Introduction
Treatments in horses due to osteoarthritis traditionally include rest, controlled exercise, corrective shoeing, nutraceuticals (including glucosamine, epiitalis, hyaluronic acid, and PSGAG’s), non-steroidal anti-inflammatory drugs (NSAID’s), and any combination of the above, along with intra-articular medications including with corticosteroids (with or without hyaluronic acid) or biotechnological substances such as stem cells, platelet rich plasma, or autologous conditioned serum (IRAP). 2.5% iPAAG is the most recent addition to this list.
A recent survey of equine practitioners(1) revealed that whilst up to 87.5% of practitioners use at least some non-steroidal intra-articular therapies (NSIAT’s) to treat joint disease, corticosteroids (+/- hyaluronic acid) remain the intra-articular therapeutic of choice.
Although there were some limitations to this study, including that the use of NSIAT’s could no doubt be either higher or lower than the actual use among the practitioners surveyed, there were other findings worthy of note; that experienced practitioners with a higher lameness caseload and those that performed intra- articular injections in more than 10 horses/month were significantly more likely to use NSIAT’s; that 12 out of the 353 practitioners rated iPAAG as their first choice treatment; that the most cited reason why practitioners did not use NSIAT’s was the economic limitations of the client; and that the availability of iPAAG was problematic for practitioners in the USA compared to those in other parts of the world.
NSIAT’s used by practitioners include platelet-rich plasma, autologous conditioned serum, autologous protein solution, cellular therapies, and polyacrylamide hydrogel (iPAAG).
The authors in the survey concluded that whilst practitioners frequently use NSAIT’s, choosing to treat acute joint pathology more than previously reported, practitioners still have questions about the efficacy of these products and ideal treatment protocols in horses. A better understanding of the disease-modifying effects of these products and investigations into best practices for how and when these products should be used was recommended. With this in mind, we wanted to share our experiences and thoughts on how we believe practitioners should consider combining the use of 2.5% iPAAG with corticosteroids (mainly triamcinolone acetonide TA).
Efficacy of TA vs 2.5% PAAG
A recently published prospective double-blinded positive control study(3) directly compared the efficacy of 2.5% polyacrylamide hydrogel (2.5% iPAAG) in the treatment of middle carpal joint lameness in racing Thoroughbreds against treatments of triamcinolone acetonide (TA) or sodium hyaluronate (HA).
A total of 31 flat-racing Thoroughbreds with lameness (grade 1-3/5) localised to the carpus by intra-articular analgesia were selected. Following a radiological assessment of the carpi confirming the absence of fragment/fracture, the horses were randomly assigned for intra-articular treatment with either 2ml of 2.5% iPAAG, 12mg TA or 20mg HA (followed by two further intravenous treatments of 40mg, at weekly intervals in the HA group only), by a treating veterinarian. All horses were rested for 48 hours post-treatment and then re-entered an unaltered training regimen. Subsequent examinations at 2, 4, and 6 weeks were performed by a blinded examining veterinarian for all groups, while horses treated with 2.5% iPAAG were also monitored up to 12 weeks for recurrence of lameness.
Significantly more joints treated with the 2.5% iPAAG were lame free (83%) at 6 weeks compared to TA (27%; p=0.007) and to HA (40%; p= 0.04). There was no significant difference between TA and HA groups at any time. All the joints treated with 2.5% iPAAG that were lame free at 6 weeks (10/12) were still lame-free at 12 weeks. In conclusion, the study showed that treatment with 2.5% iPAAG led to statistically superior results compared to TA or HA in the management of middle carpal joint lameness in flat-racing Thoroughbreds, with therapeutic effects persisting up to 12 weeks.
These results were consistent with another positive control study presented at ECVS in 2014(4) that compared the efficacy of 2.5% iPAAG (Arthramid®) vs a combination of TA/HA treated fetlock joints in 40 horses. Inclusion criteria included intraarticular analgesia, radiology and MRI. Of the 40 horses meeting the inclusion criteria, 20 were assigned to the treatment group, and 20 to the control group. At 1, 3 and 6 months, estimated proportions of sound horses were 55%, 65% and 75%, respectively in the 2.5% iPAAG treated group, and 15%, 40% and 35%, respectively in the TA/HA treated control group. This study concluded that 2.5% iPAAG demonstrated a significant reduction in lameness when compared with horses treated with TA-HA (p=0.001), with no adverse reactions.
It appears from these and other studies, that 2.5% iPAAG is an effective and safe treatment and that it has superior and longer lasting effects than TA. Therefore veterinarians should probably be considering its use as a first line treatment and earlier in the disease process than previously thought.
Concomitant use of TA and 2.5% iPAAG (Arthramid).
There are no studies to date that have assessed if the joint capsule augmentation resulting from administration of 2.5% iPAAG has any potential influence on excretion rates of intra-articular corticosteroids or drug detection times. Although the fact that administration of 2.5% iPAAG also results in the formation of a new and hypercellular synovial membrane and increased angiogenesis(5) means it might be expected to improve clearance rates. To our knowledge, and with thousands of doses of 2.5% iPAAG now administered in racing and performance horses worldwide, no reports of prolonged drug detection times have been recorded.
