Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

被引:16
作者
Fitz, L. [1 ]
Zhang, W. [1 ]
Soderstrom, C. [2 ]
Fraser, S. [2 ]
Lee, J. [1 ]
Quazi, A. [1 ]
Wolk, R. [3 ]
Mebus, C. A. [4 ]
Valdez, H. [4 ]
Berstein, G. [5 ]
机构
[1] Pfizer Early Clin Dev, Cambridge, MA USA
[2] Pfizer Early Clin Dev, Groton, CT USA
[3] Pfizer Global Innovat Pharmaceut, Groton, CT USA
[4] Pfizer Global Innovat Pharmaceut, New York, NY USA
[5] Pfizer Inflammat & Immunol Res Unit, 1 Portland St, Cambridge, MA 02139 USA
关键词
IL-17; ARTHRITIS; SKIN; CYTOKINES; BIOMARKER; ALPHA;
D O I
10.1111/ced.13561
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
BackgroundPsoriasis 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- inhibitor used in the treatment of psoriasis. Neither agent inhibits IL-17 directly. AimTo evaluate correlations between circulating IL-17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. MethodsSerum 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). ResultsSerum 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. ConclusionsBaseline serum IL-17A correlates moderately with psoriasis severity. Reduction in circulating IL-17A is required for disease remission regardless of therapeutic agent.
引用
收藏
页码:790 / 797
页数:8
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