Conventional veterinary medicine has relied upon corticosteroids and antibiotics for years for a variety of conditions in companion pets. Case in point, corticosteroids are prescribed for canine atopic dermatitis in companion dogs, chronic pancreatitis in cats, osteoarthritis, gastroenteropathies (inflammatory bowel diseases) … and the list goes on. Antibiotics, as well, are prescribed for gastroenteropathies, prophylactically for suspected bacterial infections, or in case of a secondary microbial infection, due to another infectious agent, be it bacterial, viral, fungal, or parasite.
These two “multipurpose” drug therapies have caused systemic and long-term side effects in animals and humans alike. Corticosteroids can induce Cushing’s syndrome, diabetes, liver damage, adrenal gland insufficiency, and gastrointestinal distress to name a few. Overly prescribed antibiotics have led to antibiotic-resistant bacteria and gastrointestinal dysbiosis. Each year new information appears to be released about the consequences of these combined drug therapies.
Nowadays, preventative medicine, vitamin and minerals, and more gentler therapies couched in purview of holistic medicine are being used more frequently. Additionally, several monoclonal antibody therapies (MAT) have been approved and introduced in recent years for humans and animals.
Clonal antibody therapies are rapidly developing and improving. Notice, we left off “mono”, because polyclonal antibody therapies have been around for decades. Here’s an example: convalescent plasma transfusions against infections like canine parvovirus or COVID-19 in people are polyclonal antibody therapies.
A broad generalization of monoclonal antibody technology is that it identifies the source of the problem, and then finds the one specific antibody that targets the problem either directly or indirectly. An example of an indirectly targeted antibody is usually blocking something that feeds the problem. In essence, these substitute antibodies restore, enhance, block, bind, modify or mimic the immune system’s attack on unwanted cells in a very specific manner. So, please view MAT as “next generation” rather than “brand new”.
A major benefit of injectable MAT is that they are not metabolized by the kidneys and liver unlike several oral medications.
But, an Exception is in One Cancer Monoclonal Antibody Therapy…
We found one exception in human medicine. However, it is not because of the metabolization, but because of the block it creates.
We all have vascular endothelial growth factors (VEGF) and need them. However, some cancer cells make too much VEGF. Bevacizumab (Avastin) blocks VEGF to starve cancerous tumors. Blocking VEGF may prevent the growth of new blood vessels, including normal blood vessels and blood vessels that feed tumors. In turn, it can cause side effects such as high blood pressure, bleeding, poor wound healing, blood clots, and kidney damage.
Kidney damage does not appear to be a side effect of gilvetmab by Merck, which is a USDA conditionally approved MAT for companion dogs with either mast cell tumor (stage I, II or III) or melanomas (stage II or III).
The MAT does not target the cancers specifically, rather it prevents the cancer from turning off the immune system. Gilvetmab is a checkpoint inhibitor that works by blocking PD-1 on the T cell from interacting with programmed cell death ligand 1 (PD-L1) on the cancer. This allows T cells to regain their ability to kill cancer cells.
In the initial trial of 26 client-owned dogs with mast cell tumor, 73% experienced a decrease in target lesion size or maintained stable disease. In the initial trial of 25 client-owned dogs with melanoma, 60% experienced a decrease in target lesion size or maintained stable disease.
Reported adverse events were generally transient, mainly including lethargy, inappetence or gastrointestinal upset.
Infectious Diseases
Are there other risks with monoclonal antibodies? Of course; everything comes with a risk. However, there appears to be hypervigilance regarding the risks and the potential risks of new therapies these days. For instance, it is difficult to keep up with the approved and no-longer-approved monoclonal antibody treatments against COVID-19, because the virus continuously mutates and can escape the therapeutic benefits of MAT.
For dogs, Elanco recently received conditional approval from the U.S. Department of Agriculture (USDA) for a MAT called CPMA against canine parvovirus (CPV). CPMA binds to CPV to neutralize it before it enters the cell.
A field safety study of 147 client-owned dogs of various breeds ranging in age from six weeks to 15 years concluded that the product is well tolerated when intravenously administered to healthy (uninfected) dogs. The most common adverse reactions reported were injection site reactions in 4% of the dogs. Two dogs under the age of eight weeks did pass away, but necropsy by the respective study investigator deemed the deaths unlikely to be related to the therapy.
It is unknown at this time whether CPMA therapy will interfere with the vaccine response.
The First Monoclonal Antibody Therapy for Companion Pets
The first monoclonal antibody ever to be approved by the USDA was Cytopoint for canine atopic dermatitis. Cytopoint directly targets, binds, and neutralizes the cytokine, canine IL-31, which is associated with chronic itching.
