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Subtherapeutic hydroxychloroquine levels linked to lupus nephritis, disease progression in SLE

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A clear association between subtherapeutic hydroxychloroquine (HCQ) concentration and the development of new-onset lupus nephritis (LN), as well as significant links to disease activity and cumulative organ damage in patients with systemic lupus erythematosus (SLE), were found in a new study.

The study involved 338 patients with SLE who were evaluated annually for 5 consecutive years. Demographic data, clinical and laboratory findings, patient global assessment (PGA), adjusted mean SLE Disease Activity Index 2000 (AMS), and Systemic Lupus International Collaborating Clinics (SLICC) damage index were assessed. Patients were categorized into 2 groups based on their serum HCQ concentration at baseline: subtherapeutic (less than 500 ng/mL) and therapeutic (500 ng/mL or higher).

The impact of HCQ concentration on clinical outcomes was analyzed using a generalized estimating equation (GEE).

At baseline, 287 out of 338 patients (84.9%) fell into the subtherapeutic HCQ group. This group exhibited a higher incidence of newly developed lupus nephritis (LN) and had been prescribed higher mean and cumulative doses of prednisolone compared to the therapeutic group.

In the multivariable analyses based on GEE, the subtherapeutic HCQ group consistently displayed higher AMS scores, PGA scores, and SLICC damage index scores throughout the 5-year study period.

Specifically, the subtherapeutic HCQ group had a significantly higher AMS score, indicating greater disease activity. They also had a higher PGA score, reflecting a worse patient assessment of overall disease activity. In addition, the subtherapeutic group demonstrated a higher SLICC damage index score, indicating more cumulative organ damage.

Kang JH, Choi SE, Park DJ, et al. Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus. Rheumatology (Oxford). 2023;kead306. doi: 10.1093/rheumatology/kead306. Epub ahead of print. PMID: 37335866.