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Osteoarthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Marc C. Hochberg, Virginia Byers Kraus, Stefan Lohmander, Ali Guermazi, Frank W. Roemer, Ali Mobasheri
Cartilage morphologic quantification requires segmentation of the hyaline cartilage tissue and uses the three-dimensional (3D) nature of MRI datasets to evaluate tissue dimensions (e.g., thickness, volume) as continuous variables (129). Quantitative measurement of cartilage morphology requires high-spatial-resolution 3D imaging sequences that delineate the bone-cartilage interface and cartilage surface with adequate contrast (130). Figure 5.6 shows an example of manual segmentation of knee articular cartilage. Because knees may show both thinning and thickening on a subregional level at the same time, and because the location affected from change in cartilage thickness varies between OA patients, location-independent analyses focusing on the magnitude of change (cartilage thickness gain and loss) independent of their location have been suggested to provide a greater sensitivity to differences in change (131, 132). Quantitative measurements of cartilage volume and thickness change have been used as outcomes in interventional trials, e.g., evaluating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), coxibs (COX-2 selective inhibitors), physical exercise, glucosamine and chondroitin sulfate, strontium ranelate, triamcinolone acetonide, and vitamin D supplementation. More recently, sprifermin showed a dose-dependent positive effect regarding articular cartilage preservation and possibly growth when compared to placebo sustained over a five-year period (57, 58).
Osteoarthritis
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
David Musnick, Richard D. Batson
Fibroblast Growth Factor (FGF): A recombinant FGF-18 (sprifermin) has been used in human trials. There is study evidence that FGF-18 may be efficacious for OA. FGF-18 has been shown in animal models of injury-induced OA to have an anabolic effect on cartilage, stimulating proteoglycan synthesis and cartilage matrix formation (Ellman et al., 2008; Moore et al., 2005).
Emerging injectable therapies for osteoarthritis
Published in Expert Opinion on Emerging Drugs, 2022
Sprifermin is a recombinant form of human FGF18 which is thought to stimulate chondrocytes and hyaline extracellular matrix synthesis [42]. In a multicenter RCT comprising over 500 participants with knee OA, 100 µg of intraarticular sprifermin administered every 6 or 12 months demonstrated a significant improvement in tibiofemoral joint cartilage thickness on magnetic resonance imaging after 2 years [89], and in a follow-up study, these results were sustained at 5 years [90]. Despite these radiographic changes, there was no statistically significant difference in patient-reported pain and function with spifermin-treatment compared to placebo. In a post hoc subgroup analysis of patients with narrower joint space and higher pain scores at baseline; however, there was a significant improvement in pain after 3 years which was sustained at 5 years. In addition, no one who received 100 µg of intraarticular sprifermin underwent target joint arthroplasty over the 5-year period [90].
Investigational drugs for the treatment of osteoarthritis, an update on recent developments
Published in Expert Opinion on Investigational Drugs, 2018
Zhaohua Zhu, Jia Li, Guangfeng Ruan, Guoliang Wang, Cibo Huang, Changhai Ding
Fibroblast growth factor 18 (FGF18) is a growth factor that is known to stimulate chondrogenesis in preclinical models of OA [84]. In 2015, Eckstein et al. performed a post-hoc analysis of the MRI data to determine if sprifermin could reduce cartilage loss. They found that mean cartilage thinning sum score was significantly less in the subjects treated with 100 µg of sprifermin compared to the placebo group [85]. A recent post-hoc analysis demonstrated that sprifermin slowed down cartilage damage from baseline to 12 months in the patellofemoral compartments and improved bone marrow lesions (BMLs) from 6 to 12 months [86]. Hochberg et al. [87] reported that sprifermin was effective in increasing cartilage thickness in a dose-dependent manner in knee OA patients over 3-year follow-up, with acceptable safety profile. In contrary, Dahlberg et al. [88] performed a study of intra-articular injection of sprifermin in patients with advanced knee OA. The authors found no significant changes in cartilage parameters as measured by MRI between 300 µg of sprifermin and placebo groups.
Sprifermin: a recombinant human fibroblast growth factor 18 for the treatment of knee osteoarthritis
Published in Expert Opinion on Investigational Drugs, 2021
Jia Li, Xiaoshuai Wang, Guangfeng Ruan, Zhaohua Zhu, Changhai Ding
Sprifermin (see Box 1) is a recombinant human fibroblast growth factor 18 (rhFGF18) for the treatment of knee OA developed by Merck and Nordic Bioscience, and can both induce chondrocytes proliferation and stimulate ECM synthesis [8]. Therefore, sprifermin is a promising DMOAD and is now a leading investigational agent targeting articular cartilage. This review aims to discuss up-to-date developments of sprifermin for knee OA treatment in both experimental and clinical studies.