Merck KGaA, Darmstadt, Germany.
EMD Serono Research and Development Institute, Inc., Billerica, MA, USA.
Semin Arthritis Rheum. 2021 Apr;51(2):450-456. doi: 10.1016/j.semarthrit.2021.03.005. Epub 2021 Mar 11.
To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin.
Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40-90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint.
The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]).
Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials.
NCT01919164.
评估在接受 sprifermin 治疗的膝关节骨关节炎患者的 FORWARD 试验中处于进一步进展风险（SAR）的亚组的疼痛结局和软骨厚度变化。
患者按 1:1:1:1:1 的比例随机分为以下 5 组：sprifermin 100μg 每 6 个月（q6mo）、100μg q12mo、30μg q6mo、30μg q12mo 或安慰剂，共治疗 18 个月。SAR 的定义为基线内侧或外侧最小关节间隙宽度（mJSW）为 1.5-3.5mm，以及西部安大略省和麦克马斯特大学骨关节炎指数（WOMAC）疼痛评分为 40-90 分。分析中包括了 3 年的随访。通过重复测量、随时间的线性剂量-效应趋势来探索治疗益处。
SAR 包括 549 例患者中的 161 例（29%）。与 SAR 安慰剂相比，sprifermin 100μg q6mo 治疗的 SAR 患者在第 3 年时 WOMAC 疼痛的平均差值（95%CI）为 -8.75（-22.42，4.92），意向治疗人群为 0.97（-6.22，8.16）。SAR 安慰剂患者在 2 年内比改良意向治疗（mITT）安慰剂组损失更多的软骨（从基线的平均变化，mm[SD]：-0.05[0.10] vs -0.02[0.07]）。与安慰剂相比，sprifermin 100μg q6mo 的总股胫关节厚度净增加（调整后的平均差值[95%CI]）在 SAR 和 mITT 组中相似：0.06[0.01，0.11] vs 0.05[0.03，0.07]）。
选择基线时 mJSW 较低和疼痛中度至高度的患者导致疾病进展更快，并证明了结构修饰的转化（维持总软骨厚度的净获益）为症状获益。该亚组可能代表未来试验的目标人群。
NCT01919164。
