{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:26:13Z","timestamp":1790717173257,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a disease with few licensed drugs when compared to rheumatoid arthritis, axial spondyloarthropathies, and psoriatic arthritis. We report on results of a systematic literature review of IL-17i in SLE with appraisal of published cases of both efficacy of treatment and the risk of developing new SLE following treatment with IL-17i through investigation of adverse events in the setting of clinical trials of IL-17i in non-SLE indications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a PubMed, EMBASE, and MEDLINE search from inception till 30 June 2025 for case reports of IL-17i\u2013induced SLE. The four EMA-licensed IL-17 inhibitors secukinumab, bimekizumab, brodalumab, and ixekizumab were included for analysis. All four monoclonal antibodies block IL-17A, with bimekizumab having the dual functionality of blocking IL-17A\/F. Furthermore, the clinical trial data for secukinumab in psoriasis, psoriatic arthritis, and axial spondylarthritis from inception till 2024 was reviewed for adverse event reporting of new cases of SLE. Both systemic and cutaneous SLE were reported on. We also reported on secukinumab case reports for treating SLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical efficacy of IL-17i in case reports of active SLE: in the case of patients treated with secukinumab for known active SLE outside of the clinical trial setting (\n                      <jats:italic>n<\/jats:italic>\n                      = 4), the commonest indications for the use of secukinumab were active cutaneous disease and inflammatory arthritis (75%,\n                      <jats:italic>n<\/jats:italic>\n                      = 3), with 25% [\n                      <jats:italic>n<\/jats:italic>\n                      = 1] having lupus nephritis. All four patients had positive serology for ANA and dsDNA. New-onset SLE following IL-17i in the literature: amongst 56 clinical trials for secukinumab, there have been no reports of drug-induced or paradoxical\/new-onset SLE following treatment in the reporting periods for each respective trial (\n                      <jats:italic>n<\/jats:italic>\n                      = 13,000). To date, there are no case reports of bimekizumab- or ixekizumab-induced SLE, although there are two case reports for ixekizumab-induced lupus tumidus, which were excluded from the analysis. One case report exists for new-onset SLE in a patient undergoing treatment with brodalumab for psoriasis, and six cases of SLE following initiation of secukinumab were identified. We identified four of the uses of secukinumab in the treatment of SLE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite a handful of case reports for paradoxical reactions with IL-17i, they remain a potential therapeutic option in SLE. All patients recovered upon cessation of the offending IL-17i, and generally patients with drug-induced lupus only require symptomatic management and withdrawal of the offending agent. The efficacy of IL-17i for use in SLE remains unclear due to the limited data from case reports. Among the case reports there was heterogeneity in the reporting of disease activity with no standardization or the use of classic disease metrics such as the SLEDAI or DORIS, which can provide its own challenge in appreciating the results and validating the findings. In conclusion, this is an area that deserves further investigation. Translational research is needed to better understand the role of IL-17 in the pathogenesis of SLE. Dedicated studies and trials of clinical efficacy are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier 1338317.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1706949","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:19:13Z","timestamp":1773659953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of interleukin-17 inhibition in systemic lupus erythematosus\u2014paradoxical hindrance or new therapeutic potential? Results from a systematic literature review and mendelian randomization"],"prefix":"10.3389","volume":"17","author":[{"given":"Deepak","family":"Nagra","sequence":"first","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]},{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Zuckerman","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Odia","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Patel","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Ong","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Adas","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Yang","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Bechman","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Russell","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijan","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamith","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwalik","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Gullick","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Kasavkar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospitals Coventry and Warwickshire","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Wincup","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.624971","article-title":"Current insights and future prospects for targeting IL-17 to treat patients with systemic lupus erythematosus","volume":"11","author":"Koga","year":"2020","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2015.1037441","article-title":"Interleukin-17 in systemic lupus erythematosus: A comprehensive review","volume":"48","author":"Li","year":"2015","journal-title":"Autoimmunity"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaf536","article-title":"Secukinumab in active lupus nephritis: Results from phase III, randomised, placebo-controlled study (SELUNE) and open-label extension study","author":"Zhao","year":"2025","journal-title":"Rheumatol (Oxford)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S363722","article-title":"Lupus nephritis: current perspectives and moving forward","volume":"15","author":"Lichtnekert","year":"2022","journal-title":"J Inflammation Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1294496","article-title":"Case Report: Effectiveness of secukinumab in systemic sclerosis with early skin progress after autologous hematopoietic stem cell transplantation and end-stage kidney disease","volume":"14","author":"Strunz","year":"2023","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12991","article-title":"Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database","volume":"288","author":"Cohen Aubart","year":"2020","journal-title":"J Intern Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"rkae082","DOI":"10.1093\/rap\/rkae082","article-title":"Paradoxical psoriasis with IL-17 inhibitors","volume":"8","author":"Singla","year":"2024","journal-title":"Rheumatol Adv Pract"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2015-000239","article-title":"Paradoxical reactions under TNF-alpha blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview","volume":"2","author":"Toussirot","year":"2016","journal-title":"RMD Open"},{"key":"B9","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.17198","article-title":"Secukinumab on refractory lupus nephritis","volume":"13","author":"Costa","year":"2021","journal-title":"Cureus"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.11124\/jbisrir-d-19-00099","article-title":"Methodological quality of case series studies: an introduction to the JBI critical appraisal tool","volume":"18","author":"Munn","year":"2020","journal-title":"JBI Evid