PMID- 38347556
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240226
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 26
IP  - 1
DP  - 2024 Feb 12
TI  - Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients 
      with systemic lupus erythematosus from the LUNA registry-a historical cohort 
      study.
PG  - 48
LID - 10.1186/s13075-024-03285-x [doi]
LID - 48
AB  - BACKGROUND: Previous studies have shown conflicting evidence regarding the 
      incidence of cancer in patients with systemic lupus erythematosus (SLE) compared 
      with that in healthy individuals. Calcineurin inhibitors (CNIs) such as 
      cyclosporine and tacrolimus have been widely used to treat SLE; however, their 
      effects on cancer risk remain unclear. We aimed to investigate the incidence of 
      cancer in patients with SLE and determine the potential association between CNI 
      use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer 
      among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) 
      was calculated based on the age-standardized incidence rate of cancer reported by 
      Japan's Ministry of Health, Labour and Welfare. We also examined the association 
      between CNI exposure and cancer risk, while considering potential confounding 
      factors. The analysis accounted for confounding variables such as age, sex, 
      smoking history, maximum glucocorticoid dose, treatment history with 
      cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International 
      Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value 
      (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking 
      history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) 
      with a median age of 44 years [interquartile range (IQR) = 34-55] years. The 
      median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and 
      the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had 
      smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological 
      malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA 
      cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically 
      significant risks of cancer were found in relation to CNI treatment history; the 
      odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the 
      risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk 
      ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). 
      CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did 
      not significantly differ from that in the general population. These findings 
      suggest that CNI treatment in this cohort did not pose a risk factor for cancer 
      development.
CI  - (c) 2024. The Author(s).
FAU - Ichinose, Kunihiro
AU  - Ichinose K
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. 
      kichinose@med.shimane-u.ac.jp.
AD  - Department of Rheumatology, Shimane University Faculty of Medicine, 89-1 
      Enya-Cho, Izumo, 693-8501, Japan. kichinose@med.shimane-u.ac.jp.
FAU - Sato, Shuntaro
AU  - Sato S
AD  - Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan.
FAU - Igawa, Takashi
AU  - Igawa T
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Okamoto, Momoko
AU  - Okamoto M
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Takatani, Ayuko
AU  - Takatani A
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Endo, Yushiro
AU  - Endo Y
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Tsuji, Sosuke
AU  - Tsuji S
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Shimizu, Toshimasa
AU  - Shimizu T
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Sumiyoshi, Remi
AU  - Sumiyoshi R
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Koga, Tomohiro
AU  - Koga T
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Kawashiri, Shin-Ya
AU  - Kawashiri SY
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Iwamoto, Naoki
AU  - Iwamoto N
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Tamai, Mami
AU  - Tamai M
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Nakamura, Hideki
AU  - Nakamura H
AD  - Department of Medicine, Division of Hematology and Rheumatology, Nihon University 
      School of Medicine, Tokyo, Japan.
FAU - Origuchi, Tomoki
AU  - Origuchi T
AD  - Department of Rehabilitation Sciences, Nagasaki University Graduate School of 
      Biomedical Sciences, Nagasaki, Japan.
FAU - Yajima, Nobuyuki
AU  - Yajima N
AD  - Department of Internal Medicine, Division of Rheumatology, Showa University 
      School of Medicine, Shinagawa-Ku, Tokyo, Japan.
FAU - Sada, Ken-Ei
AU  - Sada KE
AD  - Department of Clinical Epidemiology, Kochi Medical School, Kochi University, 
      Nankoku, Japan.
FAU - Miyawaki, Yoshia
AU  - Miyawaki Y
AD  - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama 
      University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, 
      Okayama, Japan.
FAU - Yoshimi, Ryusuke
AU  - Yoshimi R
AD  - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate 
      School of Medicine, Yokohama, Japan.
FAU - Shimojima, Yasuhiro
AU  - Shimojima Y
AD  - Department of Medicine (Neurology and Rheumatology), Shinshu University School of 
      Medicine, Matsumoto, Japan.
FAU - Ohno, Shigeru
AU  - Ohno S
AD  - Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, 
      Japan.
FAU - Kajiyama, Hiroshi
AU  - Kajiyama H
AD  - Department of Rheumatology and Applied Immunology Faculty of Medicine, Saitama 
      Medical University, Saitama, Japan.
FAU - Sato, Shuzo
AU  - Sato S
AD  - Department of Rheumatology, Fukushima Medical University School of Medicine, 
      Fukushima, Japan.
FAU - Fujiwara, Michio
AU  - Fujiwara M
AD  - Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.
FAU - Kawakami, Atsushi
AU  - Kawakami A
AD  - Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, 
      Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240212
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Glucocorticoids)
SB  - IM
MH  - Female
MH  - Humans
MH  - Adult
MH  - Middle Aged
MH  - Cohort Studies
MH  - Calcineurin Inhibitors/adverse effects
MH  - Glucocorticoids/therapeutic use
MH  - *Lupus Erythematosus, Systemic/complications/drug therapy/epidemiology
MH  - Risk Factors
MH  - Registries
MH  - *Neoplasms/chemically induced/epidemiology
MH  - Severity of Illness Index
PMC - PMC10860233
OTO - NOTNLM
OT  - Calcineurin inhibitors
OT  - Cancer
OT  - IPW
OT  - Propensity score
OT  - Systemic lupus erythematosus
COIS- The authors declare no competing interests.
EDAT- 2024/02/13 00:42
MHDA- 2024/02/14 12:49
PMCR- 2024/02/12
CRDT- 2024/02/12 23:45
PHST- 2023/10/16 00:00 [received]
PHST- 2024/02/03 00:00 [accepted]
PHST- 2024/02/14 12:49 [medline]
PHST- 2024/02/13 00:42 [pubmed]
PHST- 2024/02/12 23:45 [entrez]
PHST- 2024/02/12 00:00 [pmc-release]
AID - 10.1186/s13075-024-03285-x [pii]
AID - 3285 [pii]
AID - 10.1186/s13075-024-03285-x [doi]
PST - epublish
SO  - Arthritis Res Ther. 2024 Feb 12;26(1):48. doi: 10.1186/s13075-024-03285-x.