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Effectiveness of Oclacitinib in Controlling Canine Allergic Dermatitis
PAG E 4
A D VA N C E S
EFFECTIVENESS OF OCLACITINIB IN CONTROLLING CANINE ALLERGIC DERMATITIS Background Dermatological problems, such as the pruritic conditions of parasitic infestations and allergic skin diseases, are the second most common reason for dogs to be presented to veterinary practices. Glucocorticoids are commonly used to treat dogs with skin disease, particularly if they are pruritic. These drugs are highly effective, but short-term and chronic adverse effects are common. Acute problems, such as polyuria, polydipsia, polyphagia, inappropriate urination in homes, behavioral changes, and panting, can interfere with the quality of life of the dog and result in decreased owner satisfaction and compliance. Long-term administration of glucocorticoids may result in serious health conditions, including pancreatitis, gastrointestinal ulceration, hyperlipidemia, diabetes mellitus, muscle wasting, and iatrogenic hyperadrenocorticism (pharmacologic) and secondary hypoadrenocorticism. Topical glucocorticoids are not suitable for generalized pruritus. Antihistamines have shown only minimal efficacy in the treatment of canine pruritus. Systemic cyclosporin and topical tacrolimus can effectively control atopic dermatitis, but the delayed onset of action makes them impractical as sole therapy for the rapid management of pruritus. Essential fatty acids can improve the skin barrier and help to ameliorate atopic dermatitis but are insufficient to be primary treatment to control acute pruritus. Pruritogenic cytokines are a major stimulus of pruritic behavior in dogs. Oclacitinib selectively inhibits key pathways involved in itch and inflammation associated with allergy. Oclacitinib selectively inhibits Janus kinase 1-dependent cytokines in cellular assays with minimal effects against Janus kinase 2-dependent cytokines involved in hematopoiesis. Janus kinase 1 enzyme activities play a central role in cytokine signaling and are involved in the transduction of many pro-inflammatory, pro-allergic, and pruritogenic cytokines implicated in atopic dermatitis, including interleukin (IL)-2, IL-4, IL-6,
A D VA N C E S
and IL-13. Janus kinases are also involved in the signaling of IL-31, a recently identified cytokine that has been shown to play a key role in canine pruritus. Oclacitinib has been shown to effectively inhibit IL-31 cytokine function in dogs and may significantly reduce pruritus.
Objectives To evaluate the safety and efficacy of oclacitinib for the control of pruritus in dogs associated with allergic dermatitis in a randomized, double-blinded, placebocontrolled trial.
Procedure Owner-assessed severe pruritus and a presumptive diagnosis of allergic dermatitis were determined in 436 dogs. Dogs were randomized to receive either oclacitinib at 0.4 to 0.6 mg/kg orally twice daily or a placebo. An enhanced 10-cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days.
Results Pretreatment owner and veterinary VAS scores were similar for the 2 treatment groups. Oclacitinib was efficacious within 24 hours. Mean oclacitinib owner-assessed pruritus VAS scores were significantly better than placebo scores on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib veterinarianassessed dermatitis VAS scores were also significantly better than placebo scores. Diarrhea and vomiting were reported with similar frequency in both groups.
Author Conclusion Oclacitinib provides rapid, effective, and safe control of pruritus associated with allergic dermatitis.
Inclusions Five figures, 4 tables, 33 references.
Editor Annotation Pruritus is one of the most common reasons for dog owners to seek help from veterinarians. While corticosteroids are generally effective in decreasing pruritus, their adverse effects are sometimes as
troublesome to owners as is the pruritus. Adverse effects include polyuria and polydipsia, increased susceptibility to urinary tract infections, steroid-induced hepatopathy, panting, polyphagia, poor hair growth, thinning of the skin, and other signs of iatrogenic Cushing’s disease. Cyclosporine has proven useful in decreasing pruritus in many dogs with atopic dermatitis. However, gastrointestinal adverse effects (e.g., nausea and vomiting) are common, and improvement may not be evident until the pet has been treated for several weeks. Oclacitanib is a new therapeutic option that has a very rapid onset of action. Significant decreases in pruritus within 24 hours occurred in 44% of the dogs in this study, and 86% had significant improvements by the 7th day of treatment. The incidence of adverse effects in this study was very low and similar between treatment and placebo groups. While longer term studies will be needed to further assess safety, oclacitinib appears to have fewer adverse effects than corticosteroids or cyclosporine. This was a field trial that involved 436 client-owned animals. The findings of this study are very encouraging in that a new alternative to corticosteroids has been found that provides fast and effective control of pruritus. (KLC) Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol 2013;24:479-487.
