DOCSLIB.ORG

Recombinant Human Interferon-Alpha 14 for the Treatment of Canine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recombinant Human Interferon-Alpha 14 for the Treatment of Canine Received: 8 June 2020 Revised: 15 January 2021 Accepted: 3 February 2021 DOI: 10.1002/vro2.6 RESEARCH ARTICLE Recombinant human interferon-α for the treatment of canine allergic pruritic disease in eight dogs Breno C. B. Beirão, Aline C. Taraciuk Carolina Trentin Max Ingberman Luiz F. Caron Chris McKenzie William H. Stimson, 1 Imunova Análises Biológicas LTDA, Curitiba, Abstract Brazil Background: Allergic pruritic diseases are increasingly common in dogs. This group 2 Departamento de Patologia Básica, Universidade of conditions hampers life quality as pruritus progressively interferes with normal Federal do Paraná, Curitiba, Brazil behaviours. Therefore, new treatment modalities for canine allergic pruritic diseases are 3 Veterinary Consultant, Avenida Nossa Senhora necessary. While novel drugs have recently reached the market, there is still the need for de Lourdes,63, Curitiba, Brazil other therapeutic approaches. Some dogs are refractory even to the newer compounds, 4 ILC Therapeutics Ltd. Biocity, Scotland, and cost is also an important issue for these. Older therapeutic modalities are only mod- Lanarkshire, UK erately successful or have considerable secondary efects, as is the case with glucocorti- 5 Immunology Department, Strathclyde University, Glasgow, Scotland, UK coids. Objectives: Report on the use of recombinant human interferon-α14 (rhIFN-α14) for Correspondence the treatment of canine allergic pruritus. Following the experience with a similar com- BrenoC.B.Beirão,ImunovaAnálisesBiológicas pound in the Japanese market, it was expected that rhIFN-α14couldaltertheTh1/Th2 LTDA,R.ImaculadaConceição,1430,Curitiba, disbalance that drives these diseases. 80215-182, Brazil. Email: [email protected] Methods: Here, we present an uncontrolled trial in which eight dogs with clinical diag- nosis of allergic pruritus were treated with rhIFN-α14,eitherorallyorviasubcutaneous Funding information: Imunova Análises Biológi- injections. Skin condition, microbiota and anti-interferon antibody levels were assessed. casLTDA;ILCTherapeuticsLtd. Results: The parenteral use of interferon induced hypersensitivity in two of the three dogs in which it was used. The oral administration was consistently safe and could reduce signs of the allergic condition in three of the fve treated animals. Treatment also altered the skin microbiota, as verifed by next-generation sequencing. Conclusion: The present results indicate that rhIFN-α14 is a viable candidate for the treatment of canine allergic pruritus. Future controlled studies are needed, and the oral route is indicated for further trials. KEYWORDS allergic, atopic dermatitis, dog, interferon, pruritic diseases INTRODUCTION the classical clinical manifestations of hypersensitivity. The disease therefore requires long-term treatment.1 Canine allergic pruritic diseases are a common condition in Standard-of-care therapies include several possible lines of dogs, characterised by dermatosis with intense pruritus and clinical intervention. Among these, the treatment of concur- infammation. Atopic dermatitis (AD) is the primary variety rent infections, the control of allergens and the use of anti- of allergic skin conditions.1 The most common clinical man- histamines, glucocorticoids (topically or systemically) and, ifestations are dry skin, erythema and self-induced excoria- more recently, a Janus Kinase inhibitor, oclacitinib.1 In Japan, tions, commonly at the scalp, face, neck and fexural surfaces canine interferon gamma has been used in the treatment of of the extremities.2 These allergic pruritic diseases – and AD AD. The goal of the therapy is to revert the Th1/Th2 immune in particular – occur due to excessive immune responses of the disbalance that leads to excessive IgE responses.3,4 Clinical CD4 Th2 ’phenotype’.These are usually due to genetic predis- efcacy was demonstrated in dog trials having antihistamine position, but environmental factors also play a role. The acti- as the active control.5 Here,wereporttheuseofrecombi- vation of this immune pathway leads to IgE production and nant human interferon-alpha14 (rhIFNα−14) in the treatment