Clinical Application of Arthramid Vet Vol 1, Issue 2. Nov, 2020

In this second issue we report on how an experienced racetrack veterinarian managed a case of chronic tenosynovitis of the deep digital flexor tendon sheath in a racing Thoroughbred.

Case History: An 8 year-old TB racehorse presented with subacute- chronic digital flexor tendon sheath effusion in the right forelimb. The horse had been on and off lame for about 4 months, had mild pain on flexion, a shifting gait at canter and gallop and was reluctant to lead on the affected limb.

The effusion was made worse after fast work, and although it improved temporarily to treatment with triamcinolone/ HA (for 3-4 weeks) , it worsened again with increasing galloping exercise later in its preparation.

Diagnostic Investigation: Radiography and ultrasonography of the fetlock and surrounding structures was performed and detected no abnormal findings (apart from the tenosynovitis). Further diagnostics were offered (MRI, tenoscopy) but declined by the owner’s agent.

Treatment: The area was prepped aseptically and 2mls (50mg) of 2.5% PAAG Arthramid Vet was injected directly into the tendon sheath. This was followed by 3 days of swimming exercise before the horse returned to full work (galloping exercise).

Outcome: Re-examination after 18 days revealed a significant reduction in the degree of tenosynovitis and the horse was no longer reactive to flexion. The track rider reported the horse to be working evenly and would now lead consistently on the affected limb. A prolonged response to treatment was seen under full race training and the horse was racing and winning.

Discussion: There have been no case reports to date on the clinical application of 2.5% PAAG Arthramid Vet® for managing tenosynovitis of the digital flexor tendon sheath.

Ultrasonography is an excellent tool for imaging this area but has relatively low sensitivity for detecting longitudinal tears in the tendon or paratenon of the deep digital flexor tendon itself. This could have been missed and would have carried a worse prognosis without tenoscopy.

Most likely this was a case of primary synovitis of the tendon sheath itself that became chronic over time. This may occur due to poor conformation in conjunction with heavy workloads, or acute injuries that tend to not resolve due to ongoing inflammation of the synovial lining of the tendon sheath.

Wehling et al. (2007) showed mononuclear cells respond to a pyrogenic-free substance, such as 2.5% PAAG, with the release of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist protein, transforming growth factor-1, and insulin-like growth factor 1, amongst many other cytokines1. This may explain the reduction in tenosynovitis seen in this case. It is also known that 2.5% PAAG acts as a dynamic tissue scaffold, integrating into tissues themselves by a combination of cell migration and vessel in growth, that in turn increases tissue elastance2. In articular joints, it is further documented that a new and hypercellular synovial cell lining forms on the internal surface. Therefore, it is possible that administration of 2.5% PAAG Arthramid® Vet in this case resulted in improved function of the tendon sheath and an improvement in the quality of synovial fluid leading to a resolution of the synovitis. Further studies are necessary and should include quantitative assessment of the quality of synovial fluid.

Dr Jason Lowe BVsc, Cert EP, MBA.

References:

1. Wehling, P., Carsten, M., Frisbie, D.D., McIlwraith, C.W. and Kawcak, C.E. (2007) Autologous conditioned serum in the treatment of orthopaedic diseases, the Orthokine therapy. Biodrugs 21, pp. 323-332.
2. Tnibar. A., Persson, A.B. and Jensen, H.E. (2017) Mechanisms of Action of an Intraarticular 2.5% Polyacrylamide Hydrogel in a Goat Model of Osteoarthritis: Preliminary Observations. SM J Biomed Eng. 3(3), 1022.

Clinical Application of Arthramid Vet Vol 1, Issue 1. Oct, 2020

In this first issue we report on how experienced racetrack veterinarians’ have introduced Arthramid Vet into their management of subchondral bone disease in racing Thoroughbreds’.

Introduction: Subchondral bone is composed of a subchondral bone plate and underlying trabecular bone, which together act to dampen forces that are transmitted through the joint. Acute fracture or fragmentation of subchondral bone does occur but is rare as a cause of lameness in equine athletes(1). What we are beginning to understand is that chronic fatigue injury is much more common.

Chronic fatigue injury is a term used to characterize the pathologic processes that start at molecular and biochemical levels, leading to histologic evidence of tissue damage and ultimately tissue failure that results in clinical signs. Chronic fatigue injuries therefore result from cyclic loading of tissues below the biomechanical threshold of tissue failure. This can then lead to a progression of areas of microdamage, areas of tissue weakness, or maladaptation of the tissues resulting in chronic progressive changes to the material properties of the tissue involved, all ultimately leading to pain or injury.

