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ACTUALITÉS 2021 DOULEURS CHRONIQUES
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BIOTHERAPIES
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o Thérapies cellulaires: cellules soucheso Thérapies tissulaires: greffes de tissus vivantso Thérapies géniques: transfert de gènes, intervention sur les gèneso Thérapies copiant des molécules naturelles du corps humain et synthétisés
par des bactéries ou des cellules: 1°Anticorps monoclonaux
chimérique « XI »: Infliximab, rituximabhumanisé 90% « ZU »: tocilizumab, certolizumabhumanisé 100% « MU »: golimumab, adalimumab,
2°Facteurs de croissance 3°Protéines recombinantes: Etanercept
BIOTHERAPIESProduction de médicaments et de stratégies thérapeutiques
basés sur le vivant.
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Cellules de la paroi du cordon (Gelée de Warthon)Prolifération +++ Différenciation +++ Immunomodulation +++
Cellule souche = cellule indifférenciée:1° Potentiel de différenciation en au moins un type cellulaire.2° Auto-renouvellement en maintenant un état indifférencié
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Différenciation chondrocytaire des CSM
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Activité paracrine des CSM
o ↓ Apoptose: mort cellulaire programméeo ↑ Angiogenèseo ↓ Fibroseo ↑ Chondrogenèse endogène / biofacteurs
o 1ère étape: exposition CSM aux cytokines pro-infl: TNF𝛼 - Il-1 …
o Acquisition propr. immunorégulatrices
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Activité paracrine des CSM: ↑ cytokines et facteurs de croissance
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Activité paracrine des CSM
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CELLULES SOUCHES NEONATALES
Médecine régénérativePotentiel de différenciation cellulaire ?
☞ Facteurs de croissance :
o Anti-inflammatoireso Anti-fibrotiqueso Anti-apoptotiqueo Immunomodulatriceso Angiogenèse o ↓ MMP
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Betty Mastiff F 7 ans 67 kgArthrose Grassets D et G
Intolérance AINSDouble TPLO refusée
Tramadol: 200 mg le matin 100 mg le soir
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Dolodog evaluation showed a score of 31out of 60:o behavioral component 7 out of 12o functional component 20 out of 28o neuropathic component 0 out of 12o interactive component 4 out of 8…meaning severe pain.
et’
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11/04/17
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+ 26 MOIS
+ 3 ANS 3MOIS11 ans
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Capri Retriever F 10 ans 38,3 kgArthrose Grassets D et G
SB: 4Dolodog: 34/60 Douleurs sévères
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Douleurs mixtes: Per et Post-opératoires + Arthrose Joy Epagneul Breton F 11ans 19,20 kgRupture LCA D - Coxarthrose - Arthrose coudes
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+ 15 Jours + 6 Mois
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+ 22 mois
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+ 2 ans / Visioconsultation
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Hatchie Cane corso M 7 ans 54 kg Arthrose coudesExérèse Pr. Anconé Coude D Retard cicatrisation: Ondes de choc
o Boiteries intermittenteso Gabapentine 300 BIDo Sédationo Intolérance Amantadineo Trocoxilo Chondroprotecteurso Infiltration HAo Hyalonate IV
Ce que je souhaite : Que Hatchi ne souffre plus !
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Gabapentine 300 BIDCSMPEA
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Florette Labrador F 9 ans 37 kg CoxarthroseRupture LCA D et G: TPLO
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o Ponction par voie latéraleo Juste dorsalement au grand trochantero Aiguille dirigée médialement
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Pilot Clinical Study 1 After Knee (TPLO) Surgery
Double Blinded Study –Comparison to 1 Month NSAID
after surgery
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Treatment/Design:
Results: (n = 14)
o No side effects with MSC (clinical evaluation)o Similar clinical score and lameness
after TPLO in both groupso Faster bone healing with MSC (radiography)
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Pilot Clinical Study 2 A Single Injection in Advanced
Osteoarthritis – No NSAIDClinical Improvement Assessment
by Vet and Pet’s Owner
ORIGINAL RESEARCHpublished: 05 February 2019
doi: 10.3389/fvets.2019.00010
Frontiers in Veterinary Science | www.frontiersin.org 1 February 2019 | Volume 6 | Article 10
Edited by:
Ashlee E. Watts,Texas A&M University, United States
Reviewed by:
Alix Kay Berglund,North Carolina State University,
United StatesMarina I. Garin,
Centro de Investigación Biomédica enRed de Enfermedades
Raras (CIBERER), Spain
*Correspondence:
Eric [email protected]
†These authors have contributedequally to this work
Specialty section:
This article was submitted toVeterinary Regenerative Medicine,
a section of the journalFrontiers in Veterinary Science
Received: 31 August 2018Accepted: 14 January 2019
Published: 05 February 2019
Citation:
Cabon Q, Febre M, Gomez N,Cachon T, Pillard P, Carozzo C,
Saulnier N, Robert C, Livet V, Rakic R,Plantier N, Saas P, Maddens S andViguier E (2019) Long-Term Safetyand Efficacy of Single or RepeatedIntra-Articular Injection of Allogeneic
Neonatal Mesenchymal Stromal Cellsfor Managing Pain and Lameness in
Moderate to Severe CanineOsteoarthritis Without
Anti-inflammatory PharmacologicalSupport: Pilot Clinical Study.
