Summary

Arthrosamid injection for knee osteoarthritis provides meaningful clinical benefit. Early analysis suggests an anti-inflammtory mechanism, but further detailed analysis will be presented.

Abstract

Introduction

Osteoarthritis(OA) is a major contributor to morbidity worldwide. Injectables are one of a number of non-surgical treatments available to help control symptoms. Arthrosamid® is a non-absorbable, biocompatible, injectable, transparent hydrogel comprising of 97.5% water and 2.5% of cross-linked polyacrylamide. It is indicated for the treatment of osteoarthritis of the knee and has demonstrated clinical benefit compared to Hyaluronic acid. The mechanism of action is currently unknown

The aim of this study was to confirm the clinical effectiveness of Arthrosamid for Knee OA and to investigate its potential mechanism of action.

Methods

Patients were recruited prospectively and underwent 6ml injection of Arthrosamid into the knee joint.

Inclusion criteria
1. Radiological OA greater than Kellgren-Lawrence (K-L) grading scale 2
2. A knee pain score of greater than 40/100 on a visual analogue scale (VAS).
5. No surgery or injection within 12 months.

Exclusion criteria
1. Previous trauma with significant alteration in bone architecture
2. Joint re-placement operation on the other knee
3. Inflammatory arthritis (i.e., rheumatoid arthritis, spondylarthritis and gout)

The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 6 months post injection. Secondary outcomes measures were KOOS score and adverse events.

Synovial fluid (SF) assessment.
SF was collected from patients’ knee joints immediately prior to injection and again at 3 months. Blood samples were also be collected and along with the SF stored in -196˚C liquid nitrogen until analysed. ELISA for specific biomarkers ADAMTS-4 activity, IL-6, sCD14, MMP1 and MMP3 were performed. In addition, a comparative proteomic analysis was performed between “responders” and “non-responders”. A responder was defined as a patient whose 6-month change from baseline in total WOMAC score exceeded the MIC of 20 points.

Results

62 patients totalling 68 knees were recruited. 33 males and 29 females with a mean age of 54.95yrs (35-76). A total of 7 knees were withdrawn during the study leaving a total of 61 knees. The Mean WOMAC score improved from a pre-operative 45.7 (SD17.99) to 30.4 (21.78) at 3 months, 24.8 (SD 22.7) at 6 months and 21.9 (SD 20.24) at 12 months (p0.0001). The mean KOOS score improved from a pre-operative 37 (15.9) to 53(21.1) at 3 months, 56(SD 22.7) at 6 months and 60 (SD 21.4) at 12 months (p0.0001). There were 40 adverse events related to the injection, most commonly arthralgia and swelling.
Early analysis of synovial fluid has demonstrated an anti-inflammatory mode of action in responders. A full bioinformatic analysis will be presented.

Conclusion

Intra-articular injection of Arthrosamid provides clinically meaningful improvements in patients with knee osteoarthritis with an overall response rate at 6 months of 76%. Preliminary synovial fluid analysis has indicated an anti-inflammatory mechanism; however a detailed analysis is currently being performed and will be presented.