Interleukin-17 Inhibitors and the Potential Association of Systemic Lupus Erythematosus

Some patients with psoriasis develop lupus erythematosus-like side effects after treatment with interleukin (IL)-17 inhibitors. Whether use of IL-17 inhibitors increases the risk of systemic lupus erythematosus (SLE) remains unclear. This study explores the potential relationship between use of IL-17 inhibitors and the onset of SLE.

Case reports, cohort study, pharmacovigilance study, and 2-sample Mendelian randomization (MR).

Two patients with psoriasis who developed SLE and lupus nephritis (LN) after using IL-17 inhibitors, clinical data from 7,367 patients with psoriasis at Jiangsu Province Hospital, adverse drug reaction reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS), and data from genome-wide association studies related to IL-17A/IL-17 receptor A and SLE.

Use of IL-17 inhibitors.

Development of SLE.

Fisher exact test, reporting odds ratio (ROR), and inverse variance weighting.

Two Chinese patients developed SLE and LN symptoms 2-4 months after receiving IL-17 inhibitor treatment for psoriasis. Kidney biopsy confirmed LN in both patients. A single-center cohort study revealed a significantly higher incidence of lupus among psoriasis patients using IL-17 inhibitors compared to non-users (1.626 vs 0.085 per 1,000 person-years; relative risk, 19.10; 95% confidence intervals [CIs], 1.99-183.47). Pharmacovigilance analysis of the FAERS database indicated an elevated reporting risk of SLE-related adverse reactions associated with IL-17 inhibitors (ROR, 1.62; 95% CI, 1.35-1.95). However, a meta-analysis of MR studies showed that IL-17A (OR, 1.06; 95% CI, 0.89-1.26; P = 0.53) and IL-17 receptor A (OR, 0.98; 95% CI, 0.95-1.02; P = 0.38) were not significantly associated with a decreased risk of SLE.

The case reports and cohort study focus on Asian populations, whereas the FAERS and MR analyses use data from American and European populations.

Use of IL-17 inhibitors might be associated with the increased risk of SLE-like side effects.