This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ©2021TheAuthors.Veterinary Record Open published by John Wiley & Sons Ltd on behalf of British Veterinary Association. Vet Rec Open. 2021;8:e6. wileyonlinelibrary.com/journal/vro2 of https://doi.org/10.1002/vro2.6 of Veterinary Record Open of canine allergic dermatitis.6 Previous work has shown the Blood samples were collected for haematological anal- molecule to interact with canine whole blood (unpublished ysis and for quantifcation of anti-interferon antibodies. data). A small-scale trial was conducted to assess safety and Samples were collected weekly whenever there was owner initial efcacy of rhIFNα-14. compliance. Therefore, sampling was not homogeneous between dogs throughout the test. Haematological analyses consisted of determination of blood cell counts, alkaline phos- MATERIALS AND METHODS phatase, urea, creatinine, total protein, protein fractions and AST levels. This was performed at the Veterinary Hospital at Thisstudywasdesignedasanopenuncontrolledtrial.Eight the Universidade Federal do Paraná. For the determination of dogs with chronic non-seasonal AD were selected. Dogs were adverse events, deviations in blood parameters that occurred enrolled based on previously published inclusion criteria.7 following drug administration were counted. ELISA for deter- Briefy, dogs had to have moderate to severe itching associated mination of canine anti-rhIFNα14 antibodies was performed with allergy based on history, clinical signs and owner com- in house. Briefy, MaxiSorp plates (Nunc) were coated with plaint. Dogs were otherwise healthy, were not in, and did not 100nginterferon/well.Theplatewasblockedwith1%casein require, active treatment for other conditions; dogs were not in phosphate bufered saline (PBS). Control wells were coated receiving and had not received immunosuppressants, antibi- with casein only. Plates were washed with PBS following each otics or antihistamines for 8 weeks prior to the study. Inclu- step. Serum was added in twofold dilutions for the deter- sion to the study was also based on elimination of resembling mination of titres. HRP-coupled anti-dog IgG was used for non-immune-mediated pruritic dermatoses by clinical assess- detection of bound antibodies (Alpha Diagnostics, 1:10,000 ment only. The owners received explanations about the trial, dilution). The reaction was developed with TMB liquid sub- andthestudyincludedthosewhoacceptedandcompletedthe strate (Life Scientifc). The absorbance of interferon-coated informed consent form. The study was performed under the wells was subtracted from the absorbance from control wells licenseoftheCommitteefortheUseofAnimalsinResearchof (coated with casein only) for the determination of specifc Imunova Análises Biológicas, protocol 003.2018. The trial was anti-interferon antibody titres. conducted according to the relevant international guidelines Long-term follow-up efcacy assessment was performed in ethics in the use of animals in research. with the best responders by communication with the owners All dogs were treated with the experimental compound. at 5 months post-trial. Owners were asked for the status of the Recombinant human interferon-alpha14 was produced in E. dogs and the time to return of pruritus. There was no clinical coli by Invigate GmbH, Jena, Germany and shown to be >98% assessmentofthedogsduringthefollow-upperiod. pure by SDS-PAGE and MS. The anti-viral bioactivity was Skin microbiota was assessed by next-generation sequenc- assessed by U-CyTech Biosciences, Utrecht, The Netherlands ing. Skin swabs were collected at treatment D0 and at the end and shown to be 1.8 × 108 IU/mg. Lyophilized interferon of the trial for three dogs. DNA was extracted from swabs was resuspended in 0.1% bovine serum albumin in saline using the ZR Fecal DNA MiniPrep (Zymo Research). The and was frozen in aliquots until the time of use. Three ani- variable V4 region of 16S rRNA was amplifed using the uni- mals received 10,000 IU/kg of rhIFNα−14 via subcutaneous versal primers 515F and 806R (Caporaso et al, 2011). PCR con- ◦ ◦ injection. The protocol for parenteral treatment consisted of ditions were as follows: 94 C,3minutes;18cyclesof94C, administration three times weekly for 4 weeks, then once 45 seconds, 50◦C, 30 seconds e 68◦C, 60 seconds; followed weekly for another 4 weeks. Five animals