The anti‐inflammatory effect of topical tofacitinib on immediate and late‐phase cutaneous allergic reactions in dogs: a placebo‐controlled pilot study

Blubaugh, Amanda; Rissi, Daniel R.; Elder, Deborah; Denley, Tara; Eguiluz-Hernandez, Sitka; Banović, Frane

doi:10.1111/vde.12532

Cited by 6 publications

(11 citation statements)

References 11 publications

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“…In mice, topical administration resulted in a reduction in the skin swelling that was not seen in animals treated orally, with a reduction in epidermal hyperplasia, parakeratosis, dermal edema, and inflammatory cells infiltration . In dogs topical oclacitinib and tofatinib reduce dermal cellular infiltrates, especially eosinophils and mast cells . Thus, it was anticipated that topical oclacitinib would have benefits over systemic medication—providing a more potent local action, avoiding systemic side effects, and providing the positive results seen in people .…”

Section: Discussionmentioning

confidence: 99%

“…[52][53][54][55] In dogs topical oclacitinib and tofatinib reduce dermal cellular infiltrates, especially eosinophils and mast cells. 58 Thus, it was anticipated that topical oclacitinib would have benefits over systemic medication-providing a more potent local action, avoiding systemic side effects, and providing the positive results seen in people. 62,63 Furthermore, oclacitinib was chosen over tofacitinib due to its efficacy in treatment of atopic dermatitis in dogs and the liberal in this species.…”

Section: Discussionmentioning

confidence: 99%

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Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca

Oliveira

Williams

Bollmann

et al. 2019

Veterinary Ophthalmology

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Objective To assess the efficacy of 0.1% oclacitinib as a single agent, and in combination with tacrolimus 0.01%, for the control of ophthalmic signs of keratoconjunctivitis sicca (KCS) in dogs. Animals studied Thirty‐two dogs (57 eyes) diagnosed with idiopathic KCS were included. Inclusion criteria were Schirmer Tear Test 1 (STT‐1) values <15 mm/min and concurrent clinical signs such as ocular hyperemia and discharge. Procedures The animals were submitted to a randomized, open‐label, 5‐week study and divided into 3 treatment groups treated with the following ophthalmic solutions: (a) 0.1% oclacitinib, (b) 0.1% oclacitinib +0.01% tacrolimus, and (c) 0.01% tacrolimus. Eye drops were instilled twice daily (12‐hour intervals). At each follow‐up examination, STT‐1, clinical signs, and potential drug side effects were assessed. Results Oclacitinib did not significantly improve STT‐1 values or clinical scores. Tacrolimus alone and in combination with oclacitinib increased mean STT‐1 values by 11.84 ± 5.2 and 12.46 ± 5.3 mm/min, respectively (P = 0.0001). Clinical scores of ocular discharge and hyperemia also improved significantly in both groups receiving treatment with tacrolimus (P < 0.05). However, addition of oclacitinib to tacrolimus provided no additional improvement over tacrolimus alone. Conclusions Topical 0.1% oclacitinib twice daily is not effective in controlling the ocular signs of KCS in dogs. 0.01% tacrolimus increased STT‐1 values significantly and could potentially be used as a treatment for mild‐to‐moderate cases of KCS. Synergism between drugs did not occur, and therefore the use of oclacitinib is not justified in cases of canine KCS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca

Oliveira

Williams

Bollmann

et al. 2019

Veterinary Ophthalmology

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“…The order of injections was randomized using statistical computer software (Prism 8.0; GraphPad Softwares, La Jolla, CA, USA) and the investigator (FB) was blinded during intradermal injection evaluations. The concentrations of the substances were chosen from the established intradermal-induced cutaneous allergic reaction studies in dogs (BARBET and HALLIWELL, 1989;MASON and LLOYD, 1996;DEBOER and COOLEY, 2000;PUCHEU-HASTON et al, 2006;GINEL et al, 2007;BIZIKOVA et al, 2008;BIZIKOVA et al, 2010;TEMIZEL et al, 2011;MURPHY and OLIVRY, 2015;BÄUMER et al, 2017;BLUBAUGH et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

“…Twenty minutes after each injection, the extent and severity of the wheals were assessed by the same investigator (FB) who performed the injections. The global wheal score (GWS) was calculated from all measurements as previously reported (BARBET and HALLIWELL, 1989;MASON and LLOYD, 1996;DEBOER and COOLEY, 2000;PUCHEU-HASTON et al, 2006;GINEL et al, 2007;BIZIKOVA et al, 2008;BIZIKOVA et al, 2010;TEMIZEL et al, 2011;MURPHY and OLIVRY, 2015;BÄUMER et al, 2017;BLUBAUGH et al, 2018): GWS = D × E × F (the average diameter (D) in orthogonal directions was measured in millimeters; with erythema (E) and firmness (F). Six hours following all intradermal injections, the global LPR score (GLS) was determined as follows: GLS = E × I (erythema (E); the degree of skin induration (I)).…”