Although the clinical manifestations of chronic fatigue injury are consistent in nature, they can differ between breeds, use and age. It is now understood that chronic fatigue injury consistently occurs in the subchondral bone of equine athletes, and there is evidence to suggest that it occurs in the articular cartilage and, is likely worsened by degradation processes associated with synovitis(2).

Background: Over 60 racing Thoroughbreds with subchondral bone disease were diagnosed and managed by a single veterinary clinic in Australia over a two-year time period. Horses ranged in age from 3 to 5 years.

These cases all presented with poor performance, were often aggressive in their work, and may have had episodes of EIPH on routine post gallop scopes raising the question whether it was pain related. Typically, lameness was bilateral, and even quadruple with a shortened and shuffling gait. The horses were consistently reported to disunite at the canter, and they may or may not react to flexion or have joint effusion but would often plait behind and have speedy cuts.

Diagnosis: Regional analgesia of the palmar/ plantar metacarpal/ metatarsal nerves (2 to 3 mls of 100mg/ml mepivacaine hydrochloride) at the level of the distal canon was performed by the examining veterinarian. They found cases easier to diagnose under ridden work by performing regional analgesia and sending the rider back out to trot/ canter. There was a significant improvement in the gait reported by the track rider and observed by the examining veterinarian.

Radiographic examination included latero-medial, lateral- oblique, medial- oblique, dorso-palmar/ plantar views, flexed DP, 1250 DP, and flexed DP (skyline) views. Changes seen included condylar sclerosis and flattening of the palmar/ plantar condyles. Occasionally a central area of lucency could be observed, most likely subchondral bone collapse. Generally, though radiographs were unreliable for a specific diagnosis.

Scintigraphy remained the diagnostic modality of choice showing moderate to marked increase in radiopharmaceutical uptake in the palmar/ plantar condyles. MRI, CT and PET, whilst excellent for further quantifying the diagnosis were difficult to achieve from the perspective of costs and gaining owner compliance.

Treatment: Initially the horses were spelled for as long as the client permitted or was able to allow, typically 3-4 months. In the veterinarians’ opinion this resulted in the best outcomes. However, oftentimes horses may only get 5-6 weeks due to the racing calendar and trainer/ owner expectations.

Arthramid® Vet was administered bilateral/quadruple to the metacarpo/ tarso phalangeal joint on resumption of training at a dose rate of 2ml (50mg) per joint.

Management Post Treatment: The horses were given 2 to 4 days rest followed by 2 to 3 weeks of ‘easy’ exercise– walking or swimming. The best outcomes seemed to be achieved when they were not galloped for at least 2 to 3 weeks after treatment with Arthramid Vet.

Outcome: Anecdotally this form of treatment has resulted in excellent outcomes for this practice, as measured by a return to previous performance and owner/ trainer satisfaction. The practice has also seen a reduction in the use of corticosteroids, and incidentally a decrease in post galloping EIPH.

The treating veterinarian also reported a subjective improvement in synovial fluid viscosity seen in horses that have been re-treated over multiple preparations and tends to now treat the joints as early as possible in the disease process rather than waiting until the joint is more severely inflamed.

Discussion: Improved outcomes with the use of Arthramid Vet are possibly two-fold. Firstly, due to its augmentation effects on the synovium and capsule, and secondly the subsequent reduction in synovitis as a result.

It is known that with chronic, repetitive injury or chronic inflammation, the synovial intima can become modified and the subintima fibrotic. The joint capsule will heal by granulation tissue formation and may become fibrotic in an unpredictable fashion, therefore changing the joint mechanics. A classic example of this is the dorsal aspect of the fetlock joint where the synovial membrane and joint capsule become oedematous and fibroplastic with associated articular cartilage damage in that area (3). Arthramid Vet’s ability to augment the capsule and improve its load transfer capacity may as a result lessen the impact of shear forces on the subchondral bone plate itself.

Secondly, the significance of synovitis in the pathogenesis of equine OA is now well recognised. The degradative processes of equine OA do not only affect the articular cartilage but also involve the entire joint, including the sub-chondral bone, ligaments, capsule, synovial membrane, and periarticular tissues. Arthramid Vet’s ability to reduce synovitis and improve the nature of the joint fluid may therefore further aid in a reduction in the reoccurrence of clinical signs associated with secondary OA associated with sub-chondral bone disease.

