注射關節炎新藥sprifermin可恢復軟骨厚度
作者：
小柯機器人發布時間：2019/10/11 10:37:56
美國馬裡蘭大學Marc C. Hochberg研究組的一項最新研究探討了關節內注射新藥Sprifermin與安慰劑對骨關節炎患者股骨脛骨關節軟骨厚度的影響。該研究發表在2019年10月8日出版的《美國醫學會雜誌》上。
FORWARD是一項為期5年、劑量發現、在10個地點進行的多中心隨機臨床試驗。2013年7月至2014年5月，研究組招募了549例年齡在40到85歲之間，患有症狀性膝關節骨性關節炎，Kellgren-Lawrence 2或3級的參與者。將這些參與者隨機分為5組，其中110名每6個月關節內注射100μg Sprifermin，110名每12個月注射100μg Sprifermin，111名每6個月注射30μg Sprifermin，110名每12個月注射30μg Sprifermin，108名每6個月注射一次安慰劑。
共有474名（86.3%）參與者完成了2年的隨訪。治療兩年後，與安慰劑組相比，每6個月注射100μg Sprifermin組的股骨-脛骨關節軟骨總厚度比基線增長了0.05mm，每12個月注射100μg Sprifermin組增長了0.04mm，每6個月注射30μg Sprifermin組增長了0.02mm，每12個月注射30μg Sprifermin組增長了0.01mm。4個Sprifermin治療組的總體WOMAC評分較安慰劑組均無顯著改善。最常見的不良反應是關節痛，但各組間的發生率並無顯著差異。
綜上，對於膝關節骨性關節炎患者，每6個月或12個月注射100μg Sprifermin與安慰劑相比，可顯著改善2年後的股骨-脛骨關節軟骨總厚度，但其臨床意義和緩解的持久性尚不確定。
附：英文原文
Title: Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial
Author: Marc C. Hochberg, Ali Guermazi, Hans Guehring, Aida Aydemir, Stephen Wax, Patricia Fleuranceau-Morel, Asger Reinstrup Bihlet, Inger Byrjalsen, Jeppe Ragnar Andersen, Felix Eckstein
Issue&Volume: Vol 322 No 14
Abstract:
Importance Sprifermin is under investigation as a disease-modifying osteoarthritis drug.
Objective To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.
Design, Setting, and Participants FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported.
Interventions Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks.
Main Outcomes and Measures The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%).
Results Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, −0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, −0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).
Conclusions and Relevance Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.
DOI: 10.1001/jama.2019.14735
Source: https://jamanetwork.com/journals/jama/article-abstract/2752470