Ron Hines DVM PhD
This article repeats much of what you will find in another article of mine that concerns the very similar new Zoetis produce for arthritis pain management in cats called Solensia®. You can read that article here . Both are the same anti-nerve growth factor medications. It is just that the cat product Solensia® has been bioengineered (“felinized”) to work in cats and Zoetis’ canine product, Librela®, has been bioengineered (“caninized”) to work in dogs.
In April of 2021, the European Medical Agency granted Zoetis permission to market their new pain-reliving product, a monoclonal antibody (mAb), bedinvetmab (Librela®) in the European Union. A month later the Canadian NRPRA did as well.
Librela® is a new treatment designed to reduce pain in dogs that suffer from arthritis. The drug is an injection that your veterinarian gives just below your dog’s skin once a month. Librela® is designed to seek out and destroy a specific protein that all dogs manufacture. That protein is called nerve growth factor or NGF . The canine form of this drug was developed in Ireland by a company, Nexvet, which was subsequently purchased by Pfizer. That was just before Pfizer spun off its veterinary drug subsidiary as Zoetis. To obtain permission to market Librela® in Europe, Zoetis provided the Agency with dog-owner opinions of the drug’s effect 28 days after their dog’s injection. The Company’s results indicated that 43.5% of the owners of dogs that received Librela® thought their dog’s ability to get about had improved; while only 16.9% of the owners of dogs that received a placebo injection thought that their dog’s ability to move about had improved. A second study was done in the United States. In that one, 135 dogs with mild to moderate arthritis received a Librela® injection while 137 dogs received a placebo injection. The EMA website does not indicate how that turned out. They do mention that a small number of the treated dogs experienced swelling and tenderness at the site of the injection. I mentioned that a few month after the European approval, Zoetis obtained authorization to market Librela® in Canada as well. However, to the best of my knowledge, as of May 2022, the FDA has not yet approved the sale of Librela® in the United States or even mentioned that Zoetis has applied for that approval.
However, in March of 2020, the FDA did agree to consider Pfizer’s request to approve tanezumab, the “humanized” form of the same anti-nerve-growth factor (NGF) that is in Zoetis’ Librela® and Solensia®. Tanezumab was offered to the FDA as a non-narcotic option for the treatment of knee and hip arthritis pain in people. However, both the FDA and the EMA refused to approve the human product based on a prior study in which patients that took the drug needed knee and hip replacements sooner than similar patients that did not take it. It is not clear if their joint deterioration was due to a decrease in pain that allowed them to use the joint too vigorously or if the drug itself caused the problem in some other way.
The bar for new animal drug approval is set lower than it is for drugs that are intended for use in humans. Never expressed or insinuated – but perhaps in their minds, “lets give the dog and cat versions a go first and see how that turns out”.
Do Veterinarians Need Better Chronic Pain Control Medications For My Dog Than They Have Now?
Yes we do.
We veterinarians have the same tools today that your physician has to treat arthritic and other chronic pain in you:
Veterinarians can give your dog NSAIDs like carpofen (Rimadyl®), firocoxib (Previcox®), grapiprant (Galliprant®) or meloxicam (Metacam®) to decrease its joint inflammation pain. Most dogs handle those drugs reasonably well. But side effect can occur that include gastrointestinal irritation, vomiting, a drop in appetite and diarrhea. Other than meloxicam (Metacam®) physicians prescribe different but similar NSAIDs to their patients.
We can give your dog corticosteroid injections or corticosteroid pills such as prednisone that are potent blockers of chronic joint inflammation and the pain that produces. However corticosteroids also have side effects that include weight gain, fluid retention, excessive thirst and urination, panting, increased susceptibility to infections, Addison’s disease upon withdrawal, etc.
Some veterinarians dispense narcotics like tramadol for pain, or even fentanyl (Duragesic®) patches when nothing milder is effective anymore. Others hope that gabapentin (Neurontin®) will provide sufficient pain relief for your dog. Fentanyl is probably helpful, but the effectiveness of the last two have never been validated.
There are veterinarians who suggest acupuncture, homeopathic remedies and “alternative medicine” for the control of pain in your dog. But there is really no scientific evidence that any of those things actually work – in pets or humans. ( read here & here ) Other vets suggest therapeutic laser therapy as an alternative to traditional physiotherapy. And still others suggest mood-altering drugs like amitriptyline or imipramine based on their use in treating human fibromyalgia. None of these are likely to do your dog any harm when given under veterinary supervision; but I personally have no faith in any of them. Giving your dog extra time, love and affection and altering its lifestyle to deal with its disabilities is likely to do it considerably more good than mood modifying drugs designed to treat depression.
What Is Nerve Growth Factor (NGF) And How Does It Relate To My Dog’s Arthritis Pain?
Nerve growth factor is a small, protein-like molecule that individual nerve cells (neurons) use to communicate with each other. NGF helps determine which neurons survive and prosper (read here) and has more recently been found to have a host of different functions within the mature body ranging from insulin secretion from the pancreas (read here) to allergic inflammation. (read here) Librela® should cause your dog to have less NGF in its system. That could mean less arthritis pain, but we know very little about what else might occur. In all species the functions of NGF are different during embryonic development and growth than they are in adults.
