Determining Adherence to Therapeutic Regimens in Patients With Chronic Illness: Comment on the Article by Waimann et al


We read with great interest the recent article by Waimann et al ([1]). Their study led to 2 major conclusions: 1) only one-fifth of patients with rheumatoid arthritis had an overall adherence to disease-modifying antirheumatic drugs (DMARDs) of at least 80%, and 2) nonadherent patients had higher disease activity across a 2-year followup period. Poor adherence to treatment is indeed very common in patients with chronic diseases and may have major clinical consequences. The problem is that poor adherence to therapeutic regimens is also very difficult to determine.

The authors discussed several methods that can be used. We agree that patient self-reports and clinician assessments lead to an underestimation of nonadherence. We also agree that electronic monitoring devices are considered the gold standard for measuring compliance, provided they are used over a long period of time; however, they are not routinely applicable and, as observed by the authors, many patients may refuse to use them. At the same time, we strongly disagree with the statement of the authors that performing biologic assays (e.g., for serum drug concentration) is difficult to implement “because of their invasiveness, high cost, and the variability in results owing to individual pharmacokinetics.”

In the field of rheumatology and particularly for patients with systemic lupus erythematosus (SLE), hydroxychloroquine (HCQ) is a widely available and inexpensive treatment that has proven to have a high efficacy-to-toxicity ratio profile. Another advantage of HCQ is its long terminal elimination half-life that leads to small intraindividual variations in blood concentrations. Blood assays for HCQ concentrations are not invasive, because such assays can be performed simultaneously with other blood tests and require only a minimum of 1 milliliter of blood. This assay is not very expensive. In France, the cost is approximately 33荤 ($46.00) compared with 19荤 ($26.00) for anti-DNA testing.

Finally, even though we agree that the interindividual variability in results owing to individual pharmacokinetics may be important ([2, 3]), we have shown that undetectable or very low blood HCQ concentrations necessarily mean that the patient has not received HCQ for a long time (not that he or she has simply forgotten to take the most recent dose), whereas the “white-coat” compliance effect in a patient with poor long-term adherence would not increase the blood HCQ concentration to normal levels ([4]). Using an undetectable blood HCQ concentration as a measure of compliance, Ting et al observed that 29% of adolescents and young adults with SLE were nonadherent ([5]). Medication adherence as estimated using blood HCQ concentrations correlated with adherence rates as measured using pharmacy refill information ([5]).

Regular assays of HCQ levels in whole blood, especially in patients with active SLE despite treatment, are now routinely performed in France. An undetectable or unexpectedly low HCQ concentration should prompt a nonjudgmental discussion with the patient. In patients with disease flares, this result may prevent incorrect interpretation of poor adherence as a lack of response, leading to unnecessary or even dangerous escalation of therapy. To our knowledge, other centers have developed this assay, especially centers in the UK, Canada, Brazil, and the US. The results of an ongoing international study evaluating the extent of nonadherence in SLE patients ( NCT01509989) may underline the interest in this blood measurement.