Front. Vet. Sci. 6:10.doi: 10.3389/fvets.2019.00010
Long-Term Safety and Efficacy ofSingle or Repeated Intra-ArticularInjection of Allogeneic NeonatalMesenchymal Stromal Cells forManaging Pain and Lameness inModerate to Severe CanineOsteoarthritis WithoutAnti-inflammatory PharmacologicalSupport: Pilot Clinical StudyQuentin Cabon1, Marine Febre 2, Niels Gomez1, Thibaut Cachon1,3, Paul Pillard 1,Claude Carozzo 1,3, Nathalie Saulnier 2, Clément Robert 2, Véronique Livet 1,Rodolphe Rakic 2, Nadia Plantier 2, Philippe Saas 4, Stéphane Maddens 2† andEric Viguier 1,3*†
1 Université de Lyon, VetAgro Sup, Centre Hospitalier Universitaire Vétérinaire, Marcy-l’Étoile, France, 2 Vetbiobank SAS,Marcy-l’Étoile, France, 3 Université de Lyon, VetAgro Sup, Interaction Cellule Environnement, ICE, Marcy-l’Étoile, France,4 INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur, Ingénierie Cellulaire et Génique, Université BourgogneFranche-Comté, Besançon, France
Objective: To explore the long-term safety and efficacy of canine allogeneic
mesenchymal stromal cells (MSC) administered intra-articularly as single or repeated
injections in appendicular joints of dogs affected by moderate to severe refractory
osteoarthritis.
Study Design: 22 pet dogs were recruited into a non-randomized, open and
monocentric study initially administering one cellular injection. A second injection was
offered after 6 months to owners if the first injection did not produce expected results.
Materials and Methods: Anti-inflammatory treatment (if prescribed) was discontinued
at last one week before the onset of treatment. Each injection consisted of at least 10
million viable neonatal allogeneic mesenchymal stromal cells obtained from fetal adnexa.
Medical data was collected from veterinary clinical evaluations of joints up to 6 months
post-injection and owner’s assessment of their dog’s mobility and well-being followed for
a further 2 years when possible.
Results: Mild, immediate self-limiting inflammatory joint reactions were observed in 5/22
joints after the first injection, and in almost all dogs having a subsequent injection. No
other MSC-related adverse medical events were reported, neither during the 6 months
follow up visits, nor during the long-term (2-years) safety follow up. Veterinary clinical
evaluation showed a significant and durable clinical improvement (up to 6 months)
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Objective vet’s clinical score Pet’s owner perception at 6 month and 2 years(LOAD survey)
Results at 6 months : (n = 25)o 86% of dogs still show clinical improvement after 6 months (pract. evaluation)o 72% of dogs’ owners report better mobility after 6 monthso 100% of them report absence of degradation of symptoms without NSAID
Results at 2 Years : (Dog’s owner evaluation)o 75% of dogs’ owners confirm a satisfactory mobility without NSAIDo 100% report absence of side effects after 2 years
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o Grasset fléchio Ponction par voie cranialeo Latéralement au ligament patellaire
entre la patelle et la crête tibialeo Aiguille dirigée caudalement à travers
le coussinet graisseux infra-patellaire
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Epicondyle Huméral Médial
Sommet Olécrane
Ouverture interligne/ Abduction + Rotation externe
1/2
Direction médiale et distale
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o Ponction par voie caudo-latéraleo Distalement et caudalement à
l’acromion le long du bord caudal du chef acromien du deltoïde
o Aiguille en direction médiale
o Carpe fléchio Ponction par voie dorsaleo Dépression entre le radius distal et la 1ère
rangée du carpeo Entre l’extenseur commun des doigts
latéralement et l’extenseur radial du carpe médialement
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o Ponction par voie crânialeo Tarse étenduo Entre le pilon tibial et la lèvre du taluso Aiguille dirigée caudalement
o Ponction par voie caudaleo Tarse fléchio Entre la malléole fibulaire et le pilon tibialo Aiguille dirigée dorso-médialement le long
du calcanéum
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Therapeutic Efficacy of Fresh, AllogeneicMesenchymal Stem Cells for Severe Refractory FelineChronic GingivostomatitisBOAZ ARZI ,a KAITLIN C. CLARK ,b AYSWARYA SUNDARAM,b MATHIEU SPRIET,aFRANK J.M. VERSTRAETE,a NAOMI J WALKER,b MEGAN R. LOSCAR,c NASIM FAZEL,dWILLIAM J MURPHY,d NATALIA VAPNIARSKY,e DORI L. BORJESSONbKey Words. Adipose-derived stem cells • Fresh • Allogeneic • Cats • Gingivostomatitis •
