Anti-Il-17a Treatment Blocks Inflammation, Destruction And New Bone Formation In Experimental Spondyloarthritis In Hla-B27 Transgenic Rats

Background The IL-17 axis has been identified as a crucial pathophysiological pathway in spondyloarthritis (SpA). This concept was recently validated by phase II and III clinical trials with secukinumab (anti-IL17A), brodalumab (anti-IL17RA), and ustekinumab (anti-IL23/IL12p40) in ankylosing spondylitis and psoriatic arthritis. Targeting the IL-17 axis significantly suppressed inflammation and halted bone and cartilage destruction in these trials. The potential impact of IL-17A inhibition on new bone formation, the major form of structural damage in SpA, remains unknown. Assessment of this feature in SpA requires large patient numbers treated for an extended period and appropriate control groups. Therefore, we aimed to assess the impact of anti-IL17A on new bone formation in a validated animal model of SpA. Methods 6 weeks old, orchiectomized, HLA-B27/huβ2m tg rats were immunized with 45 μg heat-inactivated M. tuberculosis in IFA. One week after immunization, rats (n=6/group) were treated weekly with an anti-mouse/rat IL-17A antibody or an IgG2a isotype control at 15mg/kg i.p. Clinical measurements included weight, clinical scores for spondylitis and arthritis, and hind limb swelling measured by plethysmometry. After 6 weeks, rats were sacrificed for skeletal analysis by micor-CT imaging and histology. Results Control animals failed to gain weight over time, whereas anti-IL-17A-treated rats showed a significant increase in weight compared to baseline (102% versus 134%; p Conclusions IL-17A blockade significantly suppressed spondylitis and arthritis in the M. tub -induced disease B27 tg rat model of SpA. Moreover, micro-CT data indicated that IL-17A blockade also impacts structural damage, including pathological new bone formation. Disclosure of Interest None declared