The role of Interleukin-17 inhibition in systemic lupus erythematosus – paradoxical hindrance or new therapeutic potential? Results from a Systematic Literature Review and Mendelian Randomization

Deepak Nagra^1*Benajmin Zuckerman¹Joy Odia²Samir Patel¹Melissa Ong¹Maryam Adas¹Zijing Yang¹Katie Bechman¹Mark Russell¹Sijan Bhandari²Chamith Rosa²Siwalik Banerjee²Tim Blake²Nicola Jane Gullick²Ganesh Kasavkar²Chris Wincup^1*

• ¹King's College London, London, United Kingdom
• ²University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom

Systemic lupus erythematosus (SLE) has relatively few licensed treatment options compared with rheumatoid arthritis, axial spondyloarthropathies and psoriatic arthritis. We present findings from a systematic literature review evaluating IL-17 inhibitors (IL17i) in SLE. This includes appraisal of reported treatment efficacy in published cases and assessment of the risk of new-onset SLE following IL17i exposure, using adverse-event data from clinical trials of IL17i in non-SLE indications. Methods A PubMed, EMBASE and MEDLINE search from inception to 30 June 2025 to identify case reports of IL17i-induced SLE. IL17 inhibitors—secukinumab, bimekizumab, brodalumab and ixekizumab—were included. All agents inhibit IL-17A, with bimekizumab also blocking IL-17A/F. Clinical-trial data for secukinumab in psoriasis, psoriatic arthritis and axial spondyloarthritis (from inception to 2024) were reviewed for adverse events relating to new SLE. Case reports of secukinumab used to treat SLE were also reviewed. Results Clinical efficacy in case reports of active SLE: Four published cases describe secukinumab use in patients with known active SLE outside trial settings. The most common indications were active cutaneous lupus and inflammatory arthritis (75%, n=3); one patient (25%) had lupus nephritis. All four were ANA and dsDNA positive. New-onset SLE following IL17i exposure: Across 56 clinical trials of secukinumab, no cases of drug-induced or paradoxical SLE were reported. No cases of SLE have been reported with bimekizumab or ixekizumab, although two cases of ixekizumab-induced lupus tumidus (excluded from this analysis) exist. One case of new-onset SLE has been reported in a patient treated with brodalumab for psoriasis. Six cases of SLE following secukinumab initiation were identified in the literature. Four reports describe secukinumab being used to treat SLE. Conclusion Although rare paradoxical reactions have been described, IL17 inhibitors remain a potential therapeutic option in SLE. All reported cases of IL17i-induced lupus resolved after withdrawal of the agent, with most requiring only symptomatic management. Efficacy data remain extremely limited and heterogeneous, with no standard use of disease-activity metrics such as SLEDAI or DORIS, limiting interpretation. Further translational research and dedicated clinical studies are required to clarify the role of IL-17 in SLE pathogenesis and to define the therapeutic potential of IL17 inhibition.