Atopic Dermatitis in Dogs

Atopic dermatitis (AD) is a genetically predisposed, inflammatory skin condition caused by hypersensitivity to environmental allergens such as pollen, house dust mites, and mold. Current research suggests that the disease arises from a complex interaction of genetic and environmental factors. Dogs with atopic dermatitis primarily show symptoms such as itching, redness, and chronicChronic refers to a condition or disease that is long-lasting or permanent. Chronic diseases often develop slowly and can lead to persistent or recurring health problems over time. skin changes.

Studies on the treatment of AD are increasingly focusing on influencing the immune systemThe immune system is the body’s defense system against infectious agents such as bacteria, viruses, fungi, and parasites. It comprises a complex network of organs, cells, and molecules that work together to protect the body. and using newer medications such as Janus kinase inhibitors (JAK, or Jakinibs, e.g., oclacitinib, brand name Apoquel) as well as monoclonal antibodies that specifically target itching (e.g., lokivetmab). The active ingredient has been approved in the EU since 2017 and is injected once a month under the skin (subcutaneously).

Genetic Selection through Breeding

As part of research at Uppsala University, genes have been identified in dogs that are important for both the skin barrier and the immune defense. A significant finding is that a specific gene in dogs is a major risk factor for atopic dermatitis. Since the gene can be identified, it opens the way for targeted selectionSelection refers to the process of natural or artificial selection of specific individuals for reproduction, based on desired genetic traits. In breeding, this is applied to promote specific characteristics in dogs and cats. in the parent animals in dog breeding.

Tengvall, K., Sundström, E., Wang, C. et al. Bayesian model and selectionSelection refers to the process of natural or artificial selection of specific individuals for reproduction, based on desired genetic traits. In breeding, this is applied to promote specific characteristics in dogs and cats. signature analyses reveal risk factors for canineCanine refers to anything related to dogs. The term is used to describe characteristics, diseases, or specific aspects that specifically affect dogs. atopic dermatitis. Commun Biol 5, 1348 (2022). https://doi.org/10.1038/s42003-022-04279-8

Drug Therapy

Janus Kinase Inhibitors

Mechanism and use: Janus kinase inhibitors (JAK inhibitors) block specific enzymesEnzymes are biological catalysts that accelerate specific chemical reactions in the body without being consumed. They play a crucial role in virtually all physiological processes. involved in the signaling of cytokines, especially those that control the immune responseAn immune response is the immune system’s reaction to foreign substances (antigens), such as microorganisms or proteins. It involves a series of processes aimed at recognizing, fighting, and eliminating these antigens. and the inflammatory process. In atopic dermatitis, cytokines such as interleukin-2, -4, -6, and -31 play a key role by promoting inflammation and itching. Oclacitinib (brand name: Apoquel) is the most prominent JAK inhibitor currently used in veterinary medicine to treat dogs with atopic dermatitis.

Efficacy and safety: Oclacitinib works quickly and effectively by relieving itching and reducing inflammation within a few hours of administration. This makes it particularly useful in acuteAcute refers to a condition that occurs suddenly and is usually of short duration. In a medical context, it describes symptoms or illnesses that can quickly become serious and require immediate attention. flare-ups. Studies have shown that oclacitinib is well tolerated, even with long-term use. Side effects are relatively rare and include mild GastrointestinalGastrointestinal refers to the gastrointestinal tract, a system that extends from the oral cavity to the anus and is responsible for the digestion of food and the absorption of nutrients. disturbances and, in rare cases, a slight increase in the risk of infectionAn infection is the colonization and multiplication of pathogens such as bacteria, viruses, fungi, or parasites in an organism, which often, but not always, leads to a disease. due to the immunosuppressiveImmunosuppressive agents are medications or substances that specifically suppress the activity of the immune system. They are used in dogs and cats to treat autoimmune diseases, allergies, and to prevent rejection reactions after transplants. effect.

Current research: Research is currently focused on the long-term safety of oclacitinib, specifically regarding the risk of infections and neoplastic diseases with chronicChronic refers to a condition or disease that is long-lasting or permanent. Chronic diseases often develop slowly and can lead to persistent or recurring health problems over time. use. New JAK inhibitors are also being developed that have more specific effects and potentially fewer side effects.

