Current guidelines for treating systemic lupus erythematosus (SLE) support weight-based dosing for hydroxychloroquine (HCQ), but the guidelines lack specific recommendations on adjusting the dose based on kidney function or other clinical factors that can introduce individual variability in drug metabolism and clearance.

In a study published on April 15, 2026, in Arthritis Care and Research, researchers found that kidney function and other factors can contribute to too low or too high HCQ levels, and monitoring the levels can improve SLE control and lead to optimal HCQ use.

Doses May Be Arbitrarily Reduced

“Without clear guidance on adjusting HCQ doses in patients with chronic kidney disease (CKD) or chronic transaminitis, doses are either not adjusted or arbitrarily reduced, which could potentially accelerate toxicity risk or increase the risk of SLE flares,” the authors wrote. “Moreover, the ‘one-size-fits-all’ dosing of HCQ exacerbates patients’ worry about irreversible eye toxicity [retinopathy] resulting in early discontinuation of the medicine or nonadherence risking lupus flares and hospitalizations.”

Researchers used longitudinal data from a prospective SLE cohort of 247 patients (962 patient visits) to predict HCQ blood levels for weight-based HCQ dosing stratified by CKD stages, chronic transaminitis categories, and gastric disease. Then they measured associations between target therapeutic HCQ blood levels (750-1150 ng/mL) and SLE response over time, accounting for individual patient factors.

Risk Extends to Stage 2B CKD

The study was able to show that it’s not just patients who have stage 3 CKD and above who are at higher risk of having the high HCQ levels associated with higher risk for retinopathy but also patients in stage 2B with an estimated glomerular filtration rate of 75 to > 60 mL/min/1.73 m², senior author Shivani Garg, MD, PhD, who was the medical director of the lupus and lupus nephritis clinics at the University of Wisconsin-Madison, at the time of the study but is now an associate professor in the Section of Rheumatology at the Yale School of Medicine, New Haven, Connecticut, where she serves as director of the Yale Lupus Clinical Research Program and co-director of the Yale Lupus Program.

Previous studies have not had the longitudinal data demonstrating the extent to which kidney impairment alters HCQ levels, information important to determine safe and effective HCQ dosing beyond current dosing based only on body weight, the authors pointed out.

Additionally, the longitudinal cohort study indicates that having very low (< 200 ng/mL) and subtherapeutic levels (200 to < 750 ng/mL) predicted 6.7-fold and 2.6-fold higher odds for active SLE vs therapeutic levels over time.

Dramatic Differences in Odds of Active SLE

Other findings showed that 100-ng/mL increases in HCQ levels at individual patient visits predicted 33% and 22% lower odds of active SLE and flares, respectively. And when patients maintained target therapeutic HCQ levels (≥ 750 ng/mL) through all visits, they had 83% lower odds of active SLE over time compared with patients who consistently had subtherapeutic levels.

Reasons for resistance in routine monitoring may come from several factors, including that it is a newer concept in the US, while it has been well established in Europe for two decades, Garg said, noting that the idea is gaining traction with more data.

Cost may also be slowing adoption of the monitoring, she said. “There has been a concern that the cost would be $200-$250,” she said, each time the blood level is monitored, though she said insurance typically covers the cost, according to their data.

“These data answer how the blood levels can contribute to improving outcomes, and now the next step is how clinicians can use it in their clinics. We are now gathering feedback,” she said.

Number of Blood Tests Grows at Michigan Medicine

Researchers at Michigan Medicine in Ann Arbor, Michigan, are also gathering feedback as they study the merits of monitoring HCQ levels in treating patients with SLE. They stated in an abstract presented at the American College of Rheumatology (ACR) 2025 Annual Meeting that their goal was to increase HCQ blood level testing at their institution from 4% to 25% within 6 months.

“We strongly believe this will help the disease control of our patients,” Zeinab Saleh, MD, clinical assistant professor of internal medicine at Michigan Medical School and lead author of that abstract, said in an interview.

They’re currently at 15%, she said, and “we definitely need more awareness of the importance of this blood test.” She also said they have not found problems with insurance coverage of the test in their health system and found it reassuring in this current study that cost did not prove limiting.

The strength of the current study, Saleh said, is that “most patients had the same dose of hydroxychloroquine according to their weight, but it showed they can metabolize their medication differently and have different blood levels and that might differ over time.”

Most previous studies on the topic have been cross sectional and looked at one point in time, she pointed out. “This one followed them for 3-plus years,” she said.

The research was supported by the Lupus Foundation of America, Wisconsin chapter.

The study authors and Saleh reported having no relevant financial disclosures.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape.