Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study.

IF 3.7 2区医学 Q1 RHEUMATOLOGY

Lupus Science & Medicine Pub Date : 2025-06-30 DOI:10.1136/lupus-2025-001531

Kai Sun, Roberta Vezza Alexander, Amanda M Eudy, Megan E B Clowse, Stephen J Balevic, Tyler O'Malley, Rebecca E Sadun, Mithu Maheswaranathan, Jayanth Doss, Lisa G Criscione-Schreiber, Jennifer L Rogers

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引用次数: 0

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.

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羟基氯喹血药水平与狼疮活动性的关系通过1型和2型狼疮模型：一项横断面研究。

在1型和2型SLE模型中，炎症介导1型表现，但其在2型表现（如疲劳、肌痛、情绪障碍、认知功能障碍）中的作用尚不清楚。治疗性羟氯喹（HCQ）水平可降低1型活性，但其与2型活性的关系尚不清楚。探索这种关系可能有助于阐明2型SLE的病理生理。方法：我们使用液相色谱-质谱法测量全血HCQ水平，将其分为暴露不足(最低（低1型和2型）、1型（高1型和低2型）、2型（低1型和高2型）和混合活性（高1型和2型）组。我们分析了HCQ水平与1型和2型SLE活动之间的关系。结果：154例患者（中位年龄43岁，90%为女性，63%为黑人，7%为西班牙裔）在297次就诊中，HCQ水平暴露不足的有41例（14%），亚治疗的有76例（26%），治疗的有180例（61%）。患者在102次就诊时活动最少（34%），1型活动33次（11%），2型活动85次（29%），混合活动77次（26%）。暴露不足的HCQ水平与较高的1型（OR 2.33, 95% CI 1.23至4.44）和2型活性（OR 1.80, 95% CI 1.07至3.04）独立相关。结论：低HCQ水平与1型和2型SLE活动增加相关，特别是混合活动组，提示免疫活动可能导致某些患者出现2型症状。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lupus Science & Medicine RHEUMATOLOGY-

CiteScore

5.30

自引率

7.70%

发文量

审稿时长

15 weeks

期刊介绍： Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.