Pos1126 therapeutic range of hydroxychloroquine blood levels can reduce odds of high lupus disease activity

Background Hydroxychloroquine (HCQ) is the cornerstone of systemic lupus erythematous (SLE or lupus) treatment, yet, the optimal dosing of HCQ in SLE is unknown. Reducing HCQ dose to 5 mg/kg to limit toxicity, as suggested by the American Academy of Ophthalmologists (AAO),(1) also predicts increased flares.(2) One study showed six-fold higher risk of severe SLE flares in patients receiving AAO recommended HCQ dosing.(2) Therefore, establishing effective therapeutic ranges of HCQ blood levels may provide an opportunity to individualize HCQ dosing to maximize efficacy and limit toxicity. Objectives The objective of this study was to examine the association of HCQ blood levels with high lupus disease activity (HDA) in a prospective SLE cohort. Methods This cross-sectional study measured HCQ blood levels in unique SLE visits using liquid chromatography-tandem mass spectrometry. HCQ blood levels and SLE disease activity index (SLEDAI) scores were measured on the day of the visit for each patient. High lupus disease activity (HDA) was defined as SLEDAI scores of ≥6.(3) To identify significant HCQ blood levels that determined lower odds of HDA, we examined associations between HDA and every 50-100 ng/ml increase in HCQ blood levels starting at 100 ng/ml through 1500 ng/ml. Other factors that can affect HCQ levels, such as patient-reported adherence, kidney function, and HCQ dose and timing, were included in multivariable models. Results Among 143 SLE patients in whom HCQ blood levels were measured, 92% were women and 32% were of non-White race or Hispanic ethnicity. HDA was noted in 18% of patients. We noted a 75% reduction in the odds of HDA first at HCQ blood levels of ≥750 ng/ml (Adjusted OR 0.25, 95% CIs 0.066-0.89, p-value = 0.035; Figure 1). This effect peaked with HCQ blood levels ≥1100 ng/ml with 93% lower odds of HDA at this level (Adjusted OR 0.07, 95% CIs 0.005-0.61, p-value = 0.038; Figure 1). Interestingly, levels of 1150 ng/ml or higher did not further reduce the odds of HDA (Figure 1). Additionally, we noted that female sex was associated with 88% lower odds of HDA (Table 1), while other factors including HCQ dose or timing were not associated with HDA (Table 1). Conclusion We report an effective therapeutic range of HCQ blood levels, 750-1100 ng/ml, that significantly correlated with reduced risk of high lupus disease activity (HDA) by 75-93% in patients with SLE. These findings could guide clinicians to individualize HCQ doses to achieve target blood levels within this range to maximize efficacy, while balancing safety. References [1]Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394. [2)] Jorge AM, Mancini C, Zhou B, et al. Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares. JAMA. 2022;328(14):1458–1460. [3]Arora, S., Isenberg, D.A. and Castrejon, I. (2020), Measures of Adult Systemic Lupus Erythematosus: Disease Activity and Damage. Arthritis Care Res, 72: 27-46. Acknowledgments. The UW SLE Cohort is supported by the DOM and ICTR at UW-Madison. Figure 1. Effective range of HCQ levels (shaded box) that reduces odds of high SLE disease activity. Significant adjusted odds ratio shown in bold. Table 1. Factors Associated with High SLE Disease Activity (SLEDAI ≥6), Multivariable Model Variables Adjusted Odds Ratio (95% CIs) p-value Age (per 10 years increase) 0.99 (1.03, 9.6) 0.89 Female 0.11 (0.013, 0.83 ) 0.03 Non-White race & Hispanic ethnicity 0.75 (0.23, 2.3) 0.61 Weight (per 5 kg increase) 0.97 (0.93-1.01) 0.13 CKD stage ≥2 1.077 (0.29, 3.9) 0.91 HCQ total dose 200 mg daily ref 300 mg/d 1.8 (0.29, 22) 0.43 400 mg daily 3.0 (0.49, 22) 0.25 AAO-Guideline based dose, ≤5 mg/kg/day 1.4 (0.2, 12) 0.73 HCQ blood levels ≥1100 ng/ml 0.07 (0.004, 0.45 ) 0.02 Patient-reported adherence ≥80% 0.57 (0.16, 2.1) 0.38 Social Determinants of Health, Present 3.2 (0.86, 12) 0.99 HCQ dose timing <4 hours ref 4-6 hours 3.3 (0.15, 153) 0.48 6-8 hours 2.03 (0.1, 81) 0.66 >8 hours 0.15 (0.08, 60) 0.80 Disclosure of Interests Shivani Garg: None declared, Betty Chewning: None declared, Shelby Gomez: None declared, Christie Bartels Grant/research support from: Received an independent learning grant from Pfizer for a different research project.