Rincon I, Restrepo JF, et al. Association of socioeconomic status with treatment delays, disease activity, joint damage, and disability in rheumatoid arthritis. Arthritis Care Res. 2015;67:940-946.
- Harrold LR, Briesacher BA, Peterson D, et al. Cost-related medication nonadherence in older patients with rheumatoid arthritis. J Rheumatol. 2013;40:137-143.
- De Vera MA, Mailman J, Galo JS. Economics of nonadherence to biologic therapies in rheumatoid arthritis. Curr Rheumatol Rep. 2014;16:460.
- Costedoat-Chalumeau N, Pouchot J, Guettrot-Imbert G, et al. Adherence to treatment in systemic lupus erythematosus patients. Best Pract Res Clin Rheumatol. 2013;27:329-340.
- Marengo MF, Suarez-Almazor ME. Improving treatment adherence in patients with rheumatoid arthritis: what are the options? Int J Clin Rheumtol. 2015;10:345-356.
- Wabe N, Lee A, Wechalekar M, McWilliams L, Proudman S, Wiese M. Adherence to combination DMARD therapy and treatment outcomes in rheumatoid arthritis: a longitudinal study of new and existing DMARD users. Rheumatol Int. 2017;37:897-904.
- Feldman CH, Yazdany J, Guan H, Solomon DH, Costenbader KH. Medication nonadherence is associated with increased subsequent acute care utilization among Medicaid beneficiaries with systemic lupus erythematosus. Arthritis Care Res. 2015;67:1712-1721.
- Daleboudt GMN, Broadbent E, McQueen F, Kaptein ADA. Intentional and unintentional treatment nonadherence in patients with systemic lupus erythematosus. Arth Care Res. 2011;63:342-350.
- Mjaavatten MD, Radner H, Yoshida K, et al. Inconsistent treatment with disease modifying antirheumatic drugs: a longitudinal data analysis. J Rheumatol. 2014;41:2370-2378. 20-23.
- Park DC, Hertzog C, Leventhal H, et al. Medication adherence in rheumatoid arthritis patients: older is wiser. J Am Geriatr Soc. 1999;47:172-183.
- Tuncay R, Eksioglu E, Cakir B, Gurcay E, Cakci A. Factors affecting drug treatment compliance in patients with rheumatoid arthritis. Rheumatol Int. 2007;27:743-746.
- 15. de Thurah A, Nørgaard M, Johansen MB, Stengaard-Pedersen K. Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease activity, disease duration, and comorbidity in a 10-year longitudinal study. Scand J Rheumatol. 2010;39:197-205.
- Borah BJ, Huang X, Zarotsky V, Globe D. Trends in RA patients’ adherence to subcutaneous anti-TNF therapies and costs. Curr Med Res Opin. 2009;25:1365-1377.
- Costedoat-Chalumeau N, Houssiau F, Izmirly P, et al. A prospective international study on adherence to treatment in 305 patients with flaring systemic lupus erythematosus: assessment by drug levels and by self-questionnaires [published online September 19, 2017]. Clin Pharmacol Ther. doi: 10.1002/cpt.885.
- Bensing JM, Dronkers J. Instrumental and affective aspects of physician behavior. Med Care. 1992;30:283-298.
- van Dulmen S. The key to good healthcare communication. Patient Educ Couns. 2002;46:233-234.
- Simpson M, Buckman R, Stewart M, et al. Doctor-patient communication: the Toronto consensus statement. BMJ. 1991;303:1385-1387.