Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study
Abstract 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;...
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BMC
2024-02-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-024-03285-x |
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| author | Kunihiro Ichinose Shuntaro Sato Takashi Igawa Momoko Okamoto Ayuko Takatani Yushiro Endo Sosuke Tsuji Toshimasa Shimizu Remi Sumiyoshi Tomohiro Koga Shin-ya Kawashiri Naoki Iwamoto Mami Tamai Hideki Nakamura Tomoki Origuchi Nobuyuki Yajima Ken-Ei Sada Yoshia Miyawaki Ryusuke Yoshimi Yasuhiro Shimojima Shigeru Ohno Hiroshi Kajiyama Shuzo Sato Michio Fujiwara Atsushi Kawakami |
| author_facet | Kunihiro Ichinose Shuntaro Sato Takashi Igawa Momoko Okamoto Ayuko Takatani Yushiro Endo Sosuke Tsuji Toshimasa Shimizu Remi Sumiyoshi Tomohiro Koga Shin-ya Kawashiri Naoki Iwamoto Mami Tamai Hideki Nakamura Tomoki Origuchi Nobuyuki Yajima Ken-Ei Sada Yoshia Miyawaki Ryusuke Yoshimi Yasuhiro Shimojima Shigeru Ohno Hiroshi Kajiyama Shuzo Sato Michio Fujiwara Atsushi Kawakami |
| author_sort | Kunihiro Ichinose |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:47:46Z |
| format | Article |
| id | doaj.art-8b489b60467f48bba3b92f09524e6ec3 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-07T14:47:46Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-8b489b60467f48bba3b92f09524e6ec32024-03-05T19:51:58ZengBMCArthritis Research & Therapy1478-63622024-02-012611710.1186/s13075-024-03285-xEvaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort studyKunihiro Ichinose0Shuntaro Sato1Takashi Igawa2Momoko Okamoto3Ayuko Takatani4Yushiro Endo5Sosuke Tsuji6Toshimasa Shimizu7Remi Sumiyoshi8Tomohiro Koga9Shin-ya Kawashiri10Naoki Iwamoto11Mami Tamai12Hideki Nakamura13Tomoki Origuchi14Nobuyuki Yajima15Ken-Ei Sada16Yoshia Miyawaki17Ryusuke Yoshimi18Yasuhiro Shimojima19Shigeru Ohno20Hiroshi Kajiyama21Shuzo Sato22Michio Fujiwara23Atsushi Kawakami24Department of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityClinical Research Center, Nagasaki University HospitalDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Medicine, Division of Hematology and Rheumatology, Nihon University School of MedicineDepartment of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical SciencesDepartment of Internal Medicine, Division of Rheumatology, Showa University School of MedicineDepartment of Clinical Epidemiology, Kochi Medical School, Kochi UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesDepartment of Stem Cell and Immune Regulation, Yokohama City University Graduate School of MedicineDepartment of Medicine (Neurology and Rheumatology), Shinshu University School of MedicineCenter for Rheumatic Diseases, Yokohama City University Medical CenterDepartment of Rheumatology and Applied Immunology Faculty of Medicine, Saitama Medical UniversityDepartment of Rheumatology, Fukushima Medical University School of MedicineDepartment of Rheumatology, Yokohama Rosai HospitalDepartment of Immunology and Rheumatology, Advanced Preventive Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki UniversityAbstract 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.https://doi.org/10.1186/s13075-024-03285-xSystemic lupus erythematosusCalcineurin inhibitorsCancerPropensity scoreIPW |
| spellingShingle | Kunihiro Ichinose Shuntaro Sato Takashi Igawa Momoko Okamoto Ayuko Takatani Yushiro Endo Sosuke Tsuji Toshimasa Shimizu Remi Sumiyoshi Tomohiro Koga Shin-ya Kawashiri Naoki Iwamoto Mami Tamai Hideki Nakamura Tomoki Origuchi Nobuyuki Yajima Ken-Ei Sada Yoshia Miyawaki Ryusuke Yoshimi Yasuhiro Shimojima Shigeru Ohno Hiroshi Kajiyama Shuzo Sato Michio Fujiwara Atsushi Kawakami Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study Arthritis Research & Therapy Systemic lupus erythematosus Calcineurin inhibitors Cancer Propensity score IPW |
| title | Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study |
| title_full | Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study |
| title_fullStr | Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study |
| title_full_unstemmed | Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study |
| title_short | Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry—a historical cohort study |
| title_sort | evaluating the safety profile of calcineurin inhibitors cancer risk in patients with systemic lupus erythematosus from the luna registry a historical cohort study |
| topic | Systemic lupus erythematosus Calcineurin inhibitors Cancer Propensity score IPW |
| url | https://doi.org/10.1186/s13075-024-03285-x |
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