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