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Protective effects of antimalarials in Chinese patients with systemic lupus erythematosus
  1. Fan Wang1,
  2. Wei Zhang2,3,
  3. Shiying Wang1,
  4. Wenyou Pan4,
  5. Lin Liu5,
  6. Min Wu6,
  7. Fuwan Ding7,
  8. Huaixia Hu8,
  9. Xiang Ding9,
  10. Hua Wei10,
  11. Yaohong Zou11,
  12. Xian Qian12,
  13. Meimei Wang13,
  14. Jian Wu14,
  15. Juan Tao15,
  16. Jun Tan16,
  17. Zhanyun Da17,
  18. Miaojia Zhang18,
  19. Jing Li19,
  20. Xuebing Feng1,
  21. Lingyun Sun1
  1. 1 Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
  2. 2 Department of Rheumatology and Immunology, The Affiliated Drum Tower Clinical Medical School, Nanjing Medical University, Nanjing, China
  3. 3 Department of Rheumatology, Nanjing Medical University Affiliated Jiangning Hospital, Nanjing, China
  4. 4 Department of Rheumatology, Huaian First People’s Hospital, Huaian, China
  5. 5 Department of Rheumatology, Xuzhou Central Hospital, Xuzhou, China
  6. 6 Department of Rheumatology, The Third Affiliated Hospital of Soochow University, Changzhou, China
  7. 7 Department of Endocrinology, Yancheng Third People’s Hospital, Yancheng, China
  8. 8 Department of Rheumatology, Lianyungang Second People’s Hospital, Lianyungang, China
  9. 9 Department of Rheumatology, Lianyungang First People’s Hospital, Lianyungang, China
  10. 10 Department of Rheumatology, Northern Jiangsu People’s Hospital, Yangzhou, China
  11. 11 Department of Rheumatology, Wuxi People’s Hospital, Wuxi, China
  12. 12 Department of Rheumatology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China
  13. 13 Department of Rheumatology, Southeast University Zhongda Hospital, Nanjing, China
  14. 14 Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, China
  15. 15 Department of Rheumatology, Wuxi TCM Hospital, Wuxi, China
  16. 16 Department of Rheumatology, Zhenjiang First People’s Hospital, Zhenjiang, China
  17. 17 Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China
  18. 18 Department of Rheumatology, Jiangsu Province Hospital, Nanjing, China
  19. 19 Department of Rheumatology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
  1. Correspondence to Professor Lingyun Sun; lingyunsun{at}nju.edu.cn and Dr Xuebing Feng, Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China; fengxuebing{at}hotmail.com

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We read with great interest the article by Müller-Calleja et al 1 in which a novel mechanism of hydroxychloroquine (HCQ) was discovered, which might explain well-established anti-inflammatory effects of antimalarials.2–4 HCQ and chloroquine (CQ), both known as antimalarial drugs, have become fundamental therapeutic elements in systemic lupus erythematosus (SLE) in these decades. However, their specific benefits on organ involvement and long-term outcome remain to be elucidated.

To examine the role of antimalarials in different clinical aspects of Chinese patients with SLE, we retrieved the medical records of 1372 patients with SLE who experienced their first hospitalisation at 26 centres across Jiangsu, an eastern province of China, between January 1999 and December 2009 from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group.5 Demographics of the enrolled patients are summarised in table 1. All the patients were followed up in 2015 to check for their survival status. Based on Kaplan-Meier survival analysis, the survival proportions for antimalarial users were 92.6%, 90.3% and 87.8% at 5, 10 and 16 years, significantly higher than that of non-users (83.1%, 78.9% and 76.0%, p=0.000) (figure 1A), which was consistent with previous reports in Latin American, African-American and Caucasian patients with SLE.6–8 There was no difference in survival proportions between HCQ users and CQ users.

Table 1

Baseline characteristics of the patients with systemic lupus erythematosus by usage of antimalarials

Figure 1

(A) Survival curves of patients with systemic lupus erythematosus (SLE) divided by whether using antimalarial drugs. (B) Examinations of HRs of SLE patients’ characters in using antimalarials. HRs are shown with 95% CI. (C) Comparisons of survival according to SLE patients’ organ involvements and antimalarial usage. SDI, Systemic Lupus International Collaborating and Clinics /American College of Rheumatology Damage Index ; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index.

In previous studies, the protective role of antimalarials was mainly concentrated on lupus nephritis.9 To further clarify this question, we performed univariate Cox proportional hazards regression analysis according to antimalarial exposure status on various clinical features. As shown in figure 1B, antimalarial drugs could exert their protective roles on a wide range of aspects, including but not limited to female gender, longer disease duration, a variety of organ involvement, hypocomplementemia and administration of glucocorticoids as well as cyclophosphamide. Besides renal involvement, patients with cardiopulmonary, gastrointestinal or haematological impairments also benefited from antimalarial treatment (all p<0.0001 by Kaplan-Meier survival analysis, figure 1C). Since antimalarials could interference with the assembly of endosomal NADPH oxidase to inhibit the overactivity of immune system,1 users were expected to have better outcomes than non-users when they were accompanied with vital organ involvements.

The effect of antimalarials on alleviating organ damage may also be related to lipid lowering,2 glycaemic controlling3 and thrombosis prevention.4 In this cohort, 376 patients had the record of second hospitalisation before 2015, of which 165 received antimalarial treatment. Blood level of total cholesterol was lower in antimalarial treating group than the non-treated group (4.47±1.25 mmol/L vs 5.04±2.17 mmol/L, p<0.05), and there was no difference between the two groups in the first hospitalisation. Other metabolic data, such as systolic and diastolic blood pressure, fasting blood sugar, triglyceride and uric acid, were similar between the two groups in two times of hospitalisation. Although percentages of leucopenia, anaemia and thrombocytopenia were similar between antimalarial users and non-users during the first hospitalisation, non-users were more likely to be anaemia on their second inpatients visits (46.5% vs 58.2%, p<0.05).

In conclusion, our data show that the use of antimalarials could improve long-term outcome of Chinese patients with SLE. These drugs possess protective effects on a wide range of clinical aspects. Patients with vital organ involvements, especially cardiopulmonary, gastrointestinal, renal or haematological impairments, may gain more benefits from antimalarial treatments.

Acknowledgments

The authors thank all those members of Jiangsu Lupus Collaborative Group who followed up the patients and helped data collection. They acknowledge the Cinkate Corp for helping build and manage their lupus database.

References

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Footnotes

  • FW and WZ contributed equally.

  • Contributors FW and WZ collected data, analysed results and FW wrote the manuscript. SW, WP, LL, MW, FD, HH, XD, HW, YZ, XQ, MW, JW, JTao, JTan, ZD, MZ and JL acquired clinical data. LS and XF designed the study. XF edited the manuscript. LS supervised the project. All authors made substantial intellectual contributions to conception of the work, the interpretation of data and approval of the final manuscript.

  • Funding This study was funded by National Natural Science Foundation of China (grant no: 81302559, 81373198), Nanjing Medical Science and Technique Development Foundation (grant no: QRX17122), Jiangsu Provincial Special Program of Medical Science (grant no: BE2015602).

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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