. 2025 Jul 22;11(3):e005558.

doi: 10.1136/rmdopen-2025-005558.

Safety of mycophenolate mofetil in systemic lupus erythematosus maintenance therapy: insights from the LUNA registry in a nationwide prospective cohort study

Naoki Matsuoka¹, Nobuyuki Yajima^{2

3}, Eisuke Inoue⁴, Shuzo Sato⁵, Shotaro Ogawa⁵, Yuya Sumichika⁵, Kenji Saito⁶, Shuhei Yoshida⁵, Haruki Matsumoto⁵, Jumpei Temmoku⁵, Yuya Fujita⁵, Tomoyuki Asano⁵, Jumpei Fukita², Ken-Ei Sada^{7

8}, Kunihiro Ichinose⁹, Ryusuke Yoshimi^{10

11}, Shigeru Ohno¹², Hiroshi Kajiyama¹³, Yasuhiro Shimojima¹⁴, Michio Fujiwara¹⁵, Takashi Kida¹⁶, Yoshia Miyawaki⁸, Yusuke Matsuo^{17

18}, Takahisa Onishi¹⁹, Keisuke Nishimura²⁰, Kiyoshi Migita⁵

Affiliations

¹ Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan naoki-11@fmu.ac.jp.
² Department of Internal Medicine, Showa Medical university, Tokyo, Japan.
³ Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan.
⁴ Research Administration Center, Showa Medical University, Tokyo, Japan.
⁵ Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
⁶ Fukushima Medical University School of Medicine, Fukushima, Japan.
⁷ Kochi Medical School, Kochi, Japan.
⁸ Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁹ Department of Rheumatology, Shimane University Faculty of Medicine, Shimane, Japan.
¹⁰ Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
¹¹ Clinical Laboratory Department, Yokohama City University Hospital, Kanagawa, Japan.
¹² Center for Rheumatic Diseases, Yokohama City University Medical Center, Kanagawa, Japan.
¹³ Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
¹⁴ Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Nagano, Japan.
¹⁵ Department of Rheumatology, Yokohama Rosai Hospital, Kanagawa, Japan.
¹⁶ Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹⁷ Department of Rheumatology, Tokyo Kyosai Hospital, Tokyo, Japan.
¹⁸ Department of Rheumatology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
¹⁹ Department of Rheumatology, Kakogawa Central City Hospital, Hyogo, Japan.
²⁰ Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.

PMID: 40701623
PMCID: PMC12306299
DOI: 10.1136/rmdopen-2025-005558

Safety of mycophenolate mofetil in systemic lupus erythematosus maintenance therapy: insights from the LUNA registry in a nationwide prospective cohort study

Naoki Matsuoka et al. RMD Open. 2025.

. 2025 Jul 22;11(3):e005558.

doi: 10.1136/rmdopen-2025-005558.

Authors

Affiliations

¹ Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan naoki-11@fmu.ac.jp.
² Department of Internal Medicine, Showa Medical university, Tokyo, Japan.
³ Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan.
⁴ Research Administration Center, Showa Medical University, Tokyo, Japan.
⁵ Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
⁶ Fukushima Medical University School of Medicine, Fukushima, Japan.
⁷ Kochi Medical School, Kochi, Japan.
⁸ Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁹ Department of Rheumatology, Shimane University Faculty of Medicine, Shimane, Japan.
¹⁰ Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
¹¹ Clinical Laboratory Department, Yokohama City University Hospital, Kanagawa, Japan.
¹² Center for Rheumatic Diseases, Yokohama City University Medical Center, Kanagawa, Japan.
¹³ Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
¹⁴ Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Nagano, Japan.
¹⁵ Department of Rheumatology, Yokohama Rosai Hospital, Kanagawa, Japan.
¹⁶ Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹⁷ Department of Rheumatology, Tokyo Kyosai Hospital, Tokyo, Japan.
¹⁸ Department of Rheumatology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
¹⁹ Department of Rheumatology, Kakogawa Central City Hospital, Hyogo, Japan.
²⁰ Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.

PMID: 40701623
PMCID: PMC12306299
DOI: 10.1136/rmdopen-2025-005558

Abstract

Objective: We aimed to compare the incidence of severe infections between mycophenolate mofetil (MMF) and other immunosuppressants in patients with systemic lupus erythematosus (SLE) on maintenance therapy using data from the Lupus Registry of Nationwide Institutions in Japan.

Methods: This study employed a prospective cohort design, including patients with SLE undergoing maintenance therapy. Exposure was defined as MMF treatment, and the control group included individuals who received other immunosuppressants (non-MMF) treatments. Severe infections requiring hospitalisation were the primary outcomes, whereas secondary outcomes included all-cause hospitalisation, changes in prednisolone dosage, disease activity and organ damage. Statistical analyses employed marginal structural models with stabilised inverse probability of treatment weighting to adjust for confounders.

Results: The analysis included 1004 patients; the incidence of severe infections was 6.5% in the MMF group and 7.5% in the non-MMF group, with no significant difference (OR 0.69, 95% CI 0.34 to 1.39). Similarly, all-cause hospitalisation rates were comparable between the groups (OR 0.72, 95% CI 0.47 to 1.09). Prednisolone dosage was significantly reduced in the MMF group (-0.66 mg/day, 95% CI -1.09 to -0.23). The organ damage score was modestly reduced in the MMF group (-0.19 points, 95% CI -0.37 to -0.01), whereas the change of disease activity score was comparable between the groups (-0.10 points, 95% CI -0.74 to 0.55).

Conclusions: MMF does not significantly increase the risk of severe infections compared with other immunosuppressants in SLE maintenance therapy. MMF may contribute to reducing the dose of prednisolone.

Keywords: Autoimmune Diseases; Lupus Erythematosus, Systemic; Treatment.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1. Flow diagram of the screening process in the present study. MMF, mycophenolate mofetil; SLE, systemic lupus erythematosus.**

See this image and copyright information in PMC

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Safety of mycophenolate mofetil in systemic lupus erythematosus maintenance therapy: insights from the LUNA registry in a nationwide prospective cohort study

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Safety of mycophenolate mofetil in systemic lupus erythematosus maintenance therapy: insights from the LUNA registry in a nationwide prospective cohort study

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