An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis

Abstract

Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

Autologous cell-free serum preparations in the management of knee osteoarthritis: what is the current clinical evidence?

“…Currently, several commercially available kits are utilised to prepare ACS/APS from whole-blood samples of patients [32,38,43]. In general, both ACS and APS are prepared from autologous peripheral blood, the volume of which can vary between 10 and 60 ml depending on the manufacturer kit [20,37,38]. The obtained blood sample is further conditioned by incubation with glass beads and centrifugation, leading to an increase in the production of IL-1Ra as well as multiple other cytokines and growth factors [17,20].…”

“…Furthermore, the number of injections performed is variable ranging between three [37] to six [31,36] over a period of 2-3 weeks. In contrast all the studies [20][21][22] with APS used a single injection of 2.5 ml. Some authors [21,23,39] recommend aspiration of knee prior to injection whilst others have used ultrasound-guided injections [22].…”

“…Additional components of ACS described include platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), insulin-like growth factor (IGF), and fibroblast growth factor (FGF) amongst others [41,44,45]. Hix et al [20] reported the average concentration of IL-1Ra in APS to be 63,740 pg/ml whereas Woodell-May et al [46] noted it to be 30,853 pg/ml. The wide variation in the IL-1Ra levels of ACS and APS reported by the investigators may be due a combination of the production kit and the 24-h incubation period used during the preparation of ACS [47].…”

“…They offer a nonsurgical intraarticular treatment plan at the molecular level which incorporates the inhibition of IL-1b through the rapid induction of IL-1Ra. It has been demonstrated that following interaction with medical-grade concentrator beads, the postconditioned serum level of IL-1Ra is significantly elevated in relation to IL-1b [20,49]. This relative increase alters the relative ratio of IL-1Ra to IL-1b that is essential to restore homeostasis of joints affected by OA [50].…”

“…Several investigators have evaluated the role of autologous cell-free serum preparations like APS [20][21][22] and ACS [23][24][25] in the management of knee OA with human clinical studies following initial in-vitro [18,26] and animal model studies [19,27]. The majority of the available review articles on the topic have summarised the basic science and the results of ACS.…”