TY - JOUR
T1 - Dual Blockade of TNF and IL-17A Inhibits Inflammation and Structural Damage in a Rat Model of Spondyloarthritis
AU - Hammoura, Ihsan
AU - Fiechter, Renee H.
AU - Bryant, Shaughn H.
AU - Westmoreland, Susan
AU - Kingsbury, Gillian
AU - Waegell, Wendy
AU - Tas, Sander W.
AU - Baeten, Dominique L.
AU - van de Sande, Marleen G. H.
AU - van Tok, Melissa N.
AU - van Duivenvoorde, Leonie M.
N1 - Funding Information: Funding: This research was funded by AbbVie (United States) agreement No C98316. I.H is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847551 (ARCAID). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - The tumor necrosis factor (TNF) and IL-23/IL-17 axes are the main therapeutic targets in spondyloarthritis. Despite the clinical efficacy of blocking either pathway, monotherapy does not induce remission in all patients and its effect on new bone formation remains unclear. We aimed to study the effect of TNF and IL-17A dual inhibition on clinical disease and structural damage using the HLA-B27/human β2-microglobulin transgenic rat model of SpA. Immunized rats were randomized according to arthritis severity, 1 week after arthritis incidence reached 50%, to be treated twice weekly for a period of 5 weeks with either a dual blockade therapy of an anti-TNF antibody and an anti-IL-17A antibody, a single therapy of either antibody, or PBS as vehicle control. Treatment-blinded observers assessed inflammation and structural damage clinically, histologically and by micro-CT imaging. Both single therapies as well as TNF and IL-17A dual blockade therapy reduced clinical spondylitis and peripheral arthritis effectively and similarly. Clinical improvement was confirmed for all treatments by a reduction of histological inflammation and pannus formation (p < 0.05) at the caudal spine. All treatments showed an improvement of structural changes at the axial and peripheral joints on micro-CT imaging, with a significant decrease for roughness (p < 0.05), which reflects both erosion and new bone formation, at the level of the caudal spine. The effect of dual blockade therapy on new bone formation was more prominent at the axial than the peripheral level. Collectively, our study showed that dual blockade therapy significantly reduces inflammation and structural changes, including new bone formation. However, we could not confirm a more pronounced effect of dual inhibition compared to single inhibition.
AB - The tumor necrosis factor (TNF) and IL-23/IL-17 axes are the main therapeutic targets in spondyloarthritis. Despite the clinical efficacy of blocking either pathway, monotherapy does not induce remission in all patients and its effect on new bone formation remains unclear. We aimed to study the effect of TNF and IL-17A dual inhibition on clinical disease and structural damage using the HLA-B27/human β2-microglobulin transgenic rat model of SpA. Immunized rats were randomized according to arthritis severity, 1 week after arthritis incidence reached 50%, to be treated twice weekly for a period of 5 weeks with either a dual blockade therapy of an anti-TNF antibody and an anti-IL-17A antibody, a single therapy of either antibody, or PBS as vehicle control. Treatment-blinded observers assessed inflammation and structural damage clinically, histologically and by micro-CT imaging. Both single therapies as well as TNF and IL-17A dual blockade therapy reduced clinical spondylitis and peripheral arthritis effectively and similarly. Clinical improvement was confirmed for all treatments by a reduction of histological inflammation and pannus formation (p < 0.05) at the caudal spine. All treatments showed an improvement of structural changes at the axial and peripheral joints on micro-CT imaging, with a significant decrease for roughness (p < 0.05), which reflects both erosion and new bone formation, at the level of the caudal spine. The effect of dual blockade therapy on new bone formation was more prominent at the axial than the peripheral level. Collectively, our study showed that dual blockade therapy significantly reduces inflammation and structural changes, including new bone formation. However, we could not confirm a more pronounced effect of dual inhibition compared to single inhibition.
KW - Animal disease model
KW - Anti-IL 17A treatment
KW - Anti-TNF treatment
KW - Dual blockade
KW - New bone formation
KW - Spondyloarthritis
UR - http://www.scopus.com/inward/record.url?scp=85122854225&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms23020859
DO - https://doi.org/10.3390/ijms23020859
M3 - Article
C2 - 35055042
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 2
M1 - 859
ER -