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. 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. 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). 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.

中文翻译：

---

评估钙调神经磷酸酶抑制剂的安全性：LUNA 登记系统性红斑狼疮患者的癌症风险——一项历史队列研究

先前的研究显示，与健康个体相比，系统性红斑狼疮 (SLE) 患者的癌症发病率存在相互矛盾的证据。钙调磷酸酶抑制剂（CNI）如环孢素和他克莫司已广泛用于治疗系统性红斑狼疮；然而，它们对癌症风险的影响仍不清楚。我们的目的是调查 SLE 患者的癌症发病率，并确定 CNI 使用与癌症风险之间的潜在关联。全国机构狼疮登记处 (LUNA) 中狼疮患者的癌症标准化发病率 (SIR) 是根据日本厚生劳动省报告的年龄标准化癌症发病率计算的。我们还研究了 CNI 暴露与癌症风险之间的关联，同时考虑了潜在的混杂因素。该分析考虑了一些混杂变量，例如年龄、性别、吸烟史、糖皮质激素最大剂量、环磷酰胺治疗史、持续服用羟氯喹、系统性狼疮国际合作诊所/美国风湿病学院损伤指数 (SDI) 值（不包括癌症发生）、合并症糖尿病史和吸烟史。该研究纳入了 704 名 SLE 患者（625 名女性；88.8%），中位年龄为 44 岁[四分位距 (IQR) = 34-55] 岁。过去最大糖皮质激素剂量的中位数为 40 毫克/天 [IQR = 30–60 毫克/天]，登记时的 SDI 为 1 [IQR = 0–2]。在患者中，246 名（35.1%）有吸烟史，38 名（5.4%）出现癌症并发症。妇科恶性肿瘤占所有癌症的63.2%。 LUNA 队列中癌症的 SIR 为 1.08（95% 置信区间 [CI] = 0.74–1.43）。未发现与 CNI 治疗史相关的具有统计学意义的癌症风险；使用多元逻辑回归的比值比为 1.12 (95% CI = 0.42–3.00)，使用标准化的风险比为 1.18 (95% CI = 0.47–2.16)，使用逆概率加权的风险比为 1.8 (95% CI = 0.41–4.66）。 LUNA 队列中 SLE 患者的癌症发病率与普通人群没有显着差异。这些发现表明，该队列中的 CNI 治疗并未构成癌症发展的危险因素。