1. Kawkak, CE. Pathologic manifestations of joint disease. In: McIlwraith C, Frisbie D, Kawcak C, van Weeren P, editors. Joint Disease in the Horse, 2nd edn. St Louis, Elsevier; 2016, P49-56
2. Kawcak CE, McIlwraith CW, Norrdin RW, et al. The role of subchondral bone in joint disease: a review. Equine Vet J. 2001;33(2):120–126.
3. McIlWraith C. Traumatic arthritis and posttraumatic arthritis in the horse. In: McIlwraith C, Frisbie D, Kawcak C, van Weeren P, editors. Joint Disease in the Horse, 2nd edn. St Louis, Elsevier; 2016, p. 33-48.

Equine veterinarians have a range of options to treat lameness in horses caused by osteoarthritis (OA) and practitioners use all means at their disposal to ensure horses are exposed to the absolute least amount of discomfort and pain, and potential for injury, while under their care.

Intra-articular (IA) corticosteroid administration is one of the most commonly used treatments, employed principally for their immediate and powerful anti-inflammatory effect. However, these, and non-steroidal anti-inflammatory drugs (NSAID’s), treat the symptoms and provide temporary pain relief without addressing the underlying cause of the painful and debilitating condition.  

Arthramid Vet is now registered for veterinary use. It was introduced to veterinarians in New Zealand (2019) and Australia (2020). A unique, patented product, Arthramid® Vet, that is not a pharmaceutical and has a completely different mechanism of action to conventional treatments. Arthramid® Vet is an inert and biocompatible hydrogel consisting of 2.5% polyacrylamide and 97.5% sterile water. The 2.5% PAAG gel, a porous biomaterial for intra-articular injection, is neuro-innocuous, safe and stable with great tissue integration in joints from various species, including horses. Its 3D network of cross-linked polyacrylamide polymers forms a “scaffold” inside the joint working to improve the joint capsule elasticity lost during the osteoarthritic process.

According to Dr Jason Lowe BVSc., managing director at Innovative Medical Solutions, “the 2.5% PAAG gel integrates into the joint and produces synovial hyperplasia, forming a thick, cushion-like membrane that increases the elasticity and tensile strength of the joint, reducing the pain and inflammation of synovitis and restoring long-lasting joint function.”

Research suggests 2.5% PAAG is more effective in treating OA than conventional treatments and its adoption by veterinarians will allow a progressive reduction in the use of corticosteroids, such as triamcinolone, and other anti-inflammatories in horse racing and other competitive horse sports.

This evidence is supported by multiple clinical trials; Tnibar et al. (2014) directly compared the efficacy of 2mls of 2.5% PAAG with 12mg of triamcinolone acetonide (TA) and 20mg of hyaluronic acid (HA), when injected into a metacarpal / metatarsophalangeal (fetlock) joint, in 40 warmblood horses used for dressage, show jumping or eventing. Twenty horses were assigned into 1 of 2 treatment groups after clinical examination, intra-articular anaesthesia, radiological and MRI assessment, and were clinically evaluated at 1, 3 and 6-months post-treatment. The proportion of lame-free horses were 55%, 65%, and 75% respectively in the 2.5% PAAG treated group and 15%, 40%, and 35% in the control (TA-HA) group. The study concluded that horses treated with 2.5% PAAG were significantly less lame (p<0.001) than those receiving positive control treatment (TA-HA).

Lowe and de Clifford, (pending publication), conducted a prospective double-blinded positive-control study to investigate the efficacy of a 2.5% polyacrylamide hydrogel (Arthramid® Vet) in the management of inter-carpal joint lameness in thoroughbreds. Thirty-three flat-racing thoroughbreds in full training at a single training facility with lameness (AAEP 1-3/5) localised to the inter-carpal joint by intra-articular anaesthesia and radiological assessment were enrolled. Horses were randomly allocated to be treated intra-articularly with either 2mls of 2.5% PAAG, 12mg of triamcinolone acetonide or 20mg of sodium hyaluronate (followed by two further intravenous treatments of 40mg, at weekly intervals), by a treating veterinarian blinded to the examinations at enrolment. All horses were rested for 48 hours’ post-treatment before re-entering an unaltered training regime. Compared to the horses that received triamcinolone acetonide or sodium hyaluronate, horses treated with 2.5% PAAG showed a higher probability of resolution of lameness, joint effusion and reaction to flexion at 4 (P<0.05) and 6 (p<0.05) weeks, with no difference seen between groups at two weeks. There was no significant difference between the triamcinolone acetonide and sodium hyaluronate groups at any time point. Of the horses treated with the 2.5% polyacrylamide hydrogel, 8/12 (67%) were lame free at 12 weeks. This report concluded that 2.5% PAAG could be used in the management of joint lameness in racing thoroughbreds and is superior to and longer lasting than both triamcinolone and hyaluronic acid.