received the formu- by 72◦C, 10 minutes. These amplicons were then sequenced lation at the same dosage via oral administration, daily for (Illumina MiSeq). Sequencing reads were normalised at 8010 8 weeks. reads and analysed with the QIIME (Quantitative Insights ’Within-treatment’ follow-up was comprised of clinical into Microbial Ecology) platform (Caporaso et al, 2010, assessment and efcacy outcomes (veterinarian and owner 2011). Sequences were classifed into bacterial genera through assessments). Each dog was evaluated for the presence or the recognition of operational taxonomic units based on absence of papule, macula, pustules, dandruf, skin scabs, the homology at 97% of the sequences when compared to the lichenifcation, nodules, tumours, hyperkeratosis, vesicles, SILVA128 ribosomal sequence database (2017 release) (Yilmaz hyperpigmentation, erythema and alopecia by the veteri- et al, 2013). Basic
Load more

Recommended publications
  • CVMP Assessment Report for APOQUEL (EMEA/V/C/002688/0000) International Non-Proprietary Name: Oclacitinib Maleate
    18 July 2013 EMA/481054/2013 Veterinary Medicines and Product Data Management Committee for Medicinal Products for Veterinary Use CVMP assessment report for APOQUEL (EMEA/V/C/002688/0000) International non-proprietary name: oclacitinib maleate Assessment report as adopted by the CVMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8447 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged. Introduction The applicant Pfizer Animal Health S.A. submitted on 26 July 2012 an application for marketing authorisation to the European Medicines Agency (The Agency) for APOQUEL, through the centralised procedure falling within Article 3(2)(a) of Regulation (EC) No 726/2004 (new active substance). During the procedure the applicant changed to Zoetis Belgium S.A. The eligibility to the centralised procedure was confirmed by the CVMP on 12 January 2012 falling under Article 3(2)(a) of Regulation (EC) No 726/2004 as APOQUEL contains a new active substance which was not authorised in the Community on the date of entry into force of the Regulation. APOQUEL film-coated tablets contain oclacitinib (as oclacitinib maleate) as the active substance. There are three different strengths of the (film-coated) tablets, containing 3.6 mg, 5.4 mg and 16 mg oclacitinib (as the maleate salt), and each is contained in blister packs (polychlorotrifluoroethylene (PCTFE)/polyvinylchloride (PVC)/aluminium) which are supplied in outer cartons containing 20 or 100 tablets.
    [Show full text]
  • 5.10.20 Final Part 1 No Prelimeary Pages
    IDENTIFICATION OF NOVEL TREATMENT APPROACHES FOR HUMAN AND CANINE OSTEOSARCOMA By Ya-Ting Yang A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Comparative Medicine and Integrative Biology- Doctor of Philosophy 2020 ABSTRACT IDENTIFICATION OF NOVEL TREATMENT APPROACHES FOR HUMAN AND CANINE OSTEOSARCOMA By Ya-Ting Yang Osteosarcoma (OSA) is an aggressive neoplasm, characterized with high level of heterogeneity, high metastatic potential and poor prognosis in both humans and dogs. In this study, I used drug screening studies including existing therapeutic agents and novel compounds to identify more effective approaches to treat human and canine osteosarcoma. One of the challenges in the field of OSA is to identify optimal tools for study. A limited number of human and canine OSA cell lines are available. In this study, I established and characterized a new cell line, BZ, derived from a German shepherd dog with OSA and studied key oncogenic pathways in BZ. Our findings revealed activation of STAT3 and ERK pathways in BZ, as well as in a number of other cell lines, indicating that these two pathways are critical for cell survival and proliferation in OSA and the potential of using STAT3 and ERK inhibitors. Furthermore, I screened ten tyrosine kinase inhibitors (TKIs) on two dog and one human OSA cell lines. Among the selected TKIs, sorafenib showed promising results in effectively inhibited cell growth and migration in vitro studies. In addition, the effects of combing sorafenib with current chemotherapeutics (cisplatin, carboplatin, and doxorubicin) for OSA were investigated. Data from the combination index pointed to synergistic effects of sorafenib combined with doxorubicin and resulted in profound cell arrest at G2/M phase.
