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Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model

Katri, Anna; Dąbrowska, Aneta ; Löfvall, Henrik LU ; Ding, Ming; Karsdal, Morten A.; Andreassen, Kim V.; Thudium, Christian S. and Henriksen, Kim (2019) In Arthritis Research & Therapy 21(1).
Abstract (Swedish)
Background: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.
Methods: Collagen-induced arthritis (CIA) was induced in 40... (More)
Background: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.
Methods: Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.
Results: Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.
Conclusions: This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure. (Less)
Abstract
Background: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.
Methods: Collagen-induced arthritis (CIA) was induced in 40... (More)
Background: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.
Methods: Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.
Results: Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.
Conclusions: This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arthritis, DACRA, Arthritis, Rheumatoid/drug therapy
in
Arthritis Research & Therapy
volume
21
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85062011970
ISSN
1478-6362
DOI
10.1186/s13075-019-1819-9
language
English
LU publication?
yes
id
837f3e04-2594-4d79-aa7d-4139b5dfadbb
date added to LUP
2019-02-28 11:49:51
date last changed
2019-04-23 04:46:14
@article{837f3e04-2594-4d79-aa7d-4139b5dfadbb,
  abstract     = {Background: Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.<br/>Methods: Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.<br/>Results: Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.<br/>Conclusions: This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.},
  articleno    = {68},
  author       = {Katri, Anna and Dąbrowska, Aneta  and Löfvall, Henrik and Ding, Ming and Karsdal, Morten A. and Andreassen, Kim V. and Thudium, Christian S. and Henriksen, Kim},
  issn         = {1478-6362},
  keyword      = {Arthritis,DACRA,Arthritis, Rheumatoid/drug therapy},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Arthritis Research & Therapy},
  title        = {Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model},
  url          = {http://dx.doi.org/10.1186/s13075-019-1819-9},
  volume       = {21},
  year         = {2019},
}