The nerve highway through which signals travel in you and your dog is a two way street. Some nerve signals travel from the brain to the far ends of its branches throughout the body to tell cells there what to do (motor neurons) . Others travel in the opposite direction, from the fine ends of its branches throughout the body to the brain to communicate cold, warmth, taste, feel, smell, etc. Those are called sensory neurons. The finger-like ends of some sensory neurons appear to only sense pain. (read here)
By 2006, it became known that blocking the effects of NGF blocked pain. (read here) The Pfizer and Lilly drug companies invested $550 million dollars into their research on tanezumab anticipating that a successful human NGF-blocking medications would have a $1.23 billion dollar market. All the drugs that were contemplated were monoclonal antibodies (mAb’s) – protein “smart bombs” carrying “payload” antibodies that seek out and disable in theory only one compound within the body. As I mentioned at the beginning of this article, the Pfizer’s compound, tanezumab, has unresolved issues. But one veterinary mAb that did make it to market several years ago is Zoetis’ Cytopoint® .
What Do Studies Tell Us About The Effectiveness And Safety Profile Of Medications Similar To Librela®?
The basic science behind Librela® appears valid and it would be wonderful if Librela® turns out to be an unqualified successes. But it is impossible to predict that based on the Zoetis-sponsored studies that have been released to the public so far. Lavish drug company publication-funding made it harder and harder for people like me to determine the true worth of medications and procedures across the entire spectrum of veterinary medicine. There is no doubt in my mind that purse string control influences study outcomes. (read here , here & here )
Where Can I Find Unbiased Information Regarding Librela®?
For a start, try the Dog Owner Librela® Feedback Page
If you follow that link, I need to begin with an observation that people whose pets experience unexpected unwanted side effects from a medication tend to report them to me more frequently than those who were satisfied with their pet’s experience using a drug. That has been found to be the case with human drugs as well. You can see that in my webpage that concerns another Zoetis mAb product, Cytopoint®. However the Dog Owner Librela® Feedback Page is a good place to start. Nobody’s thumb is on the scale there.
Other unbiased online sources of information will be harder for you to find. As of March 2022, Wikipedia has no page on bedinvetmab (Librela®) . When they eventually do, it will probably be created by or at the behest of Zoetis. That is quite legitimate. But you won’t find links to this or any of my other articles there.
What About The Dog Owner Surveys That Zoetis Conducted?
Pet Owner opinion has been found to be an unreliable way to measure drug effectiveness. In one of Zoetis’ studies of Solensia®, the sister “felinized” equivalent of “caninized” Librela®, 67% of cat owners whose cats received the placebo injection thought that their cat had improved after its injection too. That wasn’t much less than the number that thought their cat’ pain had lessened after the real injection.
It’s just our human nature to try to maintain a positive attitude and hope for the best. ( read here & here ) Activity monitors, like the one on the 12 year old Labrador cross in the photo above, are really the only valid way to judge the effectiveness of any pain-control medication you give to your dog or cat. (read here)
Other than through the use of activity monitors, veterinarians and dog owners have no accurate way to measure arthritic pain levels in dogs. And even then there are major limits to its accuracy. Just like you, your dog can become reluctant to move for a plethora (=a very large number) of reasons that have nothing to do with its joints. You know your dog best. Go with your instincts.
Joint x-rays are also unreliable indicators of pain. Studies have shown that only ~50% of people over the age of 65 that have x-ray evidence of arthritic knee joint changes experience any knee pain. And those that have joint pain do not necessarily have x-ray evidence of arthritis. As for hip pain, only 9.1 – 15.6% of people that experienced hip pain had any x-ray evidence of hip arthritis. And of those that did have evidence of hip arthritis, only 20% reported frequent hip pain.
Acute pain, such as from a cruciate or elbow ligament tear or a disc injury, can have positives as well as negative effects. Pain decreases motion, and your dog’s reluctance to move and the inactivity that provides gives it’s body a chance to heal.
Older dogs and old cats often have kidney health issues. (read here) That might lead your veterinarian to consider dispensing Librela® to your elderly pet on a risk-to-benefit basis. We do not know how or if lowering your dog’s NGF level affects its kidneys. But there is an interplay. (read here & here)
There are other questions yet to be answered regarding the long-term benefit of Librela® in reliving chronic arthritis pain in dogs. When laboratory rats were given injections of mouse nerve growth factor in an attempt to produce antibodies against NGF similar to what Librela® does, the rats did produce anti-NGF antibodies. However that had deleterious effects throughout their nervous system. (read here) That study was performed long ago. Perhaps it was accurate; perhaps it wasn’t. Perhaps Zoetis keeps its recommended monthly dose low enough to avoid this problem or perhaps dogs do not react in similar ways to rats.
Another unknown is if dogs receiving an mAb such as Librela® after multiple monthly injections learn to recognize that it is foreign to their body and destroy it. If so, will the drug loose its effectiveness over time? There are instances of that occurring with therapeutic mAbs , it is called loss of response or LOR. (read about that here) Hopefully that will not be the case.
Before Your Dog Receives This Product
When Librela® becomes available where you live, Please read the entire label online because there might be more warnings I did not mention and because the label directions may have changed by the time you read this article.
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