F W Roemer1, J Kraines2, A Aydemir2, S Wax2, M C Hochberg3, M D Crema4, A Guermazi5. 1. Boston University School of Medicine, Boston, MA, USA; University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: froemer@bu.edu. 2. EMD Serono, Inc., Billerica, MA, USA, a business of Merck KGaA, Darmstadt, Germany. 3. University of Maryland School of Medicine, Baltimore, MD, USA. 4. Boston University School of Medicine, Boston, MA, USA; Institute of Sports Imaging, French National Institute of Sports, Paris, France. 5. Boston University School of Medicine, Boston, MA, USA; Department of Radiology, VA Boston Healthcare System, West Roxbury, MA, 02132, USA.
Abstract
OBJECTIVE:Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. DESIGN:Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 μg or 100 μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. RESULTS:549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 μg q6mo vs placebo; mean DSM (95% confidence interval [CI]) -0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 μg q6mo vs placebo; mean DSM (95% CI) -0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis. CONCLUSIONS: Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.
RCT Entities:
OBJECTIVE: Sprifermin (recombinant humanfibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. DESIGN:Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 μg or 100 μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. RESULTS: 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 μg q6mo vs placebo; mean DSM (95% confidence interval [CI]) -0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 μg q6mo vs placebo; mean DSM (95% CI) -0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis. CONCLUSIONS: Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.
Authors: Jason S Kim; Silvana Borges; Daniel J Clauw; Philip G Conaghan; David T Felson; Thomas R Fleming; Rachel Glaser; Elizabeth Hart; Marc Hochberg; Yura Kim; Virginia B Kraus; Larissa Lapteva; Xiaojuan Li; Sharmila Majumdar; Timothy E McAlindon; Ali Mobasheri; Tuhina Neogi; Frank W Roemer; Rebecca Rothwell; Robert Shibuya; Jeffrey Siegel; Lee S Simon; Kurt P Spindler; Nikolay P Nikolov Journal: Semin Arthritis Rheum Date: 2022-07-14 Impact factor: 5.431
Authors: Sebastián Cruz Rodriguez-García; Raul Castellanos-Moreira; Jacqueline Uson; Esperanza Naredo; Terence W O'Neill; Michael Doherty; Mikael Boesen; Hemant Pandit; Ingrid Möller Parera; Valentina Vardanyan; Lene Terslev; Will Uwe Kampen; Maria Antonieta D'Agostino; Francis Berenbaum; Elena Nikiphorou; Irene Pitsillidou; Jenny de la Torre-Aboki; Loreto Carmona Journal: RMD Open Date: 2021-06