    [Show full text]
  • Successful Treatment of Atopic Dermatitis with the JAK1 Inhibitor Oclacitinib
    PROC (BAYL UNIV MED CENT) 2018;31(4):524–525 Copyright # 2018 Baylor University Medical Center https://doi.org/10.1080/08998280.2018.1480246 Successful treatment of atopic dermatitis with the JAK1 inhibitor oclacitinib Isabel M. Haugh, MB, BAO, BCha, Ian T. Watson,b and M. Alan Menter, MDa aDepartment of Dermatology, Baylor University Medical Center, Dallas, Texas; bTexas A&M College of Medicine, Bryan, Texas ABSTRACT We report the first case of atopic dermatitis successfully treated with the oral Janus kinase-1 (JAK1) inhibitor oclacitinib. A man in his 70s, with a 6-year history of skin disease refractory to topical and biologic therapies, self-prescribed this veterinary medication with rapid remission of symptoms. He has remained in remission for 7 months with no reported adverse side effects or infections. JAK1 plays a central role in expression of proinflammatory cytokines IL-4, IL-5, and IL-13, which play an important role in the pathogenesis of atopic dermatitis. Ruxolitinib and tofacitinib are JAK inhibitors currently approved by the Food and Drug Administration for the treat- ment of myelofibrosis, rheumatoid arthritis, and psoriatic arthritis in humans. Oclacitinib is not currently indicated for use in humans. KEYWORDS Atopic dermatitis; eczema; JAK1; oclacitinib clacitinib is a Janus kinase-1 (JAK1) inhibitor DISCUSSION approved for the treatment of pruritus secondary Oclacitinib selectively inhibits JAK1 of the JAK signal O to allergic dermatitis and atopic dermatitis in transducer and activator of transcription (JAK-STAT) path- canines. JAK1 plays a role in the expression of way, which plays a central role in cytokine signaling of pro- interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 inflammatory cytokines in atopic dermatitis, both in dogs (IL-13) in proinflammatory signaling pathways known to and in humans.
    [Show full text]
  • Safety and Toxicity of Combined Oclacitinib and Carboplatin Or Doxorubicin in Dogs with Solid Tumors: a Pilot Study Laura E
    Barrett et al. BMC Veterinary Research (2019) 15:291 https://doi.org/10.1186/s12917-019-2032-4 RESEARCH ARTICLE Open Access Safety and toxicity of combined oclacitinib and carboplatin or doxorubicin in dogs with solid tumors: a pilot study Laura E. Barrett1, Heather L. Gardner2, Lisa G. Barber1, Abbey Sadowski1 and Cheryl A. London1* Abstract Background: Oclacitinib is an orally bioavailable Janus Kinase (JAK) inhibitor approved for the treatment of canine atopic dermatitis. Aberrant JAK/ Signal Transducer and Activator of Transcription (STAT) signaling within hematologic and solid tumors has been implicated as a driver of tumor growth through effects on the local microenvironment, enhancing angiogenesis, immune suppression, among others. A combination of JAK/STAT inhibition with cytotoxic chemotherapy may therefore result in synergistic anti-cancer activity, however there is concern for enhanced toxicities. The purpose of this study was to evaluate the safety profile of oclacitinib given in combination with either carboplatin or doxorubicin in tumor-bearing dogs. Result: Oclacitinib was administered at the label dose of 0.4–0.6 mg/kg PO q12h in combination with either carboplatin at 250-300 mg/m2 or doxorubicin at 30 mg/m2 IV q21d. Nine dogs were enrolled in this pilot study (n =4 carboplatin; n = 5 doxorubicin). No unexpected toxicities occurred, and the incidence of adverse events with combination therapy was not increased beyond that expected in dogs treated with single agent chemotherapy. Serious adverse events included one Grade 4 thrombocytopenia and one Grade 4 neutropenia. No objective responses were noted. Conclusions: Oclacitinib is well tolerated when given in combination with carboplatin or doxorubicin.
    [Show full text]
  • TITLE PAGE PASS Information
    TITLE PAGE PASS information Title Project Sc(y)lla: SARS-Cov-2 Large-scale Longitudinal Analyses on the comparative safety and effectiveness of treatments under evaluation for COVID-19 across an international observational data network Protocol version 1.1 identifier Date of last version of 28August2020 protocol EU PAS register number To be completed after protocol finalization Active substance Medicinal product Research question and The overarching objective is to evaluate the objectives comparative effects of COVID-19 treatments Country(-ies) of study France, Germany, Netherlands, South Korea, Spain, UK, and the USA. Others might join in the future. Authors Patrick Ryan Daniel Prieto-Alhambra on behalf of the OHDSI COVID consortium 1. TABLE OF CONTENTS 1. Table of contents ............................................................................................................................................. 2 2. List of abbreviations......................................................................................................................................... 3 3. Responsible parties .......................................................................................................................................... 3 5. Amendments and updates .............................................................................................................................. 4 7 Rationale and background...............................................................................................................................
