Introduction:
Hydroxychloroquine (HCQ) is a cornerstone therapy in systemic lupus erythematosus (SLE), yet treatment benefit depends on adequate and sustained drug exposure. Whole-blood HCQ level measurement may provide an objective approach to detect subtherapeutic exposure and could potentially support individualised clinical decision-making. The study aims to determine the proportion of SLE patients reaching a literature-defined therapeutic HCQ range and to identify independent pharmacokinetic determinants of measured HCQ concentrations in routine care.

Material and Methods:
In a cross-sectional observational study, consecutive adult SLE outpatients were recruited at Semmelweis University between November 1 and December 17, 2025. Whole-blood HCQ levels were quantified using a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) method. Of 35 enrolled patients, 32 were included in the final analysis. Target attainment was defined as 750–1,200 ng/ml. A one-sided exact binomial test evaluated whether ≥ 50% of patients were within range. Multivariable linear regression modelled HCQ levels using weight-adjusted daily dose, estimated glomerular fil tration rate (eGFR), and time from last intake to blood draw.

Results:
Only 6/32 patients (18.8%) achieved the 750–1,200 ng/ml therapeutic range; this proportion was significantly below 50% (p = 0.00027; exact 95% CI: 0.000–0.337). In the regression model (F = 8.98, p = 0.001; adjusted R² = 0.51), higher eGFR was independently associated with lower HCQ levels (β = −13.49; 95% CI: from −23.58 to −3.40; p = 0.011), and longer time since last intake was also associated with lower levels (β = −14.79 per hour; 95% CI: from −26.80 to −2.78; p = 0.018). Weight-adjusted dose showed a positive but non-significant association (β = 64.64; p = 0.237).

Discussion:
These preliminary findings suggest that subtherapeutic HCQ exposure is common in routine care despite ongoing treatment. The results highlight the limitations of dose-based prescribing, while emphasising the clinical relevance of pharmacokinetic factors such as renal function.

Conclusions:
In this preliminary real-world cohort, most SLE patients did not achieve the predefined therapeutic HCQ exposure range despite ongoing treatment. These findings suggest that dose-based prescribing alone may be insufficient to ensure adequate drug exposure. Whole-blood HCQ monitoring could help identify patients with subtherapeutic levels and potentially support a more individualised therapeutic approach by distinguishing nonadherence from pharmacokinetic variability.