ApoquelvsAtopicavsSteroids vsCADIJason Pieper DVM MS DACVD - PDF document

1 1 ApoquelvsAtopicavsSteroids vsCADIJason
1 ApoquelvsAtopicavsSteroids vsCADIJason Pieper, DVM, MS, DACVD Overview of each drugPersonal Clinical Experience Multifactorial, incompletely understood pathogenesis.Genetic alterations of immune systemOutside-Inside-Outside TheoryTEWL, Ceramidesand lipids, FilaggrinSkin microbiota, Staph inflammation, AMP’s 2 Compounded Oclacitinib Selective for JAK1 inhibitorInhibition of cytokinesDose dependent inhibitionJAK2 JAKs activa

2 te the intracellularproteins called Sign
te the intracellularproteins called Signal Transducer and Activator of Transcription (STAT) to induce gene transcription mRNARNA polymeraseof DNAJAK activation(Janus kinase)Cytokine JAK inhibitorJAK STAT STAT dimerization membrane Translationof mRNA Cell function B. Lymphocyte Cytokines D. Cytokine JAK inhibitors workto block the activity in cells where activity is mediated by cytokines that work through JAK. 3 0.4-0.6 mg/

3 kg PO q12h for 2 weeks, then q24h70-90%
kg PO q12h for 2 weeks, then q24h70-90% improvementContraindicatedLess than 12 months of agePrevious neoplasiaBreeding dogsPregnant or lactating dogs Apoquel–Short Term Side Effects Vomiting1.8-4.1% Diarrhea 0.9-3.4%Dermatitis 0.9%Lethargy0.9-1.4%Anorexia 0% Polydipsia0%Elev. Liver enz.2.7%Anemia0.5%New mass2.7% 2.3-4.6%1.4%1.4-2%1.4-2.6%1.4% 1.4% ApoquelLong Term (mean of 401 days) –Clinical Side Effects247 Do

4 gsUTI/Cystitis –11.3%Vomiting –10.1%Otit
gsUTI/Cystitis –11.3%Vomiting –10.1%Otitis –9.3%Pyoderma–9.3%Diarrhea –6.1%Anorexia –2.8% 4 ApoquelLong Term (mean of 401 days) -Confirmed or suspected malignant neoplasia(euthanized) –4.0% Known or suspected neoplasia–2.4%New dermal, epidermal or subcutaneous masses (unsampled)–19.0% ApoquelLong Term (mean of 401 days) –Hematological Side EffectsTransient decreases in WBCNeutrophils, Eosinophils, MonocytesTransient decrease

5 s in plateletsTransient increase in chol
s in plateletsTransient increase in cholesterolTransient increase in total proteinDogs with abnormal BUN, Creatinine, and ALP at enrollment were unaffectedTwo dogs (1 with ALT and 1 with ALP) were withdrawn Atopic dermatitisAdverse food reactionFlea allergy dermatitisSarcoptesscabieiFeline idiopathic ulcerative dermatitisFeline cutaneous mastocytosisSterile eosinophilic 5 Side Notes Apoquel–Personal Clinical ExperienceImmune

6 mediated/granulomatous diseasesFlare up
mediated/granulomatous diseasesFlare up when decreased to SIDErythematous dogsOther side effects CapsulesLiquid 6 Human versionSandimmuneCompounded mRNARNA polymeraseof DNA Translationof mRNA cytoplasmiccalcium (CaNFAT (Nuclear factor of activated T-cells, a transcription factor)Cell function presenting MHC Cyclosporine binds cyclophilin, which inhibits calcineurin Inhibition works upstream blocking pro-inflammatory cyt

7 okines such as IL-2, and pro-inflammator
okines such as IL-2, and pro-inflammatory pathways NFAT T cell Cyclosporine CsCyclosporine Cs Cs Cs Cs 7 Dogs –5 mg/kg PO SID either 2 hours after a meal or 1 hour prior to a mealCats –7 mg/kg PO SID either 2 hours after a meal or 1 hour prior to a mealUp to 6-8 weeks for clinical improvement DiarrheaHypertrichosisGingival hyperplasia Atopic dermatitisNumerous dermatologic immune mediated 7-10 mg/kg q24hNumerous systemic im

8 mune mediated diseases10-20 mg/kg q12-24
mune mediated diseases10-20 mg/kg q12-24hr 8 AtopicaDrug InteractionsCytochrome P-450InhibitorsKetoconazole, Fluconazole, Itraconazole, Grapefruit JuiceRifampin, Phenobarbitol, St. John’s Wart Atopica–Personal Clinical ExperienceDrug administrationErythematous dogsAtopicafor cats You name it! 9 mRNARNA polymeraseof DNAinto cell membraneTranslationof mRNA receptor –proteincomplexProtein complexdimerizationCell function Change

9 s happen in every cell of the body since
s happen in every cell of the body since corticosteroidreceptors are in every cell Glucocorticoids Gc Gc Gc Gc Gc Gc Gc Gc GcGlucocorticoid • Polydipsia / Polyuria• Mood changesLYMPH NODES• Suppression of the immune system• LymphopeniaHEART & BLOOD VESSELS• Water retention• Muscle weakeningMUSCLE• Thinning• Weakness• Pendulous abdomen• Temporal muscle atrophyREFERENCE:Boothe, Dawn Merton. Small Animal Clinical Pharmacolog

10 y and Therapeutics. WB Saunders. Philade
y and Therapeutics. WB Saunders. Philadelphia 2001. P326-228.LIVER• Fat accumulation• Elevated liver enzymesADRENAL GLANDS• Suppression or iatrogenic hyperadrenocorticism (Cushing’s disease)KIDNEYS• Polyuria• Altered electrolyte balance• Protein losing glomerulonephropathyPANCREAS• Predisposed for type II diabetes• Predisposed for pancreatitisBLADDER• Increased susceptibility to infectionSKIN & FUR• Hair loss• Thinn

11 ing of the skin• Increased susceptibilit
ing of the skin• Increased susceptibility to infection• Calcinosis cutis Steroid Side Effects 10 Anti-inflammatory –Dog -0.5-1 mg/kg q24h-Cat -1-2 mg/kg q24hImmunosuppressive –Dog -2-4 mg/kg q24h-Cat –4-8 mg/kg q24h DosingCaution when using different forms of corticosteroids Personal Clinical ExperienceLast optionsOwner resistance 11 Canine Atopic Dermatitis Immunotherapeutic (CADI) -ZoetisFDA Conditional License –Full l

12 icense expected late 2016 Lokivetmab–IL-
icense expected late 2016 Lokivetmab–IL-31 monoclonal antibodyApproximately once monthly subcutaneous 19-105 day range om/products/dogs/il- 31/moa.aspx Canine Atopic Dermatitis Immunotherapeutic (CADI) -Zoetis Canine Atopic Dermatitis Immunotherapeutic (CADI) -ZoetisQuick onset of actionRare side effects 12 Canine Atopic Dermatitis Immunotherapeutic (CADI) -ZoetisClinical experience Which treatment is best for your AD patien