A randomised controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis

被引:13
作者
Olivry, Thierry [1 ]
Lokianskiene, Viktorija [2 ]
Blanco, Alejandro [3 ]
Del Mestre, Pablo [4 ]
Bergvall, Kerstin [5 ]
Beco, Luc [6 ]
机构
[1] NC State Univ, Coll Vet Med, Dept Clin Sci, 1060 William Moore Dr, Raleigh, NC 27607 USA
[2] VetPet LT, Jonava, Lithuania
[3] Clin Dermatol, San Antonio De Padua, Buenos Aires, Argentina
[4] Consultorio Dermatol Vet, Mar Del Plata, Argentina
[5] Swedish Univ Agr Sci, Fac Vet Med & Anim Husb, Uppsala, Sweden
[6] Cabinet Vet, Spa, Belgium
关键词
JANUS KINASE INHIBITOR; CLIENT-OWNED DOGS; SEVERITY SCALE; APOQUEL(R); EFFICACY; VALIDATION; PRURITUS; SAFETY;
D O I
10.1111/vde.13134
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD). Objectives To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration. Animals Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus. Materials and Methods Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14. Results On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving. Conclusions and Clinical Relevance The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects.
引用
收藏
页码:99 / 106
页数:10
相关论文
共 19 条
[1]   Immune regulation by glucocorticoids [J].
Cain, Derek W. ;
Cidlowski, John A. .
NATURE REVIEWS IMMUNOLOGY, 2017, 17 (04) :233-247
[2]   The pharmacokinetics of oclacitinib maleate, a Janus kinase inhibitor, in the dog [J].
Collard, W. T. ;
Hummel, B. D. ;
Fielder, A. F. ;
King, V. L. ;
Boucher, J. F. ;
Mullins, M. A. ;
Malpas, P. B. ;
Stegemann, M. R. .
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 2014, 37 (03) :279-285
[3]   A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis [J].
Cosgrove, Sallie B. ;
Wren, Jody A. ;
Cleaver, Dawn M. ;
Walsh, Kelly F. ;
Follis, Stacey I. ;
King, Vickie I. ;
Tena, Jezaniah-Kira S. ;
Stegemann, Michael R. .
VETERINARY DERMATOLOGY, 2013, 24 (06) :587-+
[4]   Emerging therapies for atopic dermatitis: JAK inhibitors [J].
Cotter, David G. ;
Schairer, David ;
Eichenfield, Lawrence .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2018, 78 (03) :S53-S62
[5]   Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib [J].
Fukuyama, Tomoki ;
Ganchingco, Joy Rachel ;
Baumer, Wolfgang .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2017, 794 :20-26
[6]   Efficacy of oclacitinib (Apoquel®) compared with prednisolone for the control of pruritus and clinical signs associated with allergic dermatitis in client-owned dogs in Australia [J].
Gadeyne, Caroline ;
Little, Peter ;
King, Vickie L. ;
Edwards, Nigel ;
Davis, Kylie ;
Stegemann, Michael R. .
VETERINARY DERMATOLOGY, 2014, 25 (06) :512-U43
[7]   Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy [J].
Gonzales, A. J. ;
Bowman, J. W. ;
Fici, G. J. ;
Zhang, M. ;
Mann, D. W. ;
Mitton-Fry, M. .
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 2014, 37 (04) :317-324
[8]   Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification [J].
Hensel, Patrick ;
Santoro, Domenico ;
Favrot, Claude ;
Hill, Peter ;
Griffin, Craig .
BMC VETERINARY RESEARCH, 2015, 11
[9]   Development and validation of a graphic 2D investigator's global assessment instrument for grading the overall severity of atopic dermatitis in dogs [J].
High, Endya J. ;
Olivry, Thierry .
VETERINARY DERMATOLOGY, 2020, 31 (03) :207-+
[10]   Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis [J].
Kim, Jung Eun ;
Kim, Jong Sic ;
Cho, Dae Ho ;
Park, Hyun Jeong .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (08)