Abstract
INTRODUCTION: In the type 1 and 2 SLE model, inflammation mediates type 1 manifestations, but its role in type 2 manifestations (eg, fatigue, myalgias, mood disturbance, cognitive dysfunction) is less clear. Therapeutic hydroxychloroquine (HCQ) levels reduce type 1 activity, but their relationship with type 2 activity is unknown. Exploring this relationship may illuminate type 2 SLE pathophysiology. METHODS: We measured whole blood HCQ levels using liquid chromatography-mass spectrometry, categorising them as underexposure (<200 ng/mL), subtherapeutic (200 to <750 ng/mL) or therapeutic (≥750 ng/mL). We measured type 1 SLE activity using the type 1 Physician Global Assessment (PGA) and Systemic Lupus Erythematosus Disease Activity Index and type 2 SLE activity using the type 2 PGA and patient-reported polysymptomatic distress scores. Patients were categorised into minimal (low type 1 and type 2), type 1 (high type 1 and low type 2), type 2 (low type 1 and high type 2) and mixed activity (high type 1 and type 2) groups. We analysed relationships between HCQ levels and type 1 and type 2 SLE activities. RESULTS: Among 154 patients (median age 43, 90% women, 63% Black race, 7% Hispanic ethnicity) across 297 visits, HCQ levels were underexposed at 41 (14%) visits, subtherapeutic at 76 (26%) and therapeutic at 180 (61%) visits. Patients had minimal activity at 102 visits (34%), type 1 activity at 33 (11%), type 2 activity at 85 (29%) and mixed activity at 77 (26%) visits.Underexposed HCQ levels were independently associated with higher type 1 (OR 2.33, 95% CI 1.23 to 4.44) and type 2 activities (OR 1.80, 95% CI 1.07 to 3.04). Mixed activity most strongly associated with Underexposed HCQ levels (OR 3.4-10.3, p<0.05). CONCLUSIONS: Low HCQ levels are associated with increased type 1 and type 2 SLE activities, particularly for the mixed activity group, suggesting that immunologic activity may contribute to type 2 symptoms in some patients.