Synth"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3434","article-title":"Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus","volume":"47","author":"Bentham","year":"2015","journal-title":"Nat Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK Biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S440977","article-title":"Response of psoriasis with systemic lupus erythematosus to secukinumab: A case report and review of the literature","volume":"16","author":"Dai","year":"2023","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318762598","article-title":"A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab","volume":"27","author":"Satoh","year":"2018","journal-title":"Lupus"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/24725625.2020.1717741","article-title":"Treatment of psoriatic arthritis complicated by systemic lupus erythematosus with the IL-17 blocker secukinumab and an analysis of the serum cytokine profile","volume":"4","author":"Sato","year":"2020","journal-title":"Mod Rheumatol Case Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/09612033241242698","article-title":"Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review","volume":"33","author":"Zhou","year":"2024","journal-title":"Lupus"},{"key":"B18","article-title":"Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis","volume":"2","author":"Avila-Ribeiro","year":"2023","journal-title":"ARP Rheumatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab918","article-title":"Secukinumab-induced systemic lupus erythematosus occurring in a patient with ankylosing spondylitis","volume":"61","author":"Koller-Smith","year":"2022","journal-title":"Rheumatol (Oxford)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000001511","article-title":"Secukinumab-induced lupus erythematosus: A case report and literature review","volume":"27","author":"Kaler","year":"2021","journal-title":"J Clin Rheumatol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e13417","DOI":"10.1111\/dth.13417","article-title":"Secukinumab-induced subacute cutaneous lupus erythematosus","volume":"33","author":"Conforti","year":"2020","journal-title":"Dermatol Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2020.02.013","article-title":"Secukinumab-induced chronic discoid lupus erythematosus","volume":"6","author":"Chatzimichail","year":"2020","journal-title":"JAAD Case Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.03.016","article-title":"Drug-induced lupus: Traditional and new concepts","volume":"17","author":"Vaglio","year":"2018","journal-title":"Autoimmun Rev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.03.029","article-title":"Pros and cons of Mendelian randomization","volume":"119","author":"Zhang","year":"2023","journal-title":"Fertil Steril"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/art.40930","article-title":"2019 European league against rheumatism\/American college of rheumatology classification criteria for systemic lupus erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2022.2060168","article-title":"Clinical use of anti-histone antibodies in idiopathic and drug-induced lupus","volume":"45","author":"Lee","year":"2022","journal-title":"Immunol Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab883","article-title":"Easy-BILAG: a new tool for simplified recording of SLE disease activity using BILAG-2004 index","volume":"61","author":"Carter","year":"2022","journal-title":"Rheumatol (Oxford)"},{"key":"B28","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J Rheumatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2023.2202050","article-title":"Association of IL-17 serum levels with clinical findings and systemic lupus erythematosus disease activity index","volume":"46","author":"Ebrahimi Chaharom","year":"2023","journal-title":"Immunol Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.70108","article-title":"IL-17(+)\/IL-10(+) ratio in TCRalphabeta(+) CD4(-) CD8(-) T cells as a marker of disease activity in lupus-prone mice and patients with systemic lupus erythematosus","volume":"7","author":"Imai","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1111\/1756-185X.13844","article-title":"Interleukin-17 in urine and serum of patients with nephritis","volume":"23","author":"Chebotareva","year":"2020","journal-title":"Int J Rheum Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914413","article-title":"Cytokines in systemic lupus erythematosus-focus on TNF-alpha and IL-17","volume":"24","author":"Richter","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32167-6","article-title":"Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study","volume":"392","author":"van Vollenhoven","year":"2018","journal-title":"Lancet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222839","article-title":"Clinical trials in systemic lupus erythematosus: the dilemma-Why have phase III trials failed to confirm the promising results of phase II trials","volume":"82","author":"Lorenzo-Vizcaya","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2015(05)01","article-title":"Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus","volume":"70","author":"Pelicari Kde","year":"2015","journal-title":"Clinics (Sao Paulo)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"156874","DOI":"10.1016\/j.cyto.2025.156874","article-title":"IL-17A, IL-23R, FCGR3A are associated with neuropsychiatric systemic lupus erythematosus susceptibility in pediatric patients with lupus nephritis","volume":"188","author":"Ye","year":"2025","journal-title":"Cytokine"},{"key":"B37","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s12915-025-02398-2","article-title":"Design and development of a bispecific antibody targeting BAFF and IL-17 for systemic lupus erythematosus treatment","volume":"23","author":"Xin","year":"2025","journal-title":"BMC Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/cimb44050127","article-title":"The treatment with interleukin 17 inhibitors and immune-mediated inflammatory diseases","volume":"44","author":"Tiburca","year":"2022","journal-title":"Curr Issues Mol Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24988","article-title":"Causes of death among individuals with systemic lupus erythematosus by race and ethnicity: A population-based study","volume":"75","author":"Taylor","year":"2023","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1617451","article-title":"Enhancing the treatment potential of IL-17 antagonism in lupus nephritis: finding the right partner","volume":"16","author":"Gao","year":"2025","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"crossref","DOI":"10.1111\/ced.14583","article-title":"Brodalumab-induced subacute cutaneous lupus erythematosus","volume":"46","author":"Ang","year":"2021","journal-title":"Clin Exp Dermatol"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.1177\/09612033241242698","article-title":"Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review","volume":"33","author":"Zhou","year":"2024","journal-title":"Lupus"},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.1093\/rheumatology\/keab918","article-title":"Secukinumab-induced systemic lupus erythematosus occurring in a patient with ankylosing spondylitis","volume":"61","author":"Koller-Smith","year":"2022","journal-title":"Rheumatology (Oxford)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1706949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:19:14Z","timestamp":1773659954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1706949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2026.1706949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1706949","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]},"article-number":"1706949"}}