A case study report from three prominent equine practices in the UK using 2.5% PAAG in 341 mainly in-work thoroughbreds (804 various joints) indicated that in 88.9% of cases when no concurrent medication was used, the anticipated outcome of 2.5% PAAG was achieved within 2 months of the initial treatment. Of the 341 horses treated with 2.5% PAAG, 210 horses (61.6%) were known to still be in work after more than 2 years in most cases from the date of initial treatment.

New technologies now give us the means to improve the safety and well-being of our equine athletes and to reduce the potential for injury – all it takes is knowledge and a change in mindset – a sentiment agreed with by Dr Florent David, an equine specialist in Surgery, Sports Medicine & Rehabilitation, and Diagnostic Imaging, who says “Veterinarians and horse owners need to keep in mind the delayed response to PAAG treatment. This delay is normal, but it’s not what clients are accustomed to with joint treatment. PAAG’s take three to four weeks, and sometimes up to six weeks, to take effect. They are not anti-inflammatory drugs or painkillers and, as a result, it requires a different mindset of the trainer and owner expectations, compared to traditional therapies”. He says, “There is mounting evidence that these new products (PAAG’s) are a game changer in the management of joint pain in osteoarthritis, and I’m very glad we have those products available”.

A case series report following the treatment with 2.5% polyacrylamide hydrogel of 804 joints in 341 horses (average of 2.36 joints per horse). The treatments were carried out by three different vets, each at a different practice. The practices were chosen due to the diversity of their equine populations.

Reasons for performing the case series: Intra-articular administration of a 2.5% polyacrylamide hydrogel (2.5% PAAG) has been widely used to treat non-septic arthritis since its introduction to the United Kingdom animal health market, 7 years ago. In order to support an application for Marketing Authorisation (MA), further information, particularly on the safety of the product has been sought from veterinary practices in the United Kingdom.

Objectives: To retrospectively analyse data from horses treated with 2.5% PAAG from three specialist equine practices in the United Kingdom.

Study design: Retrospective case series.

Methods: Horses showing clinical signs of non-septic arthritis were treated intra-articularly with 0.4ml-4mls (dose dependant on joint/s affected) of 2.5% PAAG, by a treating veterinarian. The tarsometatarsal (“TMT”) joint, distal intertarsal (“DIT”) joint, fetlock joint and distal interphalangeal (“DIP”) joint accounted for 89.7% of all joints treated. Ancillary treatments commonly included anti-inflammatory and/or hyaluronic acid preparations and less commonly digital neurectomy.

Results: A total of 341 horses, comprising 804 joints were available for analysis. The veterinary practices involved were all specialist equine centres, whose patients were principally racing thoroughbreds.  70/80 (87.5%) and 232/261 (88.9%) of those treated with 2.5% PAAG and ancillary treatment, and those treated with 2.5% PAAG alone respectively, achieved the anticipated outcome within two months. 15.8% (15/341) received additional injections of 2.5% PAAG, after the initial treatment and 61.6% of horses (210/341) were still in full exercise at least two years after the initial 2.5% PAAG treatment.   Adverse reactions were extremely rare, occurring in only 0.59% of horses (2/341), and both of which responded to conservative therapy.

Limitations: Case selection bias, lack of controls, no blinded assessment. Pending publication.

Conclusion: This case series shows that 2.5% PAAG is safe and effective at alleviating the clinical signs of non-septic arthritis. There appears to be no major benefit or deleterious effect derived from ancillary treatments. Efficacy results appear consistent with those from previously published studies.

This series is also presented as a video webinar covering the outcomes of those treatments in different joint types, the volumes injected, timing of treatment, repeat injections and any adverse reactions reported. https://nupsala-learning.co.uk/the-use-of-polyacrylamide-hydrogel-in-equine-patients-a-case-series-report-3-vets-in-3-practices/