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Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis.
Cardner, Mathias; Tuckwell, Danny; Kostikova, Anna; Forrer, Pascal; Siegel, Richard M; Marti, Alain; Vandemeulebroecke, Marc; Ferrero, Enrico.
Afiliação
  • Cardner M; Novartis Pharma AG, Basel, Switzerland.
  • Tuckwell D; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Kostikova A; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Forrer P; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Siegel RM; Novartis Pharma AG, Basel, Switzerland.
  • Marti A; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Vandemeulebroecke M; Novartis Pharma AG, Basel, Switzerland.
  • Ferrero E; Novartis Pharma AG, Basel, Switzerland enrico.ferrero@novartis.com marc.vandemeulebroecke@novartis.com.
RMD Open ; 9(2)2023 06.
Article em En | MEDLINE | ID: mdl-37321668
OBJECTIVES: Despite several effective targeted therapies, biomarkers that predict whether a patient with psoriatic arthritis (PsA) will respond to a particular treatment are currently lacking. METHODS: We analysed proteomics data from serum samples of nearly 2000 patients with PsA in placebo-controlled phase-III clinical trials of the interleukin-17 inhibitor secukinumab. To discover predictive biomarkers of clinical response, we used statistical learning with controlled feature selection. The top candidate was validated using an ELISA and was separately assessed in a trial of almost 800 patients with PsA treated with secukinumab or the tumour necrosis factor inhibitor adalimumab. RESULTS: Serum levels of beta-defensin 2 (BD-2) at baseline were found to be robustly associated with subsequent clinical response (eg, American College of Rheumatology definition of 20%, 50% and 70% improvement) to secukinumab, but not to placebo. This finding was validated in two independent clinical studies not used for discovery. Although BD-2 is known to be associated with psoriasis severity, the predictivity of BD-2 was independent of baseline Psoriasis Area and Severity Index. The association between BD-2 and response to secukinumab was observed as early as 4 weeks and maintained up to 52 weeks. BD-2 was also found to predict response to treatment with adalimumab. Unlike in PsA, BD-2 was not predictive of response to secukinumab in rheumatoid arthritis. CONCLUSIONS: In PsA, BD-2 at baseline is quantitatively associated with clinical response to secukinumab. Patients with high levels of BD-2 at baseline reach and sustain higher rates of clinical response after treatment with secukinumab.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Artrite Psoriásica / Beta-Defensinas Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: RMD Open Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Artrite Psoriásica / Beta-Defensinas Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: RMD Open Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça País de publicação: Reino Unido