Sprifermin Increases Cartilage Thickness, Reduces Loss in Knee OA
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Sprifermin increased cartilage thickness and reduced cartilage loss among patients with knee OA, according to data published in the Annals of the Rheumatic Disorders.
“Clinical studies support the structure-modifying effects of the recombinant human fibroblast growth factor, sprifermin, in knee OA,” Felix Eckstein, MD, of the Paracelsus Medical University’s Institute of Anatomy and Cell Biology, in Austria, and colleagues wrote. “The 2-year primary analysis of the phase 2 FORWARD study demonstrated statistically significant dose-dependent modification of cartilage thickness change by quantitative MRI in the total femorotibial joint (TFTJ), and (central) medial and lateral femorotibial compartments with intra-articular (i.a.) sprifermin.”
“Location-independent methods were used in a 1-year, placebo-controlled, proof-of-concept phase 1b study, which suggested that i.a. sprifermin reduced cartilage loss in addition to increasing cartilage thickness,” they added. “However, this used a small sample size, and the extent to which structure modification affected the cartilage thinning score compared with healthy subjects was not studied.”
To determine whether sprifermin reduces cartilage loss and increases cartilage thickness independent of location, Eckstein and colleagues conducted a post-hoc, exploratory analysis using thinning/thickening scores and ordered values calculated from the larger FORWARD study. According to the researchers, FORWARD was a 5-year, multicenter, randomized, double-blind, placebo-controlled, dose-finding, phase 2 study. Investigators randomly assigned equally across five groups patients aged 40to 85 years with knee OA and a medial minimum joint space width 2.5mm or greater in the target knee.
Eighty-three participants received once-weekly injections of 30µg sprifermin every 6 months, while 92 received 30µg sprifermin every 12 months, 100 received treatment with 100µg sprifermin every 6 months, another 100 received 100µg sprifermin every 12 months, and 83 received a placebo. For their own study, Eckstein and colleagues used thinning/thickening scores and ordered values to analyze femorotibial cartilage thickness changes from baseline to 24 months, independent of location. These changes were indirectly compared with those of health individuals enrolled in the Osteoarthritis Initiative.
According to the researchers, thinning scores were significantly lower among participants who received 100µg sprifermin every 6 months, compared with placebo (mean difference: 334µm; 95% CI, 114-554), with a similar cartilage thinning score to healthy individuals.
Further, thickening scores were significantly greater among those treated with 100µg every 6 months (mean difference: 425µm; 95% CI, 267-584), 100µg every 12 months (mean difference: 450µm; 95% CI, 305-594), and 30µg every 6 months (mean difference: 139µm; 95% CI, 19-259), compared with placebo. Thickening scores among these groups were more than doubled compared with healthy individuals.
“The current results support the concept that sprifermin increases cartilage thickness, and reduces cartilage loss,” Eckstein and colleagues wrote. “They expand the primary FORWARD results, showing structural modification of cartilage thickness with sprifermin. Sprifermin should be evaluated further in clinical trials as a potential DMOAD for knee OA.” – by Jason Laday
Disclosures: Eckstein reports being CEO of Chondrometrics GmbH, as well as receiving consulting fees from Merck, Samumed, AbbVie, Bioclinica, Kolon TissueGene, Servier, Galapagos, Novartis and Roche. Please see the study for all other authors’ relevant financial disclosures.
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David A. McLain, MD, FACP, FACR
The prevention and reversal of osteoarthritis has been a major hurdle in rheumatology. Researchers have tried to find a disease modifying osteoarthritis drug (DMOAD) that will reverse structural changes (loss of articular cartilage) and improve function. However, no DMOAD has yet been approved in the United States or Europe.
Although our current therapies help with symptoms, they do not reverse the disease. Yet clinical studies have shown the structure-modifying effects of the recombinant human fibroblast growth factor 18 (FGF-18), sprifermin, in knee OA. In this post-hoc analysis of the 5-year phase II FGF-18 Osteoarthritis Trial (FORWARD) study, the researchers demonstrated a dose-dependent and statistically significant less cartilage thinning with the highest dose of sprifermin.
The researchers also calculated thickening:thinning score ratios and the highest dose of sprifermin had the highest ratio, indicating the biggest effect on cartilage. Thinning scores with sprifermin 100 µg every 6 months were approaching those observed in OAI healthy reference patients, whereas thickening scores were more than doubled. The FORWARD trial did not correlate the thickening:thinning score changes to pain and/or inflammation changes.
This is fascinating work that is progressing. Although this is encouraging, it will be some time before we have an alternative to total joint replacement. Additionally, it is not clear whether increases in thickening:thinning ratios with sprifermin are clinically meaningful. Studies with regards to the effect on pain and inflammation are likely next.
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