Improving Medication Adherence With Drug Monitoring in SLE

Poor adherence to medication regimens among patients with systemic lupus erythematosus (SLE) can result in serious consequences, including flares, increased morbidity, higher rates of acute care use, adverse renal outcomes, higher SLE disease activity scores, and poorer quality of life.^1,2

Medication adherence is generally lower in patients with chronic diseases compared with those who have acute conditions.³ Medication adherence in chronic disease tends to worsen over time, with precipitous declines after the first 6 months of treatment.³ Estimates of nonadherence to medication in patients with SLE range from 3% to 76%, depending on methods of measurement and the specific agents being studied.¹

SLE is associated with several characteristics that may make these patients at especially high risk for treatment nonadherence, including cognitive and psychological manifestations, frequently complex treatment regimens, fluctuating symptoms, and a disproportionate prevalence of disease among people of lower socioeconomic status.⁴ A recent study in Medicaid beneficiaries, an especially vulnerable population, found that among 10,406 patients with SLE who had recently initiated hydroxychloroquine, 36% had few or any refills after the first dispensing, and only 17% were adherent for more than 80% of the days over the following year.⁴ Rates of adherence over 80% are typically considered acceptable.²

In another recent study conducted in a cohort of 632 African Americans with SLE, only 16% were highly adherent to their medication regimens, and more than half reported low adherence. Depressive symptoms were significantly associated with nonadherence.⁵ Lead investigator Erica Heiman, MD, of Emory University, Atlanta, Georgia, told Rheumatology Advisor that the study’s results suggest that rheumatologists should consider making mental health issues more central to their practice. “Whether this means screening patients for depression and referring to outside mental health services or working within collaborative practices with on-site mental health providers, our findings really underscore the strong ties between a patient’s mental health and their medication-taking behaviors,” she noted. “The only other variables with significant relationships to medication adherence in our analysis were female sex and younger age. These findings suggest that outreach programs designed to improve patients’ adherence may be most efficient when targeted toward patients with these demographic characteristics.”

Nonjudgmental questioning by clinicians is a practical approach to assessing whether patients are taking their medications as prescribed; however, these conversations frequently fail to elicit the true extent of nonadherence, in part because patients may want to please their providers and tell them what they want to hear.¹ Self-reports and physician evaluations have typically evinced higher rates of adherence than methods of measurement such as electronic monitoring and pharmacy refill records, which tend to be more accurate.^1,2

Measurement of blood drug levels may be a useful tool for assessing adherence. In a recent clinical trial (ClinicalTrials.gov identifier: NCT01509989) led by Nathalie Costedoat-Chalumeau of Hopital Cochin, Paris, France, nonadherence was evaluated in 305 patients with SLE with flares using drug levels (hydroxychloroquine <200 ng/mL or undetectable desethylchloroquine, its main metabolite) and self-administered questionnaires.⁷ Hydroxychloroquine, a high-efficacy, relatively nontoxic steroid-sparing agent used to prevent flare and prevent organ damage, is considered to be the cornerstone of treatment for patients SLE. Some experts have suggested that all patients with SLE should receive the drug. It is the most commonly prescribed antimalarial agent in SLE and one of the few licensed drugs for the disease.^2,6

Nonadherence rates were 18.4% as determined by blood levels, 23.4% as determined by questionnaire, and 31.5% overall, revealing a lack of overlap among measurements. Results of these 2 methods of measurement were correlated with physician evaluations of nonadherence. Questionnaires and blood drug measurements captured different forms of nonadherence: questionnaires revealed infrequent yet clinically significant missed doses, whereas drug levels revealed severe nonadherence (little to no intake of medication). One of 5 patients was found to be severely nonadherent, frequently without the physician’s knowledge.⁷ Based on these results and the imperative to avoid unnecessary treatment escalation with steroids, the investigators recommended routine measurement of drug levels and the use of questionnaires to assess nonadherence in people with SLE receiving hydroxychloroquine.⁷

“An objective tool like therapeutic drug monitoring may alert the clinician that there is something happening with the patient that [she or he] was not aware of,” commented Dr Heiman, who was not involved in the hydroxychloroquine monitoring trial. “This can lead to a more in-depth discussion of the patient’s motivations and barriers to taking his or her medications. Based on our findings, I suspect that depressive symptoms will be playing a role in many of these situations. As with any tool that tells you about a patient’s behavior, and doesn’t rely on the patient’s own self-report, a clinician must be sure to address the issue in a caring and supportive manner, rather than an accusatory one, in order to maintain a positive patient-clinician relationship and pave the way towards better outcomes.”

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References

1. 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(3):329-340.
2. 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 (Hoboken). 2015;67(12):1712-1721.
3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487-497.
4. Feldman CH, Collins J, Zhang Z, et al. Dynamic patterns and predictors of hydroxychloroquine nonadherence among Medicaid beneficiaries with systemic lupus erythematosus [published online January 8, 2018]. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2018.01.002
5. Heiman E, Lim SS, Bao G, Drenkard C. Depressive symptoms are associated with low treatment adherence in African American individuals with systemic lupus erythematosus. J Clin Rheumatol. 2018;24:368-374.
6. Gordon C, Amissah-Arthur M-B, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford). 2018;57(1):e1-e45.
7. Costedoat-Chalumeau N, Houssiau F, Izmirly P, et al. A prospective international study on adherence to treatment in 305 patients with flaring SLE: assessment by drug levels and self-administered questionnaires. Clin Pharmacol Ther. 2018;103(6):1074-1082.