Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: a pre-defined, exploratory biomarker analysis from the FORWARD study
| Autor: | Christoph Ladel, Yunyun Luo, Angela A. Manginelli, M. Michaelis, Hans Guehring, Anne-Christine Bay-Jensen, Yi He, Morten A. Karsdal |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Cartilage Articular Male medicine.medical_specialty Anabolism Biomedical Engineering Type II collagen Osteoarthritis Placebo Gastroenterology Injections Intra-Articular Double-Blind Method Rheumatology Internal medicine Synovial Fluid medicine Humans Synovial fluid Orthopedics and Sports Medicine Collagen Type II Aged Aged 80 and over business.industry Cartilage Organ Size Middle Aged medicine.disease Fibroblast Growth Factors Treatment Outcome medicine.anatomical_structure Biomarker (medicine) Female business Biomarkers Sprifermin |
| Zdroj: | Osteoarthritis and Cartilage. 30:92-99 |
| ISSN: | 1063-4584 |
| DOI: | 10.1016/j.joca.2021.10.008 |
| Popis: | Osteoarthritis (OA) is characterized by the gradual loss of cartilage. Sprifermin, a recombinant FGF18, is being developed as a cartilage anabolic drug. PRO-C2 is a serum marker of type II collagen formation and low levels have been shown to be prognostic of radiographic progression. The aim of the study was to investigate whether the patient groups with either high or low PRO-C2 levels responded differently to sprifermin.PRO-C2 was measured in synovial fluid (SF) (n = 59) and serum samples (n = 225) from participants of the FORWARD study, a 2-year phase IIb clinical trial testing the efficacy of intra-articular (IA) sprifermin over placebo. The difference between sprifermin and placebo in respect to in change cartilage thickness (measured by quantitative (q) MRI) was analyzed in groups with either high or low (3SF levels of PRO-C2 increased over time in response to sprifermin, but not to placebo. In the placebo arm, significantly (p = 0.005) more cartilage was lost in the low vs high PRO-C2 group over the 2-year period. The contrast between sprifermin and placebo was significant (p 0.001), ranging from 0.104 mm at week 26 to 0.229 mm at week 104 in the low PRO-C2 group. This result was not significant in the high PRO-C2 group ranging from -0.034 to 0.142.Patients with low serum PRO-C2 levels lost more cartilage thickness over time and grew more cartilage in response to sprifermin vs a placebo when compared to patients with high PRO-C2 levels. |
| Databáze: | OpenAIRE |
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