10 Mar 2025
Image: Zoetis
Q: Could you explain the mechanisms behind OA pain and why nerve growth factor (NGF) is a key target for treatment?
Prof Innes: Over the past two decades, research has shown that NGF is a major mediator of joint pain. When a joint undergoes biomechanical stress, molecules from the extracellular matrix stimulate immune cells, leading to the production of cytokines but also NGF. NGF then binds to nociceptors, particularly the TrkA (Tropomyosin Receptor Kinase A) receptor, inducing both peripheral and central sensitisation—essentially amplifying pain signals. So NGF is a key mediator of joint pain as we now understand it.
Q: How does NGF relate to inflammation in OA and how important is this?
Prof Innes: NGF plays a dual role – it not only contributes to pain but also stimulates immune cells to release further inflammatory cytokines, creating a positive feedback loop. Both pain and inflammation are important, but pain relief is often the most immediate concern as it’s the pain which bothers the patient, and which bothers the owner as well.
Q: OA is traditionally associated with older pets, but recent research suggests a high prevalence in younger dogs. Can you tell us more about that?
Prof Lascelles: Yes, and I need to credit John here because for years he’s spoken to me about the fact that osteoarthritis in dogs is driven primarily by developmental disease and of course this abnormal joint development occurs in young animals. Our recent study1 examined dogs between eight months and four years of age and found that approximately 40% had radiographic evidence of OA. Around 16% exhibited moderate or greater pain, while 25% had mild or greater pain, so really surprising figures.
Q: The study also found that many owners weren’t recognising these signs, why do you think that is?
Prof Lascelles: When pain is first present, dogs will initially try to adapt to that, such as bunny hopping. In this study1 looking specifically at young dogs, we found that many owners weren’t identifying the adaptations that their dogs were making. I would also say as veterinary professionals, we aren’t identifying these adaptations that result from pain; we are still focused on signs indicative of activities not being able to be performed. We need that mindset change, to think about how these particular individuals may present and think about the adaptations these dogs are instigating to try and cope with the pain.
Q: Are you comfortable using mAbs in younger OA patients*, considering they may require longer treatment periods?
Prof Lascelles: I am, but I also believe we need to shift our approach to pain management. Instead of short-term interventions when pain is severe, sustained pain relief allows pets to remain active, which supports weight management and muscle strength. These considerations are interlinked; continuous provision of pain relief allows these dogs to further improve. If we have a multimodal approach, it may be that we don’t need lifelong therapy with every aspect of that, but that we can start to back off some of those therapies, potentially some of the drug therapies. I don’t want this to be a confusing message, we need prolonged administration to get these animals back to where they should be; that doesn’t necessarily mean lifelong, but it does mean we need to be regularly reassessing these animals for their need for everything we are providing and whether we need anything additional. So, yes, I’m very comfortable using mAbs in younger* OA patients, but that does not necessarily mean I’m committing to lifelong continuous therapy with them.
Q: Following on from the importance of sustained pain relief, how have Librela and Solensia aided with this?
Prof Innes: These new medications have given us new things to consider, I think compliance is a really important aspect here as I believe this is one of the issues with daily medication at home. We know from studies looking at compliance with daily medications across different chronic diseases that it can be a problem. If we are going to be looking at sustained analgesia, an injectable which lasts for a month is a great way to drive and ensure compliance.
Prof Lascelles: I contributed to a real world study2 which looked at the impact of the introduction of Librela into first opinion practice. The first thing to note is that compliance was high, so 85% of cases received their repeat monthly injections which meant those dogs getting consistent pain control, optimising the degree of improvement which can be seen.
The study also showed that the complexity of the treatment reduced – so fewer medications were needed when Librela was introduced. Decreasing the need for add-on medications also helps with compliance.
Q: Could you share insights from your recent comparative study evaluating Librela against meloxicam3?
Prof Innes: We conducted a randomised parallel-group clinical trial involving 101 dogs recruited from general practice. The dogs were assigned to either the Librela or meloxicam treatment groups, and efficacy was assessed using the Canine Orthopedic Index, a validated client-reported outcome measure.
Q: What were the key findings of the study?
Prof Innes: Both treatments demonstrated efficacy in managing OA pain, but at every time point measured, Librela showed a slightly greater reduction in pain scores compared to meloxicam, although the difference did not reach statistical significance. When examining safety however, there were differences between the two groups. Dogs treated with meloxicam experienced 17 adverse events (AE), including nine cases of gastrointestinal disorders such as vomiting and diarrhoea, as well as three neurological adverse events. In contrast, three AE’s were reported in the Librela group.
Q: Some discussions online have raised concerns about the safety of mAbs. How should vets approach this?
Prof Lascelles: I think all of us can be affected by social media in both positive and negative directions, so when I see posts like this, they do grab my attention and do make me think. However, it’s very easy on social media to blow things out of proportion so, for a particular AE that may be associated with a therapy, we need to consider: how common is it? What type of patient does the AE appear to occur in? Is the AE really associated with the therapeutic, or a result of the patients we, as clinicians, choose to treat? What is the risk versus the benefit, in terms of improved quality of life and control of pain? It isn’t about dismissing AE’s, rather putting things in perspective, and understanding all aspects. Social media can very rapidly and effectively distort the truth. This is why the pharmacovigilance process is very important in educating us in terms of the types of AE’s possible and how commonly they occur.
Q: We have now had Librela and Solensia available to use in our OA patients since 2021, how do you see these fitting into our OA management?
Prof Lascelles: I was involved in some of the early clinical trials with the mAbs and what struck me was the efficacy was obvious, I knew we had a potentially very valuable tool coming down the line. That’s what we now have, another tool in the toolbox, another first line option for managing OA pain.
Prof Innes: I did my PhD in the 1990s and I remember the excitement of the human rheumatologists about the first mAb medicine, for rheumatoid arthritis. But I also remember the shock of the cost/treatment, so I never thought they would come to veterinary medicine. I think it’s amazing that now we have these to treat OA pain in dogs and cats at a fraction of that cost. That innovation will help millions of dogs and cats with OA, something we couldn’t have dreamt of before.
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