Use of a 2.5% Cross-Linked Polyacrylamide Hydrogel in the Management of Joint Lameness in a Population of Flat Racing Thoroughbreds: A Pilot Study

Abstract

Osteoarthritis is one of the most common disease processes effecting equine athletes, causing up to 60% of all lameness. This prospective longitudinal study reports on the effect of treatment of carpal and metacarpophalangeal joint lameness with 2.5% cross-linked polyacrylamide hydrogel (PAAG). A total of 49 flat-racing Thoroughbreds at a single training facility were included in the study. The results show a significant improvement in lameness grades at weeks 1 (P < .01), 4 (P < .001), 12 (P < .001), and 24 (P < .001) when compared to baseline lameness at week 0. This pilot study suggests that 2.5% cross-linked PAAG is a safe and effective joint treatment for managing joint lameness in Thoroughbred racehorses and warrants further blinded and controlled studies to fully evaluate the efficacy of the 2.5% cross-linked PAAG and its mode of action.

Introduction

Osteoarthritis (OA) is cited as the most important musculoskeletal disorder in both humans and horses [1]. Several medications have been evaluated in the treatment of horses with OA, including nonsteroidal anti-inflammatory drugs (NSAIDs), polysulfated glycosaminoglycans (PSGAGs), corticosteroids, glucosamine, hyaluronic acid, and a combination of the above, along with biological substances such as gene therapy, recombinant or autologous growth factors (platelet-rich plasma and autologous conditioned serum), and stem cells (allogenic and autologous) [2]. The 2.5% cross-linked polyacrylamide hydrogel (PAAG) (Arthramid Vet; Mepivacaine Injection, Ceva Animal Health Pty Ltd, Glenorie, NSW, Australia), is a synthetic, nondegradable hydrogel, which is biocompatible, nontoxic, and has water-exchanging capabilities [3], [4]. The hydrogel has been used in the augmentation of soft tissues, and studies from mice, rats, rabbits, pigs, and humans have shown it exerts its effect by being integrated within the tissue through a combination of vessel in-growth and molecular water exchange [5]. Vessel in-growth begins immediately after gel injection with host macrophages entering the gel, which are unable to engulf the polymer, and it is incorporated into the synovium over a period of approximately 14 days [4]. By day 30 in horse joints, the gel had formed a subsynovial layer, which was traversed by thin strands of connective tissue with vessels and covered by a synovial lining facing the joint cavity [4], with the histological appearance persisting up to 2 years postinjection in horse joints.

Recent clinical trials have investigated the effect of 2.5% cross-linked PAAG on improving clinical signs of equine OA unresponsive to previous treatments, with promising results [6], [7], [8]. Another long-term field study evaluated the efficacy of 2.5% cross-linked PAAG in 43 mostly sport horses with OA, with 82.5% of horses being lame-free at 24 months [9]. A standardized experimental study to explore the efficacy of 2.5% cross-linked PAAG in the treatment of induced OA in a goat model also gave encouraging results, with 3 of 4 being clinically lame-free at 4 months postinjection [10]. Recently an observational pilot study of 118 humans with femoro-tibial joint OA treated with 2.5% cross-linked PAAG showed significant improvement (P < .0001) of OA symptoms, up to 1 year [11].

It has been demonstrated [10] that the joint capsule elasticity and synovial membrane of OA affected goat joints improved following 2.5% cross-linked PAAG intra-articular treatment. A hypothesis as to a mechanism of action of 2.5% cross-linked PAAG is that it may have a stabilizing effect on the joint capsule and synovium, increasing elasticity and tensile strength and a subsequent reduction in mechanoreceptor activation [12]. This could in turn reduce synovitis and subsequent deleterious effects as a result.

The purpose of this study was to report on the effect and persistence of 2.5% cross-linked PAAG (Arthramid Vet; Mepivacaine Injection, Ceva Animal Health Pty Ltd, Glenorie, NSW, Australia) on clinical signs of joint lameness in the metacarpophalangeal (MCP) and carpal (antebrachiocarpal and middle carpal) joints of flat-racing Thoroughbreds, to determine if further, more rigorous studies, are warranted. Our hypothesis was that lameness scores would improve after treatment with 2.5% cross-linked PAAG compared to baseline lameness.

Materials and Methods

The study was conducted between June 1, 2015 and May 31, 2016 at a single Thoroughbred training facility. Horses were selected from those presenting for routine veterinary clinical examination for lameness, using a modified AAEP lameness scale formatted for the study (Table 1). Horses were included in the study based on a confirmed diagnosis of joint lameness in one or more joints associated with clinical signs of joint inflammation (effusion, heat, swelling, pain) and when a positive response…

Results

Forty-nine horses with a total of 89 affected joints satisfied the inclusion and postinclusion exclusion criteria, with Table 3 summarizing the data of the study population. The age of the horses treated was between 3 and 7 years (mean 5 years), and all horses were actively involved in flat-racing. At day zero, 54% (48/89) of the included joints had a radiological grading of zero. Synovitis, early OA without radiographic signs, subchondral bone injury, capsulitis, or intra/periarticular soft…

Discussion

This study demonstrates that intra-articular use of 2.5% cross-linked PAAG in the management of carpal and metacarpophalangeal joint lameness in a flat-racing Thoroughbred group was well tolerated, with no side effects such as joint inflammation or infection, and resulted in 65.3% of horses (32/49) being lame-free at 24 weeks postinjection. In addition to this, there were no subsequent injuries to any treated joint or surrounding soft tissue structures, such as subchondral bone disease,…

Conclusion

This study shows 2.5% cross-linked PAAG is a safe and practical first line treatment option for joint lameness isolated to the metacarpophalangeal and carpal joints of TB racehorses. The percentage of horses that were lame-free at 4 weeks and 24 weeks postinjection was 43% and 62%, respectively, following a single intra-articular injection of 2 mL of a 2.5% cross-linked PAAG. This encouraging clinical impression warrants further investigation, in the format of a double-blind randomized clinical…