Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis

Abstract

Objective To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA). Method We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76–5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26–0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20–0.58; I2 = 49%; P < 0.0001). Changes in the cartilage surface morphology of the medial tibio-femoral joint (MD = −0.30, 95% CI −0.44 to −0.16; I2 = 0%; P < 0.0001) and patello-femoral joint (MD = −0.22; 95% CI −0.37 to −0.07; I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52–2.14; I2 = 48%; P = 0.89). Conclusion The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs)

“… 120 A recent meta-analysis pooling data from eight reports of three original trials confirmed its disease-modifying properties such as improvement in cartilage thickness, volume and morphology. 153 However, it failed to exhibit symptomatic improvement measured by WOMAC subscores. As a note, structure-protective effects may prevent or delay KOA patients from reaching levels of debilitating pain in the long term despite lack of initial symptomatic improvement.…”

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

“…One of them represents a phase II multicenter randomized dose-finding clinical study [121]; clinicaltrials.gov NCT01919164), investigating the intra-articular administration of sprifermin. A meta-analysis of the efficacy and safety of sprifermin injection for knee OA treatment has been published very recently [122]. In parallel, a large number of other cytokine/growth factor therapies are in different phases of clinical trials and it will be interesting to see if any of these treatments will be effective in OA therapy [123,124].…”

Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases

“…Sprifermin has exhibited outstanding prospects in promoting cartilage repair, and intraarticular application of Sprifermin is safe and reliable ( Zeng et al, 2021 ). A comprehensive assessment of the specific role of Sprifermin in promoting cartilage repair and the evaluation of its potential molecular mechanisms are conducive to further improvement of Sprifermin.…”

“…In summary, clinical trials, in vitro experiments and animal experiments all indicate that Sprifermin possesses powerful performance in boosting chondrocyte proliferation and cartilage repair. Sprifermin has exhibited outstanding prospects in promoting cartilage repair, and intraarticular application of Sprifermin is safe and reliable (Zeng et al, 2021). A comprehensive assessment of the specific role of Sprifermin in promoting cartilage repair and the evaluation of its potential molecular mechanisms are conducive to further improvement of Sprifermin.…”

“…Also, it can efficiently inhibit proteolytic enzyme activity (such as MMP-13 and ADAMTS-5) and significantly reduce articular cartilage degeneration ( Hochberg et al, 2018 ; Hochberg et al, 2019 ; Muller et al, 2020 ). Sprifermin is currently in phase III clinical trial, and no local or systemic safety concerns have been reported ( Mori et al, 2014 ; Li et al, 2021 ; Zeng et al, 2021 ). In view of this, we reviewed the unique advantages of Sprifermin in promoting chondrocyte proliferation and ECM synthesis, repairing articular cartilage injury and improving cartilage homeostasis, as well as analyzed its possible molecular mechanisms, aiming to provide an important guidance for the effective prevention and treatment of articular cartilage injury related diseases with OA as a typical example.…”