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Association between serum interleukin‐17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis
Author(s) -
Fitz L.,
Zhang W.,
Soderstrom C.,
Fraser S.,
Lee J.,
Quazi A.,
Wolk R.,
Mebus C. A.,
Valdez H.,
Berstein G.
Publication year - 2018
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.13561
Subject(s) - tofacitinib , etanercept , psoriasis , medicine , interleukin 17 , dermatology , interleukin , immunology , tumor necrosis factor alpha , rheumatoid arthritis , inflammation , cytokine
Summary Background Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)‐17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor‐α inhibitor used in the treatment of psoriasis. Neither agent inhibits IL‐17 directly. Aim To evaluate correlations between circulating IL‐17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. Methods Serum concentrations of IL‐17A homodimer and IL‐17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo ( n = 60), tofacitinib 5 mg twice daily ( n = 184), tofacitinib 10 mg twice daily ( n = 190), or etanercept 50 mg subcutaneously twice weekly ( n = 190). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) and clinical response was defined as patients achieving ≥ 75% improvement from baseline PASI (PASI75). Results Serum levels of IL‐17A homodimer at week 0 showed moderate correlation with PASI, with a Spearman correlation coefficient of 0.43. Furthermore, serum levels of IL‐17A homodimer showed a clear correlation with clinical response, with a decrease of 57.1% in patients achieving PASI75 at week 12, but only 15.9% decrease in nonresponders. PASI75 responders had lower median concentrations of IL‐17A (range across treatments: 0.24–0.27 pg/mL) at week 12 vs. nonresponders (0.37–0.62 pg/mL), regardless of the treatment. Serum IL‐17A/F heterodimer showed similar decreases at week 12 in responders and nonresponders. Conclusions Baseline serum IL‐17A correlates moderately with psoriasis severity. Reduction in circulating IL‐17A is required for disease remission regardless of therapeutic agent.