    [Show full text]
  • APOQUEL® (Oclacitinib Tablet): Fast-Acting and Safe Itch Relief For
    APOQUEL® (oclacitinib tablet): Fast-Acting and Safe Itch Relief for Dogs Your veterinarian has recommended APOQUEL to help control your dog’s itch due to allergic skin disease. APOQUEL provides fast, effective relief from itch and inflammation without many of the side effects associated with steroids.1-3* *Common side effects of steroids include polyuria, polydipsia and polyphagia. Side effects of APOQUEL reported most often are vomiting and diarrhea. WHAT IS ALLERGIC SKIN DISEASE? Itching in dogs can be caused by fleas, food or environmental allergens such as pollens, molds or house-dust mites. The 4 most common allergies are: CONTACT ALLERGY ENVIRONMENTAL INDOOR FLEA FOOD (carpet, shampoo, AND OUTDOOR ALLERGENS ALLERGY ALLERGY environmental chemicals— (pollen, dust mites, or mold) insecticides, fertilizers) WHAT IS APOQUEL USED FOR? APOQUEL is used for the control of itch associated with allergic skin disease and for control of atopic skin disease in dogs at least 12 months of age. APOQUEL significantly reduces itching, and also decreases the associated inflammation, redness or swelling of the skin. WHAT CAN I EXPECT WHEN MY DOG RECEIVES APOQUEL? Fast Relief Unique Treatment APOQUEL starts to relieve itch within 4 hours, Unlike other treatments, APOQUEL targets a key itch signal in which is comparable to steroids. 3 the nervous system and has minimal impact on the immune system. APOQUEL effectively controls itch within 24 hours.1 APOQUEL also allows your veterinarian to continue to diagnose the underlying cause of itch while providing your dog with relief. 3,4 Safety APOQUEL is safe to use in dogs 12 months of age and older.
    [Show full text]
  • Development and Progression of Proteinuria in Dogs Treated with Masitinib for Neoplasia: 28 Cases (2010-2019)
    / PAPER Development and progression of proteinuria in dogs treated with masitinib for neoplasia: 28 cases (2010-2019) M. Kuijlaars1,*, J. Helm* and A. McBrearty* a.com *Small Animal Hospital, University of Glasgow, Glasgow, Scotland, G611QH, UK 1Corresponding author email: [email protected] v OBJECTIVES: To describe the incidence, severity and progression of proteinuria over the first 6 months of masitinib treatment in tumour-bearing dogs without pre-existing proteinuria. To describe the effect of treatment on urine protein:creatinine and renal parameters in patients with pre-existing proteinuria. MATERIALS AND METHODS: Records were reviewed from patients receiving masitinib for neoplasms between June 1, 2010, and May 5, 2019. Patients without pre-treatment and at least one urine protein:creatinine after ≥7 days treatment were excluded. Signalment, tumours and concurrent diseas- es, treatments, haematology, biochemistry and urinalysis results before, during and after treatment for up to 202 days were collected. Patient visits were grouped into six timepoints for analysis. .bsa RESULTS: Twenty-eight dogs were included. Eighteen percent of dogs non-proteinuric at baseline (four of 22) developed proteinuria during treatment, all within 1 month of treatment initiation. One dog developed hypoalbuminaemia, none developed oedema or ascites, azotaemia or were euthana- sed/died due to proteinuria. Masitinib was immediately discontinued in both dogs in which urine protein:creatinine greater than 2.0 was detected and in both, proteinuria improved. Six dogs with pre-treatment proteinuria were treated with masitinib, significant worsening of protein- uria did not occur. Neither azotaemia nor severe hypoalbuminaemia occurred. CLINICAL SIGNIFICANCE: Proteinuria, when it occurs, tends to develop within 1 month of masitinib com- mencement and may progress rapidly.
