Low hydroxychloroquine levels may signal nonadherence in SLE
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Low hydroxychloroquine levels in the blood among patients with systemic lupus erythematosus are associated with reported nonadherence, according to a meta-analysis published in Arthritis Care & Research.
“Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus to reduce disease activity and improve damage-free-survival,” Shivani Garg, MD, MS, of the University of Wisconsin School of Medicine and Public Health, told Healio Rheumatology. “Yet, up to 83% of lupus patients are nonadherent to HCQ. Conversely, some patients have refractory lupus despite taking HCQ regularly and require treatment escalation. Diagnosing nonadherence is therefore a critical step in the care of patients who have uncontrolled lupus.”
“Although studies recommend performing hydroxychloroquine blood levels to differentiate severe nonadherence from refractory disease, there is insufficient information on the overall clinical impact of incorporating routine testing of hydroxychloroquine blood levels,” she added.
To evaluate the relationship between hydroxychloroquine levels, nonadherence and SLE disease activity index (SLEDAI) scores among patients with SLE, Garg and colleagues conducted a meta-analysis following a systematic review of relevant publications. The literature search was performed using Medline, Embase, CINHL and Web of Science databases in August 2018 and June 2019. The researchers limited themselves to articles published between Jan. 1, 1997, and June 1, 2019.
Among the 604 unique articles included in the initial screening, the researchers selected 17 studies for the final analysis. These included 13 observational studies and four interventional studies. All studies chosen for data extraction assessed adherence or SLEDAI among adults with SLE. In addition, the researchers used forest plots to compare pooled estimates of correlations between hydroxychloroquine levels, nonadherence reported by patients or physicians, and SLEDAI scores.
According to the researchers, patients with low hydroxychloroquine levels demonstrated three times higher odds of reported nonadherence (OR = 2.95; 95% CI, 1.63-5.35). In an a priori analysis, the mean SLEDAI score was 3.14 points higher among patients with below-threshold hydroxychloroquine levels (delta = 3.14; 95% CI –0.05 to 6.23; P = .053), and 1.4 points higher among those with hydroxychloroquine levels below 500 ng/mL (delta = 1.42; 95% CI, 0.07-2.76; P = .039).
In 1,223 patients, those with hydroxychloroquine levels of 750 ng/mL or greater demonstrated a 58% lower risk for active disease, with a SLEDAI score that was 3.2 points lower.
“Our metanalysis found good association between reported nonadherence and low HCQ levels,” Garg said. “Therefore, we recommend using objective measurement of HCQ blood levels to assess nonadherence during routine clinic visits or self-report questionnaires when HCQ levels are not feasible.”
“Our systematic review consistently reported a strong correlation with flares in patients with low hydroxychloroquine levels,” she added. “Future studies are needed to confirm clinically relevant thresholds to identify nonadherence and risk for active SLE.” – by Jason Laday
Disclosure: The researchers report no relevant financial disclosures.
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