2059: Association of Hydroxychloroquine with the Incidence of Infectious Disease in Systemic Lupus Erythematosus: Data from the LUNA Registry

Chiharu Hidekawa¹, Ryusuke Yoshimi², Yusuke Saigusa³, Jun Tamura³, Nobuyuki Yajima⁴, Naoki Suzuki⁵, Noriko Kojitani², Yuji Yoshioka⁵, Natsuki Sakurai⁵, Yumiko Sugiyama⁵, Yosuke Kunishita⁶, Daiga Kishimoto⁷, Kana Higashitani⁵, Yuichiro Sato⁵, Takaaki Komiya⁵, Hideto Nagai², Naoki Hamada⁵, Ayaka Maeda⁵, Naomi Tsuchida⁵, Lisa Hirahara², Yutaro Soejima⁵, Kaoru Takase-Minegishi², Yohei Kirino⁵, Ken-ei Sada⁸, Yoshia Miyawaki⁹, Kunihiro Ichinose¹⁰, Shigeru Ohno¹¹, Hiroshi Kajiyama¹², Shuzo Sato¹³, Yasuhiro Shimojima¹⁴, Michio Fujiwara¹⁵ and Hideaki Nakajima⁵, ¹Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama City, Kanagawa Prefecture, Japan, ²Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan, ³Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan, ⁴Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan, ⁵Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan, ⁶Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Kanagawa, Japan, ⁷Center for Rheumatic Diseases, Yokohama City University Medical Center, Kanazawa-ku Yokohamashi, Japan, ⁸Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Okayama, Japan, ⁹Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Yokohama, Japan, ¹⁰Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Yokohama, Japan, ¹¹Center for Rheumatic Disease, Yokohama City University Medical Center, Yokohama, Japan, ¹²Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Yokohama, Japan, ¹³Department of Rheumatology, Fukushima Medical University School of Medicine, Hikarigaoka, Japan, ¹⁴Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan, ¹⁵Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan

Background/Purpose: Infections are significant causes of mortality in patients with systemic lupus erythematosus (SLE), and their prevention is essential. Although some previous reports have shown the efficacy of hydroxychloroquine (HCQ) in preventing infection, there is no such evidence in the Japanese population. Here we investigated the effect of HCQ on reducing infections in SLE patients in Japan using data from the Lupus Registry of Nationwide Institutions (LUNA) registry.

Methods: Patients older than 20 years and who met the 1997 ACR revised classification criteria were enrolled in the LUNA registry. We defined "severe infections" as infections that required inpatient treatment, and collected data on the type of infection, treatment, disease activity, and clinical and serological variables. To analyze the protective effect of the HCQ on infections using a generalized estimating equation (GEE) logistic regression model as primary endpoint, we converted all follow-up periods to person-years at each observation point. We defined the HCQ group as the period when the patient was taking HCQ both points before and after each annual observation period and the non-HCQ group as when the patient was not taking HCQ at both points. To analyze the survival time by log-rank test and perform a multivariate analysis of the association between the HCQ and the time until the first severe infection within the observation period, we defined the HCQ group as the patients who took HCQ for at least two observation points, and the non-HCQ group as those who did not take HCQ during the follow-up period. We used multiple imputation for missing data.

Results: A total of 925 patients were included in the study (median age 45 (IQR 35-57) years; female 88.1 %; the observation period 1-5 years). At enrollment, 267 patients were prescribed HCQ, while 656 were not. The median dose of glucocorticoid was 5.5 (IQR 4.0-9.0) mg/day and systemic lupus erythematosus disease activity index (SLEDAI) was 4 (IQR 2-8). A total of 110 severe infections were reported, with pulmonary infections the most common (29.1 %), followed by urinary tract infections (27.3 %) and skin and soft tissue infections (15.5 %). To examine the effect of HCQ and other factors on severe infections, we extracted 1,990 person-years. GEE analysis showed that severe infection was positively associated with the glucocorticoid dose (odds ratio [OR] 1.96 [95% confidence interval 1.38-2.81], p = 2.0×10^-4), immunosuppressive drugs (OR 1.56 [1.03-2.38], p = 0.038), and the age at baseline (OR 1.04 [1,03-1.06], p = 1.5×10^-7). HCQ tended to reduce the incidence of severe infections, although the difference was not statistically significant (OR 0.59 [0,33-1.06], p = 0.077). Survival time analysis showed that the HCQ group (n = 296) had a lower incidence of severe infection than the non-HCQ group (n = 436) (p = 3.1×10^-4). Using a cox proportional hazards model, we found that age at baseline (hazard ratio [HR] 1.033 [1.014-1.052], p = 6.0×10^-4) and HCQ (HR 0.32 [0.142-0.723], p = 6.0×10^-3) were significantly associated with incidence rate.

Conclusion: This study demonstrated that HCQ could reduce the incidence of infection, which may improve the clinical course of SLE patients.
Figure Probability of first severe infection during follow up period. The patients were divided into two groups, HCQ and non-HCQ group. We conducted a survival time analysis of first severe infection during follow up period. The results showed that the HCQ group had a significantly lower incidence of infection.
Disclosures: C. Hidekawa, None; R. Yoshimi, None; Y. Saigusa, None; J. Tamura, None; N. Yajima, None; N. Suzuki, None; N. Kojitani, None; Y. Yoshioka, None; N. Sakurai, None; Y. Sugiyama, None; Y. Kunishita, None; D. Kishimoto, None; K. Higashitani, None; Y. Sato, None; T. Komiya, None; H. Nagai, None; N. Hamada, None; A. Maeda, None; N. Tsuchida, None; L. Hirahara, None; Y. Soejima, None; K. Takase-Minegishi, None; Y. Kirino, None; K. Sada, None; Y. Miyawaki, None; K. Ichinose, None; S. Ohno, None; H. Kajiyama, None; S. Sato, None; Y. Shimojima, None; M. Fujiwara, None; H. Nakajima, None.