    [Show full text]
  • Supplementary Materials
    1 Supplementary Materials Figure S1. Flowchart of the Material and Methods: PRISMA flow diagram of the study. RCT, randomized controlled trial. 2 Table S1. Search strategies modified in MEDLINE (a), Embase (b), Cochrane CENTRAL (c), and Web of Science (d) a. Search strategy in MEDLINE (via Ovid MEDLINE(R), 1946–present; search date: 2021/01/29) # Search syntax Citations found 1 ("atopic dermatitis" OR eczema*).mp 2 exp "Dermatitis, Atopic"/ OR exp "Eczema"/ 3 ((Janus ADJ3 kinase* ADJ3 inhibit*) OR (JAK* ADJ3 inhibit*) OR Abrocitinib OR "PF-04965842" OR Baricitinib OR LY3009104 OR Olumiant OR INCB028050 OR Delgocitinib OR "JTE-052" OR Gusacitinib OR ASN002 OR Ruxolitinib OR INCB018424 OR INCA24 OR Tofacitinib OR Tasocitinib OR "Tofacitinib citrate" OR Xeljanz OR CP690550 OR Upadacitinib OR "ABT-494" OR RINVOQ OR Cerdulatinib OR "RVT-502" OR PRT062070 OR Peficitinib OR ASP015K OR Filgotinib OR GLPG0634 OR Solcitinib OR "1206163-45-2" OR GLPG0778 OR GSK2586184 OR SHR0302 OR "ATI-502" OR "ATI 50002" OR "A 301" OR "PF- 06700841" OR "RVT-501" OR Decernotinib OR "VX-509" OR Pacritinib OR SB1518 OR Oclacitinib OR Apoquel OR "PF-03394197" OR Fedratinib OR TG101348 OR SAR302503 OR "Fedratinib hydrochloride" OR Inrebic).mp 4 exp "Janus Kinase Inhibitors"/ 5 (1 OR 2) AND (3 OR 4) 195 b. Search strategy in Embase (via Ovid, 1974–present; search date: 2021/01/29) # Search syntax Citations found 1 ("atopic dermatitis" OR eczema*).mp 2 exp "atopic dermatitis"/ OR exp "eczema"/ 3 ((Janus ADJ3 kinase* ADJ3 inhibit*) OR (JAK* ADJ3 inhibit*) OR Abrocitinib
    [Show full text]
  • Veterinary Dermatology and the Human Counterpart
    “PARALLELS AND DIVERGENCE”: VETERINARY DERMATOLOGY AND THE HUMAN COUNTERPART Jackie Campbell, DVM, Diplomate ACVD Disclosure I have no actual or potential conflict of interest in relation to this program/presentation. Dermatology for Animals? Common diseases we treat and parallels Atopic Dermatitis and Cutaneous Adverse Food Reactions Immune mediated diseases: Pemphigus Complex, Uveodermatologic Syndrome, Vasculitis Neoplasia: Squamous cell carcinoma, Cutaneous T cell Lymphoma Miscellaneous “fun” stuff Zoonotic Aspect What can our patients give your patients? Methicillin resistant staphylococcus Dermatophyte Sarcoptes Allergen dander contribution Canine Atopic Dermatitis The most common dermatologic disease we treat in all species Canine atopic dermatitis increasingly common disease Pruritus Secondary pyoderma Secondary Malassezia Otitis Pododermatitis Clinical Signs Palmar aspect of carpi Periocular and Perioral Canine Atopic Dermatitis Comparable counterpart to human AD Pruritus, erythema Conjunctivitis, rhinitis not typical Pruritus frustrating for pet owners Secondary skin infections Secondary pyoderma Resistant Staph Pseudintermedius increasingly common Malassezia dermatitis Typically progressively worsens with age Classic Collarettes Hypothesis of Canine AD Genetic mutations associated with impaired epidermal barrier Filaggrin, ceramides Alterations in microbiome Breed predisposition Development of allergen specific IgE Th2 mediated response in acute phase IL4, IL6, IL13, IL31 Th1 shift in more
    [Show full text]
  • Leveraging Comparative Oncology to Maximize Translational Outcomes
    Leveraging Comparative Oncology to Maximize Translational Outcomes Cheryl London, DVM, PhD Research Professor, Tufts University Associated Faculty Professor, Ohio State University Consortium for Canine Comparative Oncology (C3O) Symposium Thomas Executive Conference Center, JB Duke Hotel February 17, 2017 High failure rate in oncology drug development Failure rate is not financially sustainable Amid flurry of new cancer drugs, how many offer real benefits? By Liz Szabo, Kaiser Health News Updated 4:01 AM ET Story highlights •Pushed by those who want earlier access to medications, FDA has approved a flurry of oncology drugs in recent years •A few have been home runs, allowing patients with limited life expectancies to live for years •But many more offer only marginal benefits, a researcher says Overall cancer survival has barely changed over the past decade. The 72 cancer therapies approved from 2002 to 2014 gave patients only 2.1 more months of life than older drugs, according to a study in JAMA Otolaryngology-Head & Neck Surgery. And those are the successes. Two-thirds of cancer drugs approved in the past two years have no evidence showing that they extend survival at all. The result: For every cancer patient who wins the lottery, there are many others who get little to no benefit from the latest drugs. Reasons for Failure Other 6% Financial 7% Safety 21% Efficacy 66% Most rodent models lack critical features of spontaneous neoplasia Many models use immunodeficient mice that lack key microenvironment components Cancer typically develops