Section: Methodsmentioning

confidence: 99%

“…Intradermal injections of anticanine IgE antibodies (PUCHEU-HASTON et al, 2006;BIZIKOVA et al, 2010;MURPHY and OLIVRY, 2015;BLUBAUGH et al, 2018), compound 48/80 (MASON and LLOYD, 1996;BÄUMER et al, 2017) and histamine (BARBET and HALLIWELL, 1989;GINEL et al, 2007;BIZIKOVA et al, 2010;BLUBAUGH et al, 2018) induce allergic cutaneous reactions in healthy dogs and are used as a screening model for studying the anti-inflammatory effect of anti-allergic drugs before entering clinical trials. Furthermore, the inhibition of the wheal and flare response to histamine and anticanine IgE is a traditional pharmacodynamic tool to measure the immunomodulatory drug effect on the intradermal testing in dogs (BIZIKOVA et al, 2008;BIZIKOVA et al, 2010;TEMIZEL et al, 2011;MURPHY and OLIVRY, 2015).…”

Section: Introductionmentioning

confidence: 99%

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The effect of anti-inflammatory and anti-oxidant diet on immediate and late-phase cutaneous allergic reactions in healthy dogs

et al. 2019

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Canine atopic dermatitis (AD) is a highly pruritic and inflammatory skin disease that affects 10-15% of the canine population. The goal of nutritional management for canine AD is to inhibit the inflammatory response, stabilize the skin barrier and support skin and coat health. A new veterinary-exclusive pet food, Hill's Derm Defense (HDD) diet, has been designed for skin and coat health benefits as well as immune modulation in canine AD. This study aimed to evaluate the effect of administrering an oral HDD diet for 6 weeks in suppressing histamine, compound 48/80 and anticanine IgE antibody-induced global wheal scores (GWS) and late phase reactions (LPR) in nine healthy dogs. On days-10 (baseline), 25 and 46 (3 and 6 weeks of only HDD diet treatment) and day 60 (return to baseline), intradermal injections of histamine, anticanine IgE and compound 48/80 were performed on the right lateral side of the thorax in all the dogs. None of the dogs showed any side effects during the study and the HDD diet was well tolerated by all the dogs. There was no significant reduction in histamine, anticanine IgE and compound 48/80 GWS and LPRs with the HDD diet treatment compared to baseline (day-10) and return to baseline (day 60). This research suggests that HDD diet does not exert inhibitory and anti-inflammatory effects on histamine, anticanine IgE-and compound 48/80-mediated skin reactions in healthy dogs. Future studies should assess the clinical efficacy of the HDD diet in controlled clinical trials of dogs with AD.

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Effect of diphenhydramine and cetirizine on immediate and late‐phase cutaneous allergic reactions in healthy dogs: a randomized, double‐blinded crossover study

Banović

Denley

Blubaugh

et al. 2020

Veterinary Dermatology

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BackgroundCurrently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs.Hypothesis/ObjectiveTo determine and compare the effects oral of DPH and cetirizine on the immediate‐ and late‐phase cutaneous allergic reactions in healthy dogs.AnimalsTwelve healthy laboratory beagle dogs.Methods and materialsThe study was designed as a randomized, double‐blinded crossover study in which each dog served as its own control; twice‐daily oral DPH (2.2 mg/kg) or cetirizine (2 mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10 days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10 days after last medication dosage. Global wheal scores (GWS) at 20 min and late‐phase reactions (LPR) at 6 h post‐injection were evaluated by an investigator blinded to the drug and the interventions.ResultsTreatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study.Conclusion and clinical significanceIn conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.

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The anti‐inflammatory effect of topical tofacitinib on immediate and late‐phase cutaneous allergic reactions in dogs: a placebo‐controlled pilot study

Abstract: Our observations suggest that topical tofacitinib exerts an inhibitory effect on activated canine skin-emigrating immune cells; this drug should be investigated further as a topical immunosuppressive drug in dogs.

Cited by 6 publications

References 11 publications

Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca

Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca

The effect of anti-inflammatory and anti-oxidant diet on immediate and late-phase cutaneous allergic reactions in healthy dogs

Effect of diphenhydramine and cetirizine on immediate and late‐phase cutaneous allergic reactions in healthy dogs: a randomized, double‐blinded crossover study

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