PAG E 5
A D VA N C E S
EFFECTIVENESS OF OCLACITINIB IN CONTROLLING CANINE ALLERGIC DERMATITIS Background Dermatological problems, such as the pruritic conditions of parasitic infestations and allergic skin diseases, are the second most common reason for dogs to be presented to veterinary practices. Glucocorticoids are commonly used to treat dogs with skin disease, particularly if they are pruritic. These drugs are highly effective, but short-term and chronic adverse effects are common. Acute problems, such as polyuria, polydipsia, polyphagia, inappropriate urination in homes, behavioral changes, and panting, can interfere with the quality of life of the dog and result in decreased owner satisfaction and compliance. Long-term administration of glucocorticoids may result in serious health conditions, including pancreatitis, gastrointestinal ulceration, hyperlipidemia, diabetes mellitus, muscle wasting, and iatrogenic hyperadrenocorticism (pharmacologic) and secondary hypoadrenocorticism. Topical glucocorticoids are not suitable for generalized pruritus. Antihistamines have shown only minimal efficacy in the treatment of canine pruritus. Systemic cyclosporin and topical tacrolimus can effectively control atopic dermatitis, but the delayed onset of action makes them impractical as sole therapy for the rapid management of pruritus. Essential fatty acids can improve the skin barrier and help to ameliorate atopic dermatitis but are insufficient to be primary treatment to control acute pruritus. Pruritogenic cytokines are a major stimulus of pruritic behavior in dogs. Oclacitinib selectively inhibits key pathways involved in itch and inflammation associated with allergy. Oclacitinib selectively inhibits Janus kinase 1-dependent cytokines in cellular assays with minimal effects against Janus kinase 2-dependent cytokines involved in hematopoiesis. Janus kinase 1 enzyme activities play a central role in cytokine signaling and are involved in the transduction of many pro-inflammatory, pro-allergic, and pruritogenic cytokines implicated in atopic dermatitis, including interleukin (IL)-2, IL-4, IL-6,
A D VA N C E S
and IL-13. Janus kinases are also involved in the signaling of IL-31, a recently identified cytokine that has been shown to play a key role in canine pruritus. Oclacitinib has been shown to effectively inhibit IL-31 cytokine function in dogs and may significantly reduce pruritus.
Objectives To evaluate the safety and efficacy of oclacitinib for the control of pruritus in dogs associated with allergic dermatitis in a randomized, double-blinded, placebocontrolled trial.
Procedure Owner-assessed severe pruritus and a presumptive diagnosis of allergic dermatitis were determined in 436 dogs. Dogs were randomized to receive either oclacitinib at 0.4 to 0.6 mg/kg orally twice daily or a placebo. An enhanced 10-cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days.
Results Pretreatment owner and veterinary VAS scores were similar for the 2 treatment groups. Oclacitinib was efficacious within 24 hours. Mean oclacitinib owner-assessed pruritus VAS scores were significantly better than placebo scores on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib veterinarianassessed dermatitis VAS scores were also significantly better than placebo scores. Diarrhea and vomiting were reported with similar frequency in both groups.
Author Conclusion Oclacitinib provides rapid, effective, and safe control of pruritus associated with allergic dermatitis.
Inclusions Five figures, 4 tables, 33 references.
Editor Annotation Pruritus is one of the most common reasons for dog owners to seek help from veterinarians. While corticosteroids are generally effective in decreasing pruritus, their adverse effects are sometimes as
troublesome to owners as is the pruritus. Adverse effects include polyuria and polydipsia, increased susceptibility to urinary tract infections, steroid-induced hepatopathy, panting, polyphagia, poor hair growth, thinning of the skin, and other signs of iatrogenic Cushing’s disease. Cyclosporine has proven useful in decreasing pruritus in many dogs with atopic dermatitis. However, gastrointestinal adverse effects (e.g., nausea and vomiting) are common, and improvement may not be evident until the pet has been treated for several weeks. Oclacitanib is a new therapeutic option that has a very rapid onset of action. Significant decreases in pruritus within 24 hours occurred in 44% of the dogs in this study, and 86% had significant improvements by the 7th day of treatment. The incidence of adverse effects in this study was very low and similar between treatment and placebo groups. While longer term studies will be needed to further assess safety, oclacitinib appears to have fewer adverse effects than corticosteroids or cyclosporine. This was a field trial that involved 436 client-owned animals. The findings of this study are very encouraging in that a new alternative to corticosteroids has been found that provides fast and effective control of pruritus. (KLC) Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol 2013;24:479-487.
PAG E 5