{"doi":"10.1016/j.jaad.2022.04.060","title":"Secukinumab improves mild-to-moderate psoriasis: A randomized, placebo-controlled exploratory clinical trial","abstract":"To the Editor: Many effective biologic treatments have been established for moderate-to-severe psoriasis, defined in most clinical trials as psoriasis with ≥10% body surface area and psoriasis area-and-severity index (PASI) ≥12. Although patients with mild-to-moderate psoriasis constitute 82% of the total psoriasis population, mild-to-moderate psoriasis patients are not permitted entry to clinical trials of newer biologic agents.1Strober B. Ryan C. van de Kerkhof P. et al.Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council.J Am Acad Dermatol. 2020; 82: 117-122Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar In our previous studies comparing gene expression profiles of mild and severe psoriasis, the spectrum of mild-to-severe psoriasis was defined by the common activation of IL-17 pathway genes but with key differences in the immune regulatory gene expression.2Kim J. Bissonnette R. Lee J. et al.The spectrum of mild to severe psoriasis vulgaris is defined by a common activation of IL-17 pathway genes, but with key differences in immune regulatory genes.J Invest Dermatol. 2016; 136: 2173-2182Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Since the expression of immune regulatory genes is high in mild psoriasis, we hypothesized that treatment response and disease remission after IL-17A inhibition differs in mild psoriasis compared with severe psoriasis. To test the efficacy of an IL-17A antagonist in mild-to-moderate psoriasis, we conducted a randomized, double-blinded, placebo-controlled exploratory phase II clinical trial for the use of secukinumab, an IL-17A antagonist, for treatment of mild-to-moderate psoriasis (PASI >6 and <12 and a body surface area <10%; (Supplementary Fig 1 and clinical trial protocol, available via Mendeley at https://data.mendeley.com/datasets/nyhfxz8tt9/1). We also reported the gene expression modifications observed in psoriasis skin (Supplementary experiment protocol, available via Mendeley at https://data.mendeley.com/datasets/nyhfxz8tt9/1). At week 12, secukinumab treatment was more effective than placebo; secukinumab treatment (group 1) of mild-to-moderate psoriasis led to greater rates of PASI75 (72.7% in secukinumab vs 0% in placebo; P < .005), PASI90 (63.6% in secukinumab vs 0% in placebo; P < .005) and Physician Global Assessment 0/1 (81.8% in secukinumab vs 0% in placebo; P < .0005) when compared to placebo (group 2) (Fig 1 and Supplementary Fig 2, available via Mendeley at https://data.mendeley.com/datasets/nyhfxz8tt9/1). Secukinumab treatment of mild-to-moderate psoriasis resulted in more disease improvement than placebo as early as 2 weeks after initiation of treatment (decrease in PASI and Physician Global Assessment at week 2; P < .05). All of the mild-to-moderate psoriasis patients (100%) achieved a PASI75 16 weeks after initiating injections. A gene expression study of skin biopsies revealed that the impact of systemic IL-17A inhibition on psoriasis patients’ skin immunity was not confined to only blocking the major cytokine of pathogenic T cells (IL17A) (Fig 2). It extended to blocking the entire feed-forward amplification loop of psoriasis inflammation. In addition, the gene expression of a keratinocyte stem cell marker (KRT15) and cytokines that may promote skin homeostasis (IL343Lelios I. Cansever D. Utz S.G. Mildenberger W. Stifter S.A. Greter M. Emerging roles of IL-34 in health and disease.J Exp Med. 2020; 217e20190290Crossref PubMed Scopus (49) Google Scholar and IL374Rønholt K. Nielsen A.L.-L. Johansen C. et al.IL-37 Expression is downregulated in lesional psoriasis skin.Immunohorizons. 2020; 4: 754-761Crossref PubMed Scopus (15) Google Scholar) was increased in psoriasis skin after systemic IL-17A inhibition. Our study supports the increasing trend to explore systemic treatments for mild-to-moderate psoriasis. The Delphi consensus from the International Psoriasis Council recommends that psorias","journal":"Journal of the American Academy of Dermatology","year":2022,"id":275247,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":944767,"name":"Jongmi Lee","orcid":null,"position":1,"is_corresponding":false},{"id":912571,"name":"Jason E. Hawkes","orcid":"0000-0001-5870-181X","position":2,"is_corresponding":false},{"id":944369,"name":"Xuan Li","orcid":"0000-0001-7021-8054","position":3,"is_corresponding":false},{"id":944370,"name":"Norma Kunjravia","orcid":"0000-0003-0308-1048","position":4,"is_corresponding":false},{"id":944371,"name":"Darshna Rambhia","orcid":"0000-0002-9789-8077","position":5,"is_corresponding":false},{"id":414214,"name":"Inna Cueto","orcid":"0000-0001-7913-0905","position":6,"is_corresponding":false},{"id":862644,"name":"Ariana Moreno","orcid":null,"position":7,"is_corresponding":false},{"id":778553,"name":"Hong Hur","orcid":"0000-0002-4088-9188","position":8,"is_corresponding":false},{"id":273428,"name":"Sandra Garcet","orcid":"0000-0002-4465-8547","position":9,"is_corresponding":false},{"id":944372,"name":"Wei Zhou","orcid":"0000-0002-5081-4710","position":10,"is_corresponding":false},{"id":94703,"name":"Junyue Cao","orcid":"0000-0003-4097-489X","position":11,"is_corresponding":false},{"id":18939,"name":"James G. Krueger","orcid":"0000-0002-3775-1778","position":12,"is_corresponding":false},{"id":284102,"name":"Jaehwan Kim","orcid":"0000-0002-7586-1425","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T00:28:16.928746Z","pmid":"35551962","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}