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Observational Study
. 2023 Sep 1:14:1227403.
doi: 10.3389/fimmu.2023.1227403. eCollection 2023.

Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry

Chiharu Hidekawa  1 , Ryusuke Yoshimi  1   2 , Yusuke Saigusa  3 , Jun Tamura  3 , Noriko Kojitani  1 , Naoki Suzuki  1 , Natsuki Sakurai  1 , Yuji Yoshioka  1 , Yumiko Sugiyama-Kawahara  1 , Yosuke Kunishita  1 , Daiga Kishimoto  4 , Kana Higashitani  1 , Yuichiro Sato  1 , Takaaki Komiya  1 , Hideto Nagai  1 , Naoki Hamada  1 , Ayaka Maeda  1 , Naomi Tsuchida  1 , Lisa Hirahara  1 , Yutaro Soejima  1 , Kaoru Takase-Minegishi  1 , Yohei Kirino  1 , Nobuyuki Yajima  5 , Ken-Ei Sada  6 , Yoshia Miyawaki  7 , Kunihiro Ichinose  8 , Shigeru Ohno  4 , Hiroshi Kajiyama  9 , Shuzo Sato  10 , Yasuhiro Shimojima  11 , Michio Fujiwara  12 , Hideaki Nakajima  1
Affiliations
Observational Study

Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry

Chiharu Hidekawa et al. Front Immunol. .

Abstract

Objectives: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients.

Methods: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection.

Results: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p<0.001), immunosuppressants (OR 1.561 [1.025-2.380], p=0.038), and baseline age (OR 1.043 [1.027-1.060], p<0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p=0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group (p<0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p=0.005) and HCQ (HR 0.322 [0.142-0.728], p=0.006) were significantly related to incidence.

Conclusion: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates.

Keywords: Asian; hydroxychloroquine; infection; multicenter registry; systemic lupus erythematosus (SLE).

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Conflict of interest statement

KS received a speaker’s fee from GlaxoSmithKline PLC and research grants from Pfizer Inc. YKi received a speaker’s fee from Amgen and Novartis and research funding from Nippon Shinyaku. RY received a speaker’s fee from GlaxoSmithKline PLC, AstraZeneca PLC, and Sanofi S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient selection flow chart. Of the 1,543 patients enrolled in the LUNA registry from 2016 to 2021, data from 925 patients who were followed up for > 1 year were included. A total of 193 patients were excluded because their HCQ adherence status during the follow-up was unknown. Of the remaining 732 patients, 296 who had been taking HCQ for more than one year were classified into the HCQ group and 436 who had never taken HCQ were classified into the non-HCQ group. HCQ, hydroxychloroquine.
Figure 2
Figure 2
Kaplan–Meier curve for the occurrence of the first severe infection. Survival time curves for the HCQ and non-HCQ groups for the first severe infection that occurred during the follow-up period. The non-HCQ group had a significantly higher incidence of infection compared to that of the HCQ group. The hazard values were derived based on the univariate analysis. HCQ, hydroxychloroquine.
See this image and copyright information in PMC

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