Oral Mucosa • ImmunomodulationABSTRACTMesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promisingtherapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacyof fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS),a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investi-gate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs werealso tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 monthapart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASCcrossmatching and serum proteins and cytokine concentrations were determined. Four of the 7cats (57%) responded to treatment [complete clinical remission (n 5 2) or substantial clinicalimprovement (n 5 2)]. Three cats were nonresponders. Prior to therapy, most cats had increasedcirculating CD81 T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinicalresolution was not associated with normalization of these parameters. Nonresponders showedmore severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferongamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remissiontook up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCswere identified in the oral cavity of FCGS affected cats than the control cat. The administration offresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as comparedto the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenicASCs may differ in this model of oral inflammation. STEM CELLS TRANSLATIONAL MEDICINE2017;00:000–000SIGNIFICANCE STATEMENTThis study is the first to demonstrate the safety and efficacy of fresh, allogeneic adipose derivedstem cells systemic therapy for a naturally occurring, inflammatory disease in cats. We demon-strate that this therapy resulted in delayed clinical and histological resolution and immune mod-ulation as compared to autologous therapy. We also demonstrated that the mechanism(s) ofaction for autologous and allogenic adipose-derived MSCs (ASCs) may differ in this model oforal inflammation. Finally, we show that ASC in cats are initially engrafted to the lungs and thata higher fraction of cells were identified in the oral cavity of feline chronic gingivostomatitisaffected cats than control.INTRODUCTIONStem cell-based therapy and research have madeexceptional progress in the last decade. Apartfrom their capacity to regenerate damaged tis-sues, mesenchymal stem cells (MSCs) possessunique immunomodulatory capabilities and haveimproved the outcome of clinical diseases withaberrant immune responses [1–4]. We recentlypublished on the safety and efficacy of autologous
adipose-derived mesenchymal stem cells (ASCs)to treat naturally occurring feline chronic gingivos-tomatitis (FCGS). FCGS is a large animal model ofimmune-mediated oral mucosal inflammatory dis-eases of humans including oral lichen planus(OLP), recurrent aphthous stomatitis, pemphigus,and pemphigoid [1]. In both human and cats,these diseases result in painful mucosal lesionsthat markedly reduce quality of life and oftenrequire long-term immunosuppressive therapy
aDepartment of Surgical andRadiological Sciences,bDepartment of Pathology,Microbiology andImmunology, School ofVeterinary Medicine,cWilliam R. PritchardVeterinary Medical TeachingHospital, dDepartment ofDermatology, School ofMedicine, eDepartment ofBiomedical Engineering,University of California,Davis, California, USA
Correspondence: Boaz ArziDVM, DAVDC, DEVDC, AssociateProfessor, Department ofSurgical and RadiologicalSciences, School of VeterinaryMedicine, University ofCalifornia, Davis, One GarrodDrive, Davis, California, 95616,USA. Telephone: (530) 752-2470;Fax: (530) 754-5739; e-mail:[email protected]
The work was performed atthe Department of Surgicaland Radiological Sciences andthe Department of Pathology,Microbiology and Immunology,School of Veterinary Medicine,University of California, Davis.
Received February 15, 2017;accepted for publication May 9,2017
Oc AlphaMed Press1066-5099/2017/$30.00/0
http://dx.doi.org/10.1002/sctm.17-0035
This is an open access articleunder the terms of the CreativeCommons Attribution-NonCommercial-NoDerivsLicense, which permits use anddistribution in any medium,provided the original work isproperly cited, the use is non-commercial and no modificationsor adaptations are made.
