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

Abstract

SummaryBackground. 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-a 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.

An analysis of selected factors influencing the efficacy of psoriasis therapy

“…Moreover, they concluded that an increase in IL-17A level even with 1pg/ml predisposed for severe psoriasis [56]. Also, Fitz et al drew attention to the value of assessing IL-17 expression profile in psoriatic patients before commencing an anti-cytokine therapy [57].…”

“…Również Fitz i wsp. zwrócili uwagę na znaczenie określania profilu ekspresji IL-17 u pacjentów z łuszczycą przed rozpoczęciem terapii antycytokinowej [57].…”

Drug resistance in anti-TNF therapy of psoriatic arthritis

“…Etanercept shows an ability to neutralize only a soluble TNF-α, whereas adalimumab neutralizes both free and membrane-bound TNF-α [4,7,9]. Moreover, it is indicated that serum IL-17 concentration prior to a therapy with anti-cytokine drugs, including etanercept, determines the odds for the therapy success [19]. Al-Gareeb et al observed also a lack of adequate response to etanercept in patients suffering from rheumatoid arthritis [20].…”

“…Etanercept ma zdolność neutralizowania tylko rozpuszczonej formy TNF-α, a adalimumab neutralizuje zarówno wolną, jak i związaną z błoną komórkową formę TNF-α [4,7,9]. Wskazuje się również, że stężenie IL-17 w surowicy przed rozpoczęciem terapii lekami antycytokinowymi, w tym etanerceptem, określa szansę powodzenia terapii [19]. Al-Gareeb i wsp.…”

The role of interleukins 17, 23 and antibodies to the thyroid-stimulating hormone receptor in the pathogenesis of endocrine ophthalmopathy

“…Учитывая тот факт, что концентрация ИЛ-17 и АТ к рТТГ напрямую коррелирует с клиническими проявлениями активности ЭОП, их совместное определение в сыворотке крови может дать дополнительную информацию о состоянии аутоиммунитета и использоваться для прогноза течения данного заболевания. Полученные данные по ИЛ-17 сопоста-вимы с результатами исследований как при других аутоиммунных заболеваниях [7,8,15], так и при ЭОП [16].…”