TREATMENT OF KNEE OSTEOARTHRITIS WITH AUTOLOGOUS CONDITIONED SERUM (ACS): A PROSPECTIVE, RANDOMIZED, PLACEBO-CONTROLLED, PATIENT- AND OBSERVER-BLIND, PARALLEL-DESIGN TRIAL. THERAPEUTIC STUDY, LEVEL I (RANDOMIZED CONTROLLED TRIAL- RCT, ISRCTN: 71311752)

Abstract

Objective: In the absence of dependable and reproducible non-surgical treatment alternatives for osteoarthritis (OA), new approaches are needed. A new therapy, based on the intra-articular injection of autologous conditioned serum (ACS), is used in several European countries. ACS is generated by incubating venous blood with medical grade glass beads. Peripheral blood leukocytes produce elevated amounts of endogenous anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1Ra) that are recovered in the serum(1).

In the present study, the clinical efficacy and safety of intra-articular injections of ACS were compared to intra-articular hyaluronan (HA), and placebo (saline) in patients with confirmed knee OA.

Study Methods: In a prospective, randomized, patient- and observer-blind, placebo-controlled trial with three parallel groups, 399 patient knees with OA were included in an intention to treat (ITT-) analysis. Efficacy was assessed by patient-administered outcome instruments (WOMAC, VAS, SF-8, GPA) after 7, 13 and 26 weeks. The frequency and severity of adverse events were used as safety parameters.

Results: In all treatment groups, intra-articular injections produced a significant reduction in WOMAC-scores and weight-bearing pain (VAS), as well as improvement in health-related quality of life. However, responses to ACS were far stronger. The superiority of ACS and either HA or placebo was statistically significant for all outcome measures and all time points. The mean improvement for patients treated with HA and placebo was half that in the ACS-group (p< 0.001). No significant differences between HA treatment and placebo injections (p> 0,05, at all time points and all outcome measures) were recorded. Frequency of adverse advents (AE) was comparable in the ACS- and the placebo-group (p> 0,05), whereas there were significantly more AE in the HA-group (p< 0,05 for the comparison with ACS and placebo).

Conclusion: Patients with OA of the knee treated by intra-articular injection of ACS showed significantly better clinical improvement during 26 weeks observation compared to patients injected with HA or placebo. The results demonstrate that ACS is highly effective and well tolerated in the management of chronic, idiopathic OA of the knee.

So far, the efficacy of ACS is defined through improvement in clinical signs and symptoms, particularly pain. It remains to be determined whether there are disease-modifying, chondroprotective, or even chondroregenerative, sequelae.