Tanaka Yoshiya, Atsumi Tatsuya, Aletaha Daniel, Schulze-Koops Hendrik, Fukada Haruhiko, Watson Chris, Takeuchi Tsutomu
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan.
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Rheumatol Ther. 2025 Feb;12(1):53-66. doi: 10.1007/s40744-024-00725-7. Epub 2024 Nov 26.
While modern treatments can prevent progressive bone destruction in patients with rheumatoid arthritis (RA) achieving clinical remission, it is unclear whether residual clinical activity may cause or be associated with progressive joint damage. This post hoc analysis evaluated the association between clinical disease activity and structural progression in patients with RA treated with filgotinib (FIL) in FINCH 1 (NCT02889796).
Patients with RA and inadequate response to methotrexate (MTX) use were randomized 3:3:2:3 to FIL 200 mg (FIL200) or FIL 100 mg (FIL100) once daily, adalimumab 40 mg biweekly, or placebo, all with background MTX. We evaluated the change from baseline (CFB) in modified total Sharp score (mTSS), erosion score, and joint space narrowing score among patients achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8), low disease activity (LDA; 2.8 < CDAI ≤ 10), medium disease activity (MDA; 10 < CDAI ≤ 22), and high disease activity (HDA; CDAI > 22) at 24 weeks.
At week 24, the least squares (LS) mean CFB in mTSS was similarly low across treatments among patients who achieved CDAI remission (range 0.00-0.11) or LDA (n = 285 and 575, respectively). In patients with MDA and HDA (n = 471 and 157, respectively), smaller LS mean CFB in mTSS was seen in the FIL200 group vs. the placebo group (P < 0.05 for both).
RA clinical remission and LDA achievement were associated with suppressed progression of joint destruction over 24 weeks in all treatment groups. Only FIL200 significantly inhibited joint damage compared with placebo in patients with MDA or HDA, indicating an uncoupling of clinical disease activity and structural progression in patients receiving FIL200.
NCT02889796.
虽然现代治疗方法可以预防类风湿关节炎（RA）患者的进行性骨质破坏并实现临床缓解，但尚不清楚残留的临床活动是否会导致或与进行性关节损伤相关。这项事后分析评估了在FINCH 1（NCT02889796）中接受非戈替尼（FIL）治疗的RA患者临床疾病活动与结构进展之间的关联。
对甲氨蝶呤（MTX）治疗反应不足的RA患者按3:3:2:3随机分组，分别接受每日一次200mg非戈替尼（FIL200）或100mg非戈替尼（FIL100）、每两周一次40mg阿达木单抗或安慰剂治疗，所有治疗均联合背景MTX。我们评估了在24周时达到临床疾病活动指数（CDAI）缓解（CDAI≤2.8）、低疾病活动度（LDA；2.8＜CDAI≤10）、中度疾病活动度（MDA；10＜CDAI≤22）和高疾病活动度（HDA；CDAI＞22）的患者中，改良总Sharp评分（mTSS）、侵蚀评分和关节间隙狭窄评分相对于基线的变化（CFB）。
在第24周时，达到CDAI缓解（范围为0.00 - 0.11）或LDA（分别为n = 285和575）的患者中，各治疗组mTSS的最小二乘（LS）平均CFB同样较低。在MDA和HDA患者（分别为n = 471和157）中，FIL200组与安慰剂组相比，mTSS的LS平均CFB更小（两者P均＜0.05）。
在所有治疗组中，RA临床缓解和达到LDA与24周内关节破坏进展受到抑制相关。与安慰剂相比，仅FIL200在MDA或HDA患者中显著抑制了关节损伤，表明接受FIL治疗的患者临床疾病活动与结构进展出现了解耦联。
NCT02889796。