Osteoarthritis
Are you wondering why these monoclonal antibodies for companion dogs are approved by the USDA and not the Food and Drug Administration (FDA)? For years, vaccines (biologics) were assigned to and approved by the USDA and all other therapies for companion animals were assessed and approved by the FDA. To add further confusion, the FDA recently approved feline and canine MAT to combat osteoarthritis (OA) pain.
Both the canine and feline OA MAT bind to nerve growth factors (NGF) before they can bind to pain sensors. People, cats and dogs with OA and certain other conditions have an overabundance of NGF.
The breakthrough is in the development of these MAT that recognize that cats are not dogs and that dogs are not humans. Indeed, canine and feline NGF are similar to the NGF in other species, such as human and mice. MAT from one species often can induce an immune response when used without modification in another species. However, for therapeutic purposes, antibodies need to be species-specific to reduce the risk of adverse immunoreactions to the antibody.
In a 3-month study, 77% of companion cat parents reported improvement in signs of pain when their cats were injected monthly with Solensia (frunevetmab). However, 67% of parents stated they saw improvement in signs of their cat’s pain in the placebo group. This made us wonder if there was a placebo effect. For example, did companion cat parents’ awareness to OA make them modify food intake to reduce weight or add another facet of the multi-modal approach to OA?
We decided to focus our review on the activity levels that were electronically monitored. Interestingly, across the entire 8-week data collection period post-treatment, the Solensia-treated group showed little overall change from baseline (mean decrease 0.9%) while the placebo-treated group showed a mean of 9.3% decrease in weekly activity. The researchers hypothesized that this could be due to a falsely elevated baseline because the cats were not accustomed to the new collars.
Possible side effects of Solensia included vomiting, diarrhea, injection site pain, scabbing on the head and neck, dermatitis and pruritus (itchy skin). It was determined that these effects were relatively mild and did not require cessation of treatment.
Please remember that cats especially are prone to chronic kidney failure. Solensia should not affect the kidneys as can occur with non-steroidal anti-inflammatory drugs. So, Solensia may be the better or first option for conventional veterinary therapy added to a multi-modal approach to decrease the symptoms of OA.
The results for giving Librela (bedinvetmab) to companion dogs also have been studied. Improvements in pain score were shown in 43.5% of dogs treated with Librela compared with 16.9% in dogs given placebo according to European field studies. However, the examinations by veterinarians also showed significant improvements in the Librela-treated group compared to the placebo group.
However, the US field studies were less effective. Treatment success was achieved in 47.4% of Librela-treated dogs compared with 36.6% of dogs given placebo.
At Hemopet, we prefer OA preventative measures such as supervised activity and weight control. Of course, OA is a degenerative disease that typically will worsen overtime. When that occurs, a multi-modal approach is preferred. Talk to your veterinarian if Solensia for cats or Librela for dogs will be a useful drug for your companion pet and how it can fit in with the multi-modal approach.
Long-Term Side Effects
We do not know the long-term side effects of MAT. However, side effects beyond injection site reactions will more than likely be MAT-specific like those of Avastin.
Additional References
Chakraborty, Chiranjib et al. “A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations.” Frontiers in immunology vol. 13 801522. 9 Feb. 2022, doi:10.3389/fimmu.2022.801522, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863680/.
Enomoto, Masataka et al. “Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats.” The Veterinary record vol. 184,1 (2019): 23. doi:10.1136/vr.104590, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326241/.
Pelletier, J. Peter R., and Faisal Mukhtar. “Passive Monoclonal and Polyclonal Antibody Therapies.” Immunologic Concepts in Transfusion Medicine (2020): 251–348. doi:10.1016/B978-0-323-67509-3.00016-0, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153350/.
Senefeld, Jonathon W et al. “Convalescent plasma to deliver therapeutic antibodies against COVID-19.” Trends in molecular medicine vol. 28,5 (2022): 435-436. doi:10.1016/j.molmed.2022.02.005, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858694/.
Struble, Evi B et al. “Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies.” Pharmaceutics vol. 15,5 1538. 19 May. 2023, doi:10.3390/pharmaceutics15051538, https://www.mdpi.com/1999-4923/15/5/1538.
Tobian, Aaron A R et al. “COVID-19 convalescent plasma.” Blood vol. 140,3 (2022): 196-207. doi:10.1182/blood.2021012248, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548835/.
Yewdell, Jonathan W. “Antigenic drift: Understanding COVID-19.” Immunity vol. 54,12 (2021): 2681-2687. doi:10.1016/j.immuni.2021.11.016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669911/.