Objective Infection remains a leading cause of mortality in systemic lupus erythematosus (SLE), this study aimed to evaluate the impact of tacrolimus (TAC) use on infection risk in SLE patients. Methods A nested case–control study analyzed 3,176 SLE patients (1,509 infection cases; 1,667 controls) from SLE cohort (2010–2021). TAC exposure was defined as ≥ 30 consecutive days of use within 12 months preceding infection diagnosis or index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for associations between TAC use and infections risk. Drug combination effects of TAC was analyzed with cyclophosphamide (CYC), mycophenolate mofetil (MMF), hydroxychloroquine (HCQ), and glucocorticoids. Results After controlling for confounders (adjusted OR, 95% CI), TAC use was associated with a 60% lower overall infection risk versus other conventional immunosuppressants (0.40, 0.30–0.51), with stronger reductions in bacterial (0.50, 0.37–0.67) and skin/mucosal infections (0.30, 0.13–0.72). Significantly lower risks were observed at lower dosages (≤ 2 mg/d, OR 0.34, 0.24–0.47) and with prolonged use (> 365 days, OR 0.29, 0.19–0.46). Subgroup analyses confirmed enhanced protection in high-risk populations, such as severe disease activity (SLEDAI-2 K > 12, OR 0.32, 0.22–0.46) and CNS involvement (0.25, 0.09–0.71). TAC-HCQ co-therapy reduced infection risk (0.37, 0.27–0.52); separately, TAC counteracted glucocorticoid-associated risk (0.48, 0.30–0.77), and attenuated CYC/MMF-related risk (1.31, 0.83–2.06 vs. 4.25, 2.53–7.13 for CYC-MMF combinations). Conclusions TAC offers superior infection prevention versus other conventional immunosuppressants in SLE, advocating for TAC-centered regimens to optimize risk–benefit profiles.<Table Float="No" ID="Taba"> <tgroup align="left" cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • TAC use was associated with lower infection risk compared to other conventional immunosuppressants, particularly for bacterial infections and skin/mucosal infections. • Dose-response relationships were identified between both TAC dosage and duration of use and lower infection risk in SLE patients. </entry> </row> </tbody> </tgroup> </Table>

Tacrolimus associated with lower infection risk compared to conventional immunosuppressants in systemic lupus erythematosus: real-world evidence

期刊论文
发表日期：

2025年11月19日

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Hanze Zhu,
Ziyi Jin,
Yong Luo,
Xiaojun Tang,
Wei Shen,
Huayong Zhang,
Dandan Wang,
Xuebing Feng,
Lingyun Sun

摘要

Objective

Infection remains a leading cause of mortality in systemic lupus erythematosus (SLE), this study aimed to evaluate the impact of tacrolimus (TAC) use on infection risk in SLE patients.

Methods

A nested case–control study analyzed 3,176 SLE patients (1,509 infection cases; 1,667 controls) from SLE cohort (2010–2021). TAC exposure was defined as ≥ 30 consecutive days of use within 12 months preceding infection diagnosis or index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for associations between TAC use and infections risk. Drug combination effects of TAC was analyzed with cyclophosphamide (CYC), mycophenolate mofetil (MMF), hydroxychloroquine (HCQ), and glucocorticoids.

Results

After controlling for confounders (adjusted OR, 95% CI), TAC use was associated with a 60% lower overall infection risk versus other conventional immunosuppressants (0.40, 0.30–0.51), with stronger reductions in bacterial (0.50, 0.37–0.67) and skin/mucosal infections (0.30, 0.13–0.72). Significantly lower risks were observed at lower dosages (≤ 2 mg/d, OR 0.34, 0.24–0.47) and with prolonged use (> 365 days, OR 0.29, 0.19–0.46). Subgroup analyses confirmed enhanced protection in high-risk populations, such as severe disease activity (SLEDAI-2 K > 12, OR 0.32, 0.22–0.46) and CNS involvement (0.25, 0.09–0.71). TAC-HCQ co-therapy reduced infection risk (0.37, 0.27–0.52); separately, TAC counteracted glucocorticoid-associated risk (0.48, 0.30–0.77), and attenuated CYC/MMF-related risk (1.31, 0.83–2.06 vs. 4.25, 2.53–7.13 for CYC-MMF combinations).

Conclusions

TAC offers superior infection prevention versus other conventional immunosuppressants in SLE, advocating for TAC-centered regimens to optimize risk–benefit profiles.

Key Points

• TAC use was associated with lower infection risk compared to other conventional immunosuppressants, particularly for bacterial infections and skin/mucosal infections.

• Dose-response relationships were identified between both TAC dosage and duration of use and lower infection risk in SLE patients.