Peficitinib (ASP015K)可減輕台灣傳統DMARD的反應不佳之類風濕性關節炎患者的疾病症狀：一項III期隨機試驗（RAJ3）的事後分析

Peficitinib (ASP015K) in Taiwanese patients with rheumatoid arthritis and inadequate response to conventional disease-modifying antirheumatic drugs in a phase 3 trial (RAJ3)

目的：Janus激酶（JAK）抑制劑是對傳統療法反應不佳的類風濕性關節炎（RA）患者的治療選擇之一。JAK抑制劑peficitinib過去於其三期臨床試驗研究RAJ3中證明其在亞洲患者中的有效性和安全性。這篇研究的目的是在分析RAJ3臨床試驗中台灣患者次族群的研究結果。研究方法：本研究收錄符合條件年滿20歲患者，患有活動性RA（≥6/68觸痛/疼痛關節[TJC68]和≥6/66關節腫脹[SJC66]），並且對既往的疾病調節抗風濕藥物反應不佳者。於52週的研究中，患者按1:1:1:2隨機分配，分別接受peficitinib 100毫克/天、peficitinib 150毫克/天、安慰劑或etanercept 50毫克/週（etanercept為開放式參考組）；接受安慰劑的患者在第12週轉換使用每天一次的peficitinib 100/150 mg治療。觀察的主要療效是在第12週/提前終止（ET）時的美國風濕病學會（ACR）20的反應。觀察的次要療效包括ACR50/70反應，以及相對於基線時28關節疾病活動評分（DAS28）、TJC68、SJC66以及患者和醫生報告的結果變化。在整個過程中也評估出現的不良事件（TEAE）。結果：在整個研究隨機分配的509名患者中，有38名台灣患者接受了研究藥物。第12週/ET時於peficitinib 100 mg組、peficitinib 150 mg組和安慰劑組的ACR20反應率分別為62.5%、87.5%和25.0%。在大多數時間點，peficitinib與安慰劑相比，於其他療效項目都比第12週/ET的有更大的改善數值。TEAE的發生率與整體研究是一致。結論：此研究發現與整個亞洲研究人群相似，在台灣次族群中，peficitinib是一種有效且有良好耐受性的類風濕性關節炎治療方法。

Objective: Janus kinase (JAK) inhibitors are a treatment option for patients with rheumatoid arthritis (RA) who respond inadequately to conventional therapies. The phase 3 study RAJ3 previously demonstrated the efficacy and safety of the JAK inhibitor peficitinib in Asian patients. We aimed to investigate RAJ3 study outcomes in a subgroup of Taiwanese patients.Methods: Eligible patients were aged≥20 years, had active RA (≥6/68 tender/painful joints [TJC68] and≥6/66 swollen joints [SJC66]), and had an inadequate response to prior disease-modifying antirheumatic drugs. Patients were randomized 1:1:1:2 to 52 weeks of treatment with peficitinib 100 mg/day, peficitinib 150 mg/day, placebo, or etanercept 50 mg/week (open-label reference arm); patients receiving placebo were switched at week 12 to peficitinib 100/150 mg once daily. The primary efficacy variable was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary efficacy variables included ACR50/70 response, and changes from baseline in 28-joint disease activity score (DAS28), TJC68, SJC66, and patient- and physician-reported outcomes. Treatment-emergent adverse events (TEAEs) were assessed throughout. Results: Of 509 patients randomized in the overall study, 38 Taiwanese patients received study drug. ACR20 response rates at week 12/ET were 62.5%, 87.5%, and 25.0% with peficitinib 100 mg, peficitinib 150 mg, and placebo, respectively. Improvements to week 12/ET in other efficacy variables were numerically greater with peficitinib versus placebo at most timepoints. Rates of TEAEs were consistent with the overall population. Conclusion: Similar to the overall Asian study population, peficitinib was an efficacious and well-tolerated treatment for RA in the Taiwanese subgroup.