Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study
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 wi...
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BMJ Publishing Group
2025-06-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/12/1/e001531.full |
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| author | Rebecca E Sadun Kai Sun Amanda M Eudy Megan E B Clowse Roberta Vezza Alexander Stephen J Balevic Lisa G Criscione-Schreiber Mithu Maheswaranathan Jennifer L Rogers Jayanth Doss Tyler O’Malley |
| author_facet | Rebecca E Sadun Kai Sun Amanda M Eudy Megan E B Clowse Roberta Vezza Alexander Stephen J Balevic Lisa G Criscione-Schreiber Mithu Maheswaranathan Jennifer L Rogers Jayanth Doss Tyler O’Malley |
| author_sort | Rebecca E Sadun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6d36275afa1748bbbfb63d91f5c1169e |
| institution | DOAJ |
| issn | 2053-8790 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMJ Publishing Group |
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| series | Lupus Science and Medicine |
| spelling | doaj-art-6d36275afa1748bbbfb63d91f5c1169e2025-08-20T02:39:39ZengBMJ Publishing GroupLupus Science and Medicine2053-87902025-06-0112110.1136/lupus-2025-001531Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional studyRebecca E Sadun0Kai Sun1Amanda M Eudy2Megan E B Clowse3Roberta Vezza Alexander4Stephen J Balevic5Lisa G Criscione-Schreiber6Mithu Maheswaranathan7Jennifer L Rogers8Jayanth Doss9Tyler O’Malley10Pediatrics, Duke University Medical Center, Durham, North Carolina, USADepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USADuke University School of Medicine, Durham, North Carolina, USAMedicine, Duke University, Durham, North Carolina, USAExagen Inc, Vista, California, USAPediatric Rheumatology, Duke University, Durham, North Carolina, USAMedicine, Duke University Medical Center, Durham, North Carolina, USADuke University School of Medicine, Durham, North Carolina, USADepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USADepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USAExagen Inc, Vista, California, USAIntroduction 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.https://lupus.bmj.com/content/12/1/e001531.full |
| spellingShingle | Rebecca E Sadun Kai Sun Amanda M Eudy Megan E B Clowse Roberta Vezza Alexander Stephen J Balevic Lisa G Criscione-Schreiber Mithu Maheswaranathan Jennifer L Rogers Jayanth Doss Tyler O’Malley Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study Lupus Science and Medicine |
| title | Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study |
| title_full | Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study |
| title_fullStr | Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study |
| title_full_unstemmed | Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study |
| title_short | Relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model: a cross-sectional study |
| title_sort | relationship between hydroxychloroquine blood levels and lupus activity through the lens of the type 1 and type 2 lupus model a cross sectional study |
| url | https://lupus.bmj.com/content/12/1/e001531.full |
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