Felix Eckstein , Susanne Maschek , Wolfgang Wirth , Christoph Ladel , Asger Reinstrup Bihlet , Chris Knight , Kenneth Somberg , Luping Zhao
{"title":"斯利福明与安慰剂治疗三年后膝关节软骨厚度变化的无偏差分析--2B 期 FORWARD 研究的事后分析","authors":"Felix Eckstein , Susanne Maschek , Wolfgang Wirth , Christoph Ladel , Asger Reinstrup Bihlet , Chris Knight , Kenneth Somberg , Luping Zhao","doi":"10.1016/j.ocarto.2024.100513","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Post-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees.</p></div><div><h3>Methods</h3><p>FORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n = 57 treated with placebo intra-articular injections every 6 months (q6M); n = 69 with 30 μg sprifermin every 12 months (q12 M), n = 67 with 30 μg q6M, n = 73 with 100 μg q12 M, and n = 71 with 100 μg q6M between baseline (BL) and 18 M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus.</p></div><div><h3>Results</h3><p>TFTJ cartilage thickness change during Y2→Y5 was −26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p = 0.80) was observed between Sprifermin treated or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was −8.2 μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. −5.4 μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (<em>t</em>-test).</p></div><div><h3>Conclusion</h3><p>FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.</p><p>This is a post-hoc analysis of the FORWARD trial: <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: NCT01919164.</p></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100513"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665913124000803/pdfft?md5=862e7f47b535b92ba1ddb27a2b95b9d7&pid=1-s2.0-S2665913124000803-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment – A post-hoc analysis from the phase 2B FORWARD study\",\"authors\":\"Felix Eckstein , Susanne Maschek , Wolfgang Wirth , Christoph Ladel , Asger Reinstrup Bihlet , Chris Knight , Kenneth Somberg , Luping Zhao\",\"doi\":\"10.1016/j.ocarto.2024.100513\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Post-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees.</p></div><div><h3>Methods</h3><p>FORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n = 57 treated with placebo intra-articular injections every 6 months (q6M); n = 69 with 30 μg sprifermin every 12 months (q12 M), n = 67 with 30 μg q6M, n = 73 with 100 μg q12 M, and n = 71 with 100 μg q6M between baseline (BL) and 18 M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus.</p></div><div><h3>Results</h3><p>TFTJ cartilage thickness change during Y2→Y5 was −26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p = 0.80) was observed between Sprifermin treated or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was −8.2 μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. −5.4 μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (<em>t</em>-test).</p></div><div><h3>Conclusion</h3><p>FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.</p><p>This is a post-hoc analysis of the FORWARD trial: <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: NCT01919164.</p></div>\",\"PeriodicalId\":74377,\"journal\":{\"name\":\"Osteoarthritis and cartilage open\",\"volume\":\"6 4\",\"pages\":\"Article 100513\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2665913124000803/pdfft?md5=862e7f47b535b92ba1ddb27a2b95b9d7&pid=1-s2.0-S2665913124000803-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Osteoarthritis and cartilage open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2665913124000803\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Osteoarthritis and cartilage open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2665913124000803","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment – A post-hoc analysis from the phase 2B FORWARD study
Objective
Post-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees.
Methods
FORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n = 57 treated with placebo intra-articular injections every 6 months (q6M); n = 69 with 30 μg sprifermin every 12 months (q12 M), n = 67 with 30 μg q6M, n = 73 with 100 μg q12 M, and n = 71 with 100 μg q6M between baseline (BL) and 18 M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus.
Results
TFTJ cartilage thickness change during Y2→Y5 was −26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p = 0.80) was observed between Sprifermin treated or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was −8.2 μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. −5.4 μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (t-test).
Conclusion
FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.
This is a post-hoc analysis of the FORWARD trial: ClinicalTrials.gov Identifier: NCT01919164.
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