medwireNews: The authors of a systematic review and meta-analysis have identified significant associations between blood hydroxychloroquine levels and adherence to the drug among patients with systemic lupus erythematosus (SLE).
“Despite the pivotal role that hydroxychloroquine plays in treating SLE, less than 50% of patients take [the agent] as prescribed,” whereas “some patients have refractory lupus despite taking [hydroxychloroquine] regularly and require treatment escalation,” say Shivani Garg (University of Wisconsin, Madison, USA) and colleagues.
“Diagnosing nonadherence is therefore a critical step in the care of patients who have uncontrolled lupus,” they add.
The analysis included a total of 17 studies – 13 observational and four interventional – that measured hydroxychloroquine levels and either drug adherence or disease activity in patients with SLE.
As reported in Arthritis Care & Research, patients with low blood hydroxychloroquine levels were approximately three times more likely than those with higher levels to have self- or physician-reported nonadherence to the drug, with a pooled odds ratio of 2.95 based on four studies.
Garg et al note that the threshold hydroxychloroquine level for defining nonadherence was “variable in different studies,” and there was a moderate level of publication bias.
The researchers also found that hydroxychloroquine levels could be indicative of disease activity. When the findings from 10 studies measuring disease activity were pooled, the average SLEDAI score was 3.14 points higher in patients with hydroxychloroquine levels below the therapeutic threshold relative to those with higher levels. The between-group difference did not reach statistical significance, but significant results were observed when individual patient data were analyzed.
Specifically, each stepwise 250 ng/mL increase in hydroxychloroquine levels from below 250 to 749 ng/mL was associated with a significant 1.7-point decrease in SLEDAI score, while an increase in drug levels from below 250 to 750 ng/mL or greater was associated with a significant 3.2-point decrease.
Moreover, in a logistic regression analysis, patients with hydroxychloroquine levels of 750 ng/mL and above had a 58% lower risk for active SLE than those with lower levels, which lends support to “the use of levels <750 ng/ml as a clinical threshold to predict active lupus and lupus disease flares,” says the team.
“Future prospective clinical trials could confirm ≥750 ng/ml as a clinically relevant threshold for interpreting and targeting [hydroxychloroquine] levels,” recommend Garg et al.
They conclude that routine clinic visits for SLE should include “objective measurement of [hydroxychloroquine] blood levels to assess nonadherence,” and advocate self-reported adherence questionnaires for when blood measurements are not feasible.
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