Monoclonal Antibodies

Mechanism and use: Monoclonal antibodies are specifically developed proteins that recognize and neutralize specific molecules in the body. In atopic dermatitis, interleukin-31 (IL-31) is a key factor for itching. Lokivetmab (brand name: Cytopoint) is a monoclonal antibodyAn antibody is a protein produced by the immune system to recognize and bind specific antigens. By binding to the antigen, antibodies can help destroy or neutralize it. that specifically targets IL-31, thereby effectively reducing itching.

Efficacy and safety: Lokivetmab has proven to be highly effective, especially in dogs with severe itching that does not respond adequately to other treatments. It offers a long-lasting effect (up to 4 weeks after a single injection), making it an attractive option for dogs with chronicChronic refers to a condition or disease that is long-lasting or permanent. Chronic diseases often develop slowly and can lead to persistent or recurring health problems over time. AD. The safety of lokivetmab is generally considered high because it specifically targets a single cytokine and therefore has less impact on the general immune systemThe immune system is the body’s defense system against infectious agents such as bacteria, viruses, fungi, and parasites. It comprises a complex network of organs, cells, and molecules that work together to protect the body..

Current research: Current studies are examining the long-term use of lokivetmab and its possible integration into multimodal therapyTherapy refers to the treatment of diseases or disorders with the aim of alleviating symptoms, promoting healing, or improving quality of life. Therapies can be medicinal, surgical, or through other medical interventions. concepts that include a combination of JAK inhibitors, immunotherapies, and local (topicalTopical refers to the direct application of medications or treatments to the skin or mucous membranes for a local effect, without being absorbed into the body.) treatments. It is also being investigated how lokivetmab can be used in earlier stages of the disease to prevent the progressionProgression refers to the advancement or worsening of a disease over time. It describes an increase in the severity or extent of the disease symptoms. of atopic dermatitis.

Comparison and Combination of Therapy Approaches

Combination therapies: An interesting area of current research is the combination of JAK inhibitors and monoclonal antibodies to maximize therapeutic efficacy and minimize side effects. By combining oclacitinib and lokivetmab, better control of symptoms can be achieved, especially in severe AD or in dogs that do not respond adequately to monotherapy.

Individualized therapyTherapy refers to the treatment of diseases or disorders with the aim of alleviating symptoms, promoting healing, or improving quality of life. Therapies can be medicinal, surgical, or through other medical interventions.: The development of these targeted therapies makes it possible to individualize the treatment more. Depending on the severity of the disease, the response to different therapies, and the individual risk profile of the dog, veterinarians can specifically choose between these options or combine them.

Conclusion

The use of Janus kinase inhibitors and monoclonal antibodies represents a significant advance in the treatment of atopic dermatitis in dogs. These targeted therapies offer effective symptom control and have the potential to significantly improve the quality of life of affected dogs. Ongoing research focuses on further optimizing these therapies, ensuring their long-term safety, and developing new, even more specific treatment approaches. As a precaution, regular veterinary monitoring is recommended, as there are currently few long-term studies on the applications.

Sources

Marsella, R.: New Treatments and Validations for Atopic Dermatitis in Humans After Comparative Approach With CanineCanine refers to anything related to dogs. The term is used to describe characteristics, diseases, or specific aspects that specifically affect dogs. Models. In: Recent Advances in the Treatment of Atopic Dermatitis. DOI:10.5772/intechopen.1001478

Bizarro, A., Martins, A., Pinto, M., Fernandes, B., Pereira, H., Braz, B., & Lourenço, A. (2022). Protocolo alternativo com oclacitinib para dermatite atópica canina: Uma solução capaz de reduzir custos. Rev. Port. Imunoalergologia, 30, 31-41.

Ryguła I, Pikiewicz W, Kaminiów K. Novel Janus Kinase Inhibitors in the Treatment of Dermatologic Conditions. Molecules. 2023; 28(24):8064. https://doi.org/10.3390/molecules28248064

Sanchez, M.D., Bensignor, E.: Critically appraised topic: Benefits and risks of oclacitinib in treatment of allergic pruritus in dogs

Revue Vétérinaire Clinique

Volume 59, Issue 2, June 2024, Pages 72-88