STEM CELLS TRANSLATIONAL MEDICINE 2017;00:00–00 www.StemCellsTM.com Oc 2017 The AuthorsSTEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
ENABLING TECHNOLOGIES FOR CELL-BASED CLINICALTRANSLATION
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+ 4 Mois
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ANTICORPS MONOCLONAUX
Thierry Poitte DMV DIU Douleur CES Traumatologie et Chirurgie Ostéo-Articulaire île de Ré 2021
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ANTICORPS MONOCLONAUX
Immunoglobulines (Ig) monoclonales produites par des cellules en culture et spécifiques d’une cible thérapeutique
o Un anticorps monoclonal (AcM) est un anticorps reconnaissant un seul épitope sur un antigène donné
o Par définition produit par un seul clone de plasmocyte.
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Glycoprotéines formées de 2 régions:
1°Région Fab: Fragment antigen binding ☞ liaison très spécifique à l’antigène cible
o Ag circulants: cytokines, protéines, Ig, médicaments…o Ag membranaires
2°Région Fc: Fragment cristallisable☞ interaction avec le système immunitaire inné (réponse non spécifique)
o Activation du système du complément
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Cible = NGF Nerve Growth Factor Neurotrophines
Fibres C
o Acteur clé de la neuroplasticitéPronociceptif chez l’adulte si surexpression NGF
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NGF Acteur clé de la neuroplasticité
o Fixation sur TrkAo Médiateur périphérique des douleurs inflammatoires o ↑ Réponse TRPV ASIC P2X3o Sensibilisation périphérique
o Fixation sur TrkBo Sensibilisation centrale
LibérationCDME
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Mantyh PW et al. Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain. Anesthesiology, V 115 • No 1 July 2011
80% des fibres innervant l’os = fibres nociceptives (Aδ et C)exprimant TrkA, récepteur au Nerve Growth Factor☞ sensibles au NGFSeulement 30% des fibres innervant la peau sont TrkA+
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Douleur Inflammation
Blocage TrkA
Nocicepteurs Mastocytes
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When compared to placebo, NV-02 was safeand showed improvement of pain in cats treated at 2.0 mg/kg in a model study and at0.4 and 0.8 mg/kg in a PoC field study in feline patients.
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Métabolisme des AcMc
o Résorption : Injection SC : biodisponibilité = 50/100%o ½ vie très longueo Distribution : circulation sanguine – faible distribution tissulaireo Ne traverse pas la barrière hématoméningéeo Clairance :
ü La liaison à la cible !
ü Anticorps “anti-Acm” dans la circulation
ü Sortie des capillaires vers l’espace intersticiel, prise en charge par des cellules et catabolysé en AA ou recyclé
o Les Ac ne sont PAS métabolisés par des enzymes traditionnelles dans le foie ou le reinü Interactions médicamenteuses rares
ü Ne sont pas transformés en métabolites réactifs ou toxiques
o Les Ac ne sont PAS excrétés dans l’urine par le rein
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Anti NGFTanézumab Ω
o Etude clinique phase II chez des patients arthrosiques évaluant la douleur suite à 2 injections IV d’un anti-NGF
o 450 patients: 40 à 75 anso 76 / groupeo 10, 25, 50, 100 or 200 μg/kgo placebo o semaine 0 puis semaine 8o Efficacité ++++
o Fanizumab Ω
Lane N. Tanezumab for the Treatment of Pain from Osteoarthritis of the Knee . N Engl J Med 2010;363:1521-31.
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Doses approuvées FDA ?
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o EI graves 1,7% id placeboo Arthrose à évolution rapide
- Rapid Progression of OA (RPOA): 2,2%
o Ostéonécrose (+ rare)o Paresthésies – Dysesthésieso Fortes doseso si + AINSo Tabagisme
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RESEARCH ARTICLE Open Access
A canine-specific anti-nerve growth factor antibodyalleviates pain and improves mobility and functionin dogs with degenerative joint disease-associatedpainB Duncan X Lascelles1,2,3*, David Knazovicky1, Beth Case1, Mila Freire4, John F Innes5, Alexander C Drew6
and David P Gearing6
Abstract
Background: There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs fortreatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) areanalgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novelcaninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group,stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJDreceived NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, ownerscompleted clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory[CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS]and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change overtime. Recognized success/failure criteria were applied and success compared between groups.
Results: CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019;PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns witha significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), andsignificantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14,P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between thegroups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in theNV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between thegroups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006).