    [Show full text]
  • Apoquel (Oclacitinib)
    Oclacitinib (ok-la-sit-ti-nib) Category: Anti-Itch & Anti-Inflammatory Agent Other Names for this Medication: Apoquel® Common Dosage Forms: Veterinary: 3.6 mg, 5.4 mg, & 16 mg tablets. Human: None. This information sheet does not contain all available information for this medication. It is to help answer commonly asked questions and help you give the medication safely and effectively to your pet. If you have other questions or need more information, contact your veterinarian or pharmacist. This drug SHOULD NOT be used in patients: Key Information XXThat are allergic to it. XXBecause oclacitinib is a new medication, be sure to report XXWith serious infections. any unexpected side effects to your veterinarian. XXThat are less than 12 months old. XXOclacitinib works quickly. Many dogs show improvement within the first few days of treatment. XXThat are used for breeding or are pregnant or lactating. XXThe most commonly reported side effects are vomiting, This drug should be used WITH CAUTION in patients: diarrhea, lack of appetite, increased thirst, and lethargy. XXWith ongoing infections. XXSerious side effects, including increased risk of infections If your pet has any of these conditions, talk to your veterinarian and skin disorders, are possible. about the potential risks versus benefits. XXThis medication is usually given twice a day for the first 2 weeks then decreased to once a day. What are the side effects of this medication? Due to its recent approval and limited clinical use, oclacitinib’s XXWash hands immediately after handling tablets. adverse effect profile is not fully known. Side effects commonly reported that usually are not serious include: How is this medication useful? XXVomiting, diarrhea, lack of appetite.
    [Show full text]
  • N141345 Apoquel Untitled Letter
    Dawn M. Cleaver, DVM Associate Director, Regulatory Affairs Zoetis, Inc. 333 Portage Street Kalamazoo, MI 49007 RE: NADA 141-345 APOQUEL® (oclacitinib tablet) Dear Dr. Cleaver, The U.S. Food and Drug Administration (FDA), Center for Veterinary Medicine (CVM), Division of Surveillance has reviewed the website for APOQUEL (oclacitinib tablet), https://www.zoetisus.com/products/dogs/apoquel/index.aspx. This website makes false or misleading representations about the risks associated with APOQUEL. The website therefore misbrands APOQUEL within the meaning of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and makes its distribution violative. 21 U.S.C. 352(a), (n); 321(n); 331(a). Background Below are the indication and summary of the most serious and most common risks associated with the use of APOQUEL. According to the FDA-approved package insert (PI), APOQUEL is indicated for the control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age. The PI contains warnings and precautions including the following: (1) should not be used in dogs with serious infections; (2) may increase susceptibility to infection, including demodicosis, and exacerbate neoplastic conditions; (3) is not for use in breeding dogs, or pregnant or lactating bitches; (4) has not been evaluated in combination with glucocorticoids, cyclosporine, or other systemic immunosuppressive agents; and (5) dogs receiving APOQUEL should be monitored for the development of infections, including demodicosis, and neoplasia. U.S. Food and Drug Administration Center for Veterinary Medicine 7500 Standish Place Rockville, MD 20855 www.fda.gov False or Misleading Risk Presentation Promotional materials misbrand a drug if they are false or misleading with respect to risk or benefits.
    [Show full text]