The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus

Menglu Pan; Ruimin Jin; Yaqian Dai; Beibei Gao; Yue Liu; Xinchen Peng; Jinping Qiao; Zongwen Shuai

doi:10.1016/j.intimp.2023.111269

The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus

Int Immunopharmacol. 2024 Jan 5:126:111269. doi: 10.1016/j.intimp.2023.111269. Epub 2023 Nov 25.

Authors

Menglu Pan¹, Ruimin Jin¹, Yaqian Dai², Beibei Gao³, Yue Liu¹, Xinchen Peng¹, Jinping Qiao⁴, Zongwen Shuai⁵

Affiliations

¹ Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, China.
² Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, China.
³ Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, China.
⁴ Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, China. Electronic address: jpqiao@ahmu.edu.cn.
⁵ Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui Province 230032, China. Electronic address: shuaizongwen@ahmu.edu.cn.

PMID: 38006753
DOI: 10.1016/j.intimp.2023.111269

Abstract

Objective: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity.

Methods: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity.

Results: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively).

Conclusions: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.

Keywords: Disease activity; Glucocorticoid; Hydroxychloroquine; Metabolite; Systemic lupus erythematosus.

MeSH terms

Antirheumatic Agents* / therapeutic use
Glucocorticoids / therapeutic use
Humans
Hydroxychloroquine / therapeutic use
Lupus Erythematosus, Systemic*
Tandem Mass Spectrometry

Substances

Hydroxychloroquine
Antirheumatic Agents
Glucocorticoids