Compliance and persistence with hydroxychloroquine in patients with systemic lupus erythematosus

Background/Purpose: Lifelong treatment with hydroxychloroquine (HCQ) is now recommended for all patients with systemic lupus erythematosus (SLE) irrespective of disease severity or other therapy mainly due to its efficacy in preventing flare, achieving remission and reducing the risk of damage accrual. However, there is lack of data regarding adherence of HCQ treatment in SLE patients. We investigated compliance and persistence with HCQ treatment in SLE patients in clinical practice and analyzed the risk factors for poor adherence.

Methods: We conducted a retrospective longitudinal study including 235 SLE patients undergoing HCQ treatment between 2002 and 2016 at a university rheumatology center in South Korea. Compliance was assessed using 1-year medication possession ratio (MPR) and non-compliance was defined as 1-year MPR <0.8. Persistence was determined as time from HCQ treatment initiation to discontinuation without interruption for longer than 56 days.  The reasons for HCQ discontinuation were categorized as poor health literacy, adverse events, pregnancy or unknown factors. Poor health literacy was indicated as the discontinuation of HCQ due to lack of knowledge about its significance in SLE management.

Results: Mean age and median baseline SLEDAI-2K of participants were 31.5 years and 8, respectively. Mean 1-year MPR and the frequency of non-compliance were 88.4% and 19.9%, respectively. During the study period, HCQ discontinuation occurred in 115 (48.9%) patients and 1-year, 2-year and 5-year persistence rates were 80, 67.6 and 46.3%, respectively. The most common reason of non-persistence with HCQ treatment was poor health literacy (73%) followed by adverse events (10.4%), unknown factors (10.4%) and pregnancy (6.1%). SLE patients with SLEDAI-2K score <6 showed significantly worse persistence with HCQ than those with SLEDAI-2K score >=6, while SLE patients with biopsy-proven lupus nephritis had better HCQ persistence than those without this feature (Fig. 1). SLEDAI-2K score <6 was a significant risk factor for non-compliance (OR=2.98, p=0.001) and non-persistence (HR=1.55, p=0.046) with HCQ after adjusting confounding factors. In addition, older age was significantly associated with better persistence with HCQ (HR=0.97, p=0.005) and biopsy-proven lupus nephritis had a trend with better HCQ retention (HR=0.66, p=0.076) in multivariable Cox regression model. But, neither HCQ dose nor concomitant immunosuppressive agents showed significant association with HCQ adherence.

Conclusion: Overall adherence with HCQ in SLE patients was suboptimal in real practice and SLEDAI-2K score <6 was a risk factor for poor HCQ treatment adherence. Our data suggest the need to improve adherence with HCQ treatment in SLE patients, especially for those with low disease activity.

.