Regardless, the simultaneous use of corticosteroids with 2.5% iPAAG may appear at first, to be counterintuitive; the 2.5% iPAAG bio-scaffold is ideal for fibroblasts promoting cell migration and vessel infiltration. Conversely, TA has been shown to decrease both cellular proliferation and collagen production by dermal fibroblasts. Whilst to our knowledge this has not been demonstrated in the joint, it is difficult to see why it wouldn’t have the same influence on synovial fibroblasts. The strategy of using 2.5% iPAAG is to promote disease modification, and if we consider the impact of OA on intimal fibroblasts and the decreased action/ capability for these cells to respond to inflammation, this might not be able to be achieved if we are inhibiting the very cells we are trying to encourage. That said, we acknowledge that concurrent use of corticosteroids and 2.5% iPAAG has taken place and, anecdotally at least, clinicians we have talked to believe they achieve similar results to those of using 2.5% iPAAG alone. In a retrospective case series report of 804 joints in 341 horses(6), 70/80 (87.5%) and 232/261 (88.9%) respectively of those treated with 2.5% iPAAG plus ancillary treatment, or with 2.5% iPAAG alone, achieved their anticipated outcome within two months. Although this data has not undergone peer review it does provide some evidence to support this.
Therefore, from a clinical perspective, it seems most logical to recommend using 2.5% iPAAG alone and as early as practical to modify the disease process and restore joint function. Then at a later time (at least 2 weeks) using corticosteroids if or when necessary to manage any ongoing inflammatory process and where the clinician believes a clinical benefit can be achieved given their knowledge of what disease process is going on in the joint at the time. This would have the added advantages of using the likes of TA at least, with normal drug withhold times and reducing the usage of corticosteroids overall. This may even then serve to address some of the ongoing agency and animal welfare concerns of current usage patterns of corticosteroids across performance equine populations.
How are we using 2.5% iPAAG and TA?
We are encouraging clients more and more to use 2.5% iPAAG (Arthramid) as a first choice treatment once a diagnosis of osteoarthritis (including synovitis, capsulitis, meniscal injury and subchondral bone injury) has been confirmed through intraarticular analgesia +/- secondary imaging. Although at first it might appear expensive, owners are increasingly recognising the value of a better long-term reduction in lameness and, the benefits of a decrease in repeated treatments and ongoing drug or supplement intakes.
Clinical studies show that tissue integration and subsequent augmentation of the joint capsule with 2.5% iPAAG takes between 2 and 4 weeks to occur, although a response to treatment can be seen earlier than that in some cases; in our experience animals typically show a gradual reduction in lameness during the first week after treatment and a concurrent reduction in synovitis and reaction to passive flexion. This continues to improve over the ensuing weeks.
By 4 to 6 weeks no further improvement is expected. Re-examination at 4 to 6 weeks is therefore indicated to either administer a second dose – in those that have only partially responded (about 15% of cases) or to reassess the accuracy of our diagnosis. In this respect and due to its long lasting effect, we find it best to treat the animal during periods of reduced exercise demands or earlier in the animals training programme than what we, and our owners, have previously considered normally. This also allows us to pro-actively manage the animal with the client at the start of the competition season, rather than having to be reactive half way through during the higher demands of competition.
In cases with more marked joint inflammation (synovitis/ capsulitis) we also often prescribe NSAID’s (typically Meloxicam) for 3 to 5 days following treatment with the 2.5% iPAAG. In our experience this can give a better clinical response, presumably because it is reducing the inflammatory profile of the joint whilst the 2.5% iPAAG itself is undergoing the tissue integration process.
In extremely severe and/or acute osteoarthritis cases (marked synovitis/ capsulitis) or when competition schedules mean a 2 to 4 week period is not available to allow a response to treatment with the 2.5% iPAAG, we will still administer corticosteroids (TA) for its immediate anti-inflammatory benefits. This can be done concurrently with no adverse effects, however we still prefer to administer 2.5% iPAAG not within 2 weeks of TA administration, so as to avoid any potential interference with the integration process, as described earlier.
Conclusion
Equine veterinarians have a range of options to treat lameness in horses caused by osteoarthritis (OA) and practitioners must 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.
Whilst corticosteroids remain a popular treatment choice, primarily for their potent anti-inflammatory effects and the fact that they are relatively inexpensive and easily accessible, non-steroidal intra-articular drugs (NSIAD’s) are used more by experienced equine practitioners and as a first choice treatment earlier on in the disease process because of their disease modifying potential. Whilst we recognise that different clients may have varying expectations and financial constraints, it is our responsibility as veterinarians to offer all of the alternative treatment options available for a specific disease.
2.5% iPAAG (Arthramid) comes in a ready-to-use pre-filled 1ml syringe making it easily accessible, and it is now approved in Australia, New Zealand and the US for veterinary (and human) use. In our experience, once a horse has been treated with 2.5% iPAAG it is lame less often and requires less repeated treatments with corticosteroids and ongoing and oftentimes expensive drug and supplement intake. From a client outcome perspective this has been a ‘game-changer’ in how we manage joint lameness in our practice and we can only see its use amongst equine veterinarians increasing as knowledge and an understanding of its benefits increases.
