Predictors may help to spot risk for hydroxychloroquine nonadherence

Varying degrees of nonadherence to hydroxychloroquine (HCQ) treatment characterize the great majority of patients with systemic lupus erythematosus on Medicaid who are newly prescribed the antimalarial, an administrative claims database study has revealed.

Investigators from Brigham and Women’s Hospital, Boston, used prescription refill data to assess nonadherence, hoping to gain greater insight into predictors of nonadherence to HCQ than past studies of nonadherence to the drug, which have been limited by their small and cross-sectional nature and the fact that they often relied on self-reported measures of adherence that were unable to capture the dynamic nature of adherence behavior over time.

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In the current study, Candace H. Feldman, MD, ScD, and her coinvestigators used Medicaid data from 28 U.S. states to identify 10,406 adult HCQ initiators with SLE during 2001-2010. Patients included in the study were required to have more than 365 days of continuous follow-up documented.

The researchers described four distinctive monthly patterns of behavior during the first year of use, in which they defined nonadherence as less than 80% of days covered per month by a HCQ prescription. Group 1 comprised 36% who were “persistent nonadherers” who had very few HCQ refills after the initial dispensing.

Almost half of the cohort (47%) formed two dynamic patterns of partial adherence (groups 2 and 3). The trajectories for these groups were similar until month 5, when they diverged: group 3 improved slightly and then reached a plateau, whereas group 2 became nearly completely nonadherent for the remainder of follow-up. At this 5-month point of divergence, belonging to group 2 was more likely among patients with younger age and antidepressant use. Also, patients in group 3 had more hospitalizations beginning at 4 months and longer hospitalizations at 5 months.

For these two “undecided” groups, 5 months may be a “critical juncture” for physicians to intervene, the authors said.

“Five months might also be the point at which patients feel that they have adequately trialed the medication, and if there is no symptomatic improvement, they discontinue. With the growing body of literature suggesting long-term preventive effects from HCQ, increased provider and patient education at this juncture may be beneficial,” they wrote.

Group 4 had persistent adherence and constituted 17% of the cohort, although this group also experienced a decline in adherence at 9 months.

The mean age of group 4 was about 40 years, which was significantly older than 37 years in groups 1-3. Blacks comprised the highest percentage of patients in groups 1-3 (43%-45%), whereas whites at 40% were the highest proportion in group 4. Individuals in group 4 also had slightly higher average income than did group 1 (mean $46,000 vs. $44,000). The index for SLE risk adjustment was highest for group 4 patients (1.3 vs. 0.9-1.1 for other groups), indicating they may have had more SLE-related comorbidities. Group 4 patients also had a greater average number of medications dispensed and a higher mean daily prednisone-equivalent dose.

Patients aged 18-50 or with black race or Hispanic ethnicity were significantly more likely to be in one of the nonadherent trajectory groups (1, 2, and 3), whereas Asians were less likely to be in group 1 than in group 4, compared with whites.

Diabetes made patients more likely to belong to group 1 than group 4, whereas each unit increase in the SLE risk-adjustment index increased the odds of belonging to group 1 vs. 4. Antidepressant use was associated with greater likelihood of belong to groups 1 or 2 vs. group 4.

Addressing potentially modifiable factors such as ensuring sustained access to health care, particularly for patients with severe disease, might go some way to improving adherence, suggested the researchers, who also noted that increased counseling and support at the time of the first HCQ prescription and throughout the first year of use are also needed in order to “promote more sustained patterns of adherence for all patients.”

The study was funded by a Rheumatology Research Foundation Investigator Award and individual grant awards from the National Institutes of Health. No relevant financial disclosures were declared by the authors.

SOURCE: Feldman C et al. Semin Arthritis Rheum. 2018 Jan 8. doi: 10.1016/j.semarthrit.2018.01.002