Conclusions: These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering fromchronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.
Keywords: Nerve growth factor, Dog, Antibody, Pain, Model, Osteoarthritis, Accelerometry, Actimetry
* Correspondence: [email protected] Pain Research Laboratory, Department of Clinical Sciences,College of Veterinary Medicine, North Carolina State University, Raleigh, NC,USA2Center for Comparative Medicine and Translational Research, College ofVeterinary Medicine, North Carolina State University, Raleigh, NC, USAFull list of author information is available at the end of the article
© 2015 Lascelles et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.
Lascelles et al. BMC Veterinary Research (2015) 11:101 DOI 10.1186/s12917-015-0413-x
Véto: NV-01 2 mg/mlo Anti NGF canino 200 μg/kg IV 60 seco 26 chienso 30 j efficacitéo Plateau de forces o CBPI - LOAD CSOM
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CSOM: Delta de 44 entre AcMc 67% succès et placebo 23% succèsVersus 26 entre meloxicam et placebo
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34 Chats OAPlacebo-controlled, pilot, maskedclinical study
o 11 chats: NV-02 0.4 mg/kg SC o 12 chats: 0.8 mg/kg SC o 11 chats: placebo saline SC
Evaluationo Actimétrieo CSOMo FMPIAmélioration: 6 semaines
A Feline-Specific Anti-Nerve Growth Factor Antibody ImprovesMobility in Cats with Degenerative Joint Disease–Associated Pain:
A Pilot Proof of Concept Study
M.E. Gruen, A.E. Thomson, E.H. Griffith, H. Paradise, D.P. Gearing, and B.D.X. Lascelles
Background: Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occur-ring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans.
Objectives: To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain andmobility impairment in cats.
Animals: Thirty-four client-owned cats with DJD-associated pain and mobility impairment.Methods: In a placebo-controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV-02
(0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Addi-tionally, owners completed clinical metrology instruments (client-specific outcome measures [CSOM] and feline musculoskele-tal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated-measures model was used to evaluatethe objective activity data.
Results: NV-02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4(P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a sig-nificant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified thetreatment administered compared with 45% of owners in the placebo group (P = .013). No treatment-related adverse effectswere identified.
Conclusions: These pilot data demonstrate a 6-week duration positive analgesic effect of this fully felinized anti-NGF anti-body in cats suffering from DJD-associated pain.
Key words: Client-specific outcome measures; Feline musculoskeletal pain index; Osteoarthritis.
Many adult and geriatric cats have radiographicevidence of degenerative joint disease (DJD),1,2
and a large proportion of these have associated chronicpain, manifested as alterations in mobility and activity.In the United States, there is no approved medicationfor the long-term treatment of chronic pain in cats,despite the clear need for such a treatment.Currently, the nonsteroidal anti-inflammatory drug
(NSAID) meloxicam is approved in Europe for use intreating chronic pain in cats, but has not been approvedfor this use in the United States. There are concerns
about the use of NSAIDs for long periods of time incats, especially because the majority of cats presentingwith DJD-associated pain have evidence of chronic kid-ney disease.3 Because of these concerns, dosages lowerthan the European-approved dosage of meloxicam havebeen tried, and there are several suggestions from open-label studies that these lower dosages are effective in themanagement of DJD-associated pain in cats.4,5 Only oneblinded, placebo-controlled study assessing a dosagelower than the approved 0.05 mg/kg daily dosage hasbeen performed, and that study found that a dosage of0.035 mg/kg daily produced measureable improvementover a 3-week period of administration.6,7 Indeed, only 2placebo-controlled, masked, clinical studies of the effi-cacy of meloxicam in cats have been published.6–8
Neutralizing antibodies against nerve growth factor(NGF) are analgesic in rodent models9 and in humans10
with chronic pain, although none currently are approvedfor use in humans. Using a proprietary technique forinterspecies conversion of antibodies based on expressedcDNA sequence analysis (PETizationTM) Nexvet
From the Comparative Pain Research Program, NCSU Collegeof Veterinary Medicine, Raleigh, NC (Gruen, Thomson, Paradise,Lascelles); Comparative Medicine Institute, NCSU College ofVeterinary Medicine, Raleigh, NC (Gruen, Lascelles); Departmentof Statistics, NC State University, Raleigh, NC (Griffith); NexvetAustralia Pty Ltd, Melbourne, VIC Australia (Gearing); and theCenter for Pain Research and Innovation, UNC Dental School,Chapel Hill, NC (Lascelles).Work was conducted at North Carolina State University,Comparative Pain Research Program, College of VeterinaryMedicine.
