PMID- 35720854
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231102
IS  - 2297-1769 (Print)
IS  - 2297-1769 (Electronic)
IS  - 2297-1769 (Linking)
VI  - 9
DP  - 2022
TI  - A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular 
      Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for 
      Osteoarthritis-Associated Joint Pain.
PG  - 836709
LID - 10.3389/fvets.2022.836709 [doi]
LID - 836709
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potential target for osteoarthritis (OA) 
      treatment. In several recent clinical studies in human OA, anti-TNF-alpha therapy 
      showed promising results; however, these were open-label and based on 
      patient-reported outcome measures. In this study, we developed a caninized TNF-alpha 
      receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, 
      open-label, pilot study in dogs with OA using objectively measured ground 
      reaction forces and activity. The aims of the study were to assess the efficacy 
      of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a 
      treatment for OA pain, and additionally to evaluate TNF concentrations in 
      synovial fluid (SF) between joints with/without OA in dogs. Dogs (n = 12) with 
      single-limb lameness due to single joint appendicular OA were recruited. All dogs 
      received caTNFR-Fc fusion protein injection into the affected joint under 
      sedation. Objective kinetic gait analysis using force plate was performed prior 
      to (baseline), and at 14- and 28-days following treatment. Additionally, SF 
      samples were collected from OA joints (n = 69) and non-OA joints (n = 79) in a 
      different cohort of dogs and TNF-alpha were measured using enzyme-linked 
      immunosorbent assay. No significant treatment effects on the limb use, activity, 
      and the questionnaire were found. The concentration of TNF-alpha was significantly 
      higher in OA joints than in healthy joints (p = 0.0019), but TNF-alpha was detected 
      in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided 
      no benefit in terms of objective limb use and activity data in dogs with OA in 
      this pilot study. Although the SF concentration of TNF-alpha was significantly higher 
      in OA joints, few OA joints had measurable TNF-alpha. Collectively, the data indicate 
      TNF-alpha may not be a good therapeutic target in canine OA.
CI  - Copyright (c) 2022 Nakanishi, Lascelles, Allen, Case, Gearing and Enomoto.
FAU - Nakanishi, Aoi
AU  - Nakanishi A
AD  - Department of Animal Science, College of Agriculture and Life Sciences, North 
      Carolina State University, Raleigh, NC, United States.
AD  - Translational Research in Pain (TRiP) Program, Department of Clinical Sciences, 
      College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 
      United States.
FAU - Lascelles, B Duncan X
AU  - Lascelles BDX
AD  - Translational Research in Pain (TRiP) Program, Department of Clinical Sciences, 
      College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 
      United States.
AD  - Department of Clinical Sciences, Comparative Pain Research and Education Center, 
      North Carolina State University, Raleigh, NC, United States.
AD  - Thurston Arthritis Center, UNC School of Medicine, Chapel Hill, NC, United 
      States.
AD  - Center for Translational Pain Research, Department of Anesthesiology, Duke 
      University, Durham, NC, United States.
FAU - Allen, Julie
AU  - Allen J
AD  - Department of Population Health and Pathobiology, North Carolina State 
      University, Raleigh, NC, United States.
FAU - Case, Beth
AU  - Case B
AD  - Translational Research in Pain (TRiP) Program, Department of Clinical Sciences, 
      College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 
      United States.
FAU - Gearing, David
AU  - Gearing D
AD  - The Centre for Innate Immunity and Infectious Diseases, Hudson Institute, 
      Melbourne, VIC, Australia.
FAU - Enomoto, Masataka
AU  - Enomoto M
AD  - Translational Research in Pain (TRiP) Program, Department of Clinical Sciences, 
      College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 
      United States.
LA  - eng
PT  - Journal Article
DEP - 20220602
PL  - Switzerland
TA  - Front Vet Sci
JT  - Frontiers in veterinary science
JID - 101666658
PMC - PMC9201515
OTO - NOTNLM
OT  - TNF-alpha
OT  - force plate
OT  - joint pain
OT  - limb use asymmetry test
OT  - osteoarthritis
COIS- BDXL was a paid consultant for Nexvet and DG was a paid employee of Nexvet. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/21 06:00
MHDA- 2022/06/21 06:01
PMCR- 2022/01/01
CRDT- 2022/06/20 03:47
PHST- 2021/12/15 00:00 [received]
PHST- 2022/04/22 00:00 [accepted]
PHST- 2022/06/20 03:47 [entrez]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2022/06/21 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fvets.2022.836709 [doi]
PST - epublish
SO  - Front Vet Sci. 2022 Jun 2;9:836709. doi: 10.3389/fvets.2022.836709. eCollection 
      2022.