Stay within hydroxychloroquine ‘therapeutic threshold’ to reduce active lupus, flare risk
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SAN DIEGO — Patients with lupus who maintained hydroxychloroquine blood levels of 750 ng/ml to 1,200 ng/ml exhibited 71% to 90% lower risk for high lupus disease activity, according to data presented at ACR Convergence 2023.
“Hydroxychloroquine is a great medication for lupus management, as it prolongs disease-free and damage-free survival in lupus, yet the optimal dosing of hydroxychloroquine is still unclear,” Shivani Garg, MD, MS, director of the University of Wisconsin-Madison Lupus and Lupus Nephritis Clinics, told Healio. “While ophthalmology guidelines highlight that doses at or above 5 mg/kg per day are associated with two times higher eye toxicity risk, recent studies have shown that doses at or below 5 mg/kg per day are associated with six times higher risk of having lupus flares.
“Many studies have been done on monitoring hydroxychloroquine blood levels, looking for a therapeutic cutoff or threshold,” she added. “[However,] a therapeutic cutoff is difficult to use in a clinical setting because a cutoff is difficult to maintain over time and can have some daily variations or changes in patient level factors, so the levels could fluctuate during visits.”
To define an effective range of hydroxychloroquine blood levels, Garg and colleagues measured hydroxychloroquine blood levels from 158 patients with systemic lupus erythematosus using liquid chromatography-tandem mass spectrometry. Hydroxychloroquine blood levels and SLE disease activity index (SLEDAI) scores were measured on the day of the visit for each patient, with high lupus disease activity defined as a SLEDAI score of 6 or greater. The researchers conducted a nonparametric spline regression analysis to determine hydroxychloroquine blood level cutoffs tied to reduction in risk for high disease activity.
To establish an effective therapeutic range, Garg and colleagues examined associations between high disease activity and each 5 ng/ml to 100 ng/ml increase in hydroxychloroquine blood levels, beginning at 100 ng/ml through 1,500 ng/ml, using both univariable and multivariable logistic regression models. The researchers also included factors that impact hydroxychloroquine levels, including kidney function and hydroxychloroquine dose and timing, in their analysis.
The researchers observed that hydroxychloroquine blood levels in the range of 750 ng/ml to 1,200 ng/ml significantly reduced the odds of high disease activity, while blood levels less than 700 and more than 1,250 did not reduce the odds of high disease activity.
“From the 750 [level] cut point, we noted a significant decline until levels of 1,200 were achieved, and then, when we set the cut point at 1,200, we noted no further reduction in the odds of having active lupus, so we showed a saturation of effect at that point,” Garg said. “We were able to define that the effective range is between 750 to 1,200, which is very much consistent with some of the data by pioneers who have shown that levels around 1,000 are effective.”
The researchers noted that hydroxychloroquine levels of 750 ng/ml lowered the risk for high disease activity by 76% (OR = 0.24; P = .016), with a sustained decline in the odds of high disease activity observed through 1,000 ng/ml. They also reported that peak effects were observed at levels of 1,200 ng/ml, with a 90% reduction in the odds of high disease activity.
“We noted that patients who maintain levels within this range, compared to patients who had subtherapeutic levels of less than 750, had 71% lower odds of active lupus,” Garg said. “If we know what an effective range is, and which levels are subtherapeutic or supratherapeutic, we may be able to develop a workflow for using hydroxychloroquine blood level monitoring, which has been missing in clinical use.”
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Garg S, et al. Abstract 0785. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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