Corresponding author: B.D.X. Lascelles, Comparative PainResearch Program, NCSU College of Veterinary Medicine, 1060William Moore Drive, Raleigh, NC 27607; e-mails: [email protected]; [email protected].
Submitted February 1, 2016; Revised April 5, 2016; AcceptedApril 28, 2016.
Copyright © 2016 The Authors. Journal of Veterinary InternalMedicine published by Wiley Periodicals, Inc. on behalf of theAmerican College of Veterinary Internal Medicine.
This is an open access article under the terms of the CreativeCommons Attribution-NonCommercial License, which permits use,distribution and reproduction in any medium, provided the originalwork is properly cited and is not used for commercial purposes.
DOI: 10.1111/jvim.13972
Abbreviations:
AC activity counts
AM activity monitors
CMI clinical metrology instrument
CSOM client-specific outcome measures
DJD degenerative joint disease
FMPI feline musculoskeletal pain index
NCSU-CVM North Carolina State University College of Veterinary
Medicine
NGF nerve growth factor
OA osteoarthritis
J Vet Intern Med 2016;30:1138–1148
Gruen M et al. A Feline-Specific Anti-Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease–Associated Pain: A Pilot Proof of Concept Study. J Vet Intern Med 2016
65
NV-02 significantly increased objectively measured activity overall and at 2 , 3 , 4 , 5 and 6 weeks after treatment. CSOM scores and pain showed a significant effect of treatment 3 weeks afteradministration. No treatment-related adverse effects were identified.
CONCLUSIONS:
These pilot data demonstrate a 6-week duration positive analgesic effect of this fullyfelinized anti-NGF antibody in cats suffering from DJD-associated pain.
% variation d’activité: + 12,9%
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o Statistically significant top-line results seen in 3 week CSOM scores and other endpoints out to 5 weeks
o No adverse safety signals observed in PoC efficacy study or in separate high-dosage safety study
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Jump
Jump
Jump
Squat
Squat
Squat
Interactivity with family
Interactivity with family
Interactivity with family
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X
X
X
X
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101112
J0 J15 J30
Sauter S'accroupirInteract ions avec famille Score t otal
0123456789
101112
Sauter S'accroupir Interact ionsavec fami lle
Score t otal
J0 J15 J30
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o Atteinte polyarticulaireo Intolérance ou insuffisance résultats AINSo Co-morbidités IRC IH ICo 30 j efficacité
69
o Observanceo Co-morbidités IRC IH ICo Atteinte polyarticulaireo Intolérance ou insuffisance résultats AINSo 30 j efficacité
70
27/11/2020
36
Adaptée à de nombreux patients ∙ Douleurs arthrosiques et handicaps fonctionnels persistants ∙ Troubles du comportement en relation avec un mal-être ∙ Douleurs chroniques post-opératoires et di"cultés de récupération ∙ Douleurs cancéreuses ∙ Comorbidités douloureuses de l'animal senior ∙ Soins palliatifs ∙ Situations douloureuses d’impasse thérapeutique et d’errance médicale
S’appuyant sur une méthode originale
LA CONSULTATION CAPDOULEUR :
Supportée par des outils uniques
Engageant l’ensemble de l’équipe dans un projet innovant et motivant
C H A N G E A N I M A L P A I N
∙Vétérinaires (consultation douleur)
∙ASV (communication, recrutement, suivi)
∙Dolodog/Dolocat/Dolorabbit/CSOM
∙Pack de communication pour la clinique
∙ Ecoute réflexive ∙ Empathie ∙ Feedback ∙ Education thérapeutique ∙ Créneau horaire dédié
Suivant un déroulé précis1. Evaluation partagée avec le propriétaire
∙ Médecine narrative ∙ Grilles multiparamétriques digitales
2. Examen clinique attentionné
∙ Douleurs somatiques ∙ Douleurs viscérales ∙ Respectueux de l'état douloureux par la prévention des douleurs induites
3. Diagnostic des douleurs
∙ Inflammatoires ∙ Neuropathiques ∙ Fonctionnelles ∙ Centrales
4. Dé"nition partagée d’objectifs réalistes Qualité de vie
5. Co-décision thérapeutique
6. Complémentarité des moyens pharmacologiques, biothérapies et méthodes non pharmacologiques
7. Calendrier de suivi et d’observance
∙ Présentielle ∙ Téléconsultation
Alliance thérapeutique
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