Background/Purpose: Secukinumab, a monocloncal antibody to IL-17A, suppresses signs and symptoms as well as inflammation in ankylosing spondylitis and psoriatic arthritis, and inhibits bone and cartilage destruction in psoriatic arthritis. As to new bone formation, a distinct form of structural damage in spondyloarthritis (SpA), a 2-years Secukinumab study in AS showed that mean progression of new bone formation was low (0.3 mSASSS points) and that 80% of patients did not show any progression at all (Baraliakos X. et al [abstract] Arthritis Rheum 2015; 67 suppl 10). As formal demonstration of an effect of anti-IL17A on new bone formation in human SpA requires long term data and the inclusion of an appropriate control group, we aimed to assess the potential impact of anti-IL17A on new bone formation in a validated animal model of SpA.

Methods: SpA-like arthritis and spondylitis was induced in HLA-B27/huβ2m tg rats (23-1×283-2) by immunization with low dose heat-inactivated M. tuberculosis/IFA. The animals were treated with 15 mg/kg anti-mouse/rat IL-17A antibody versus IgG2a isotype control weekly or, alternatively, with 10 mg/kg anti-TNF (Etanercept) versus PBS twice weekly in both prophylactic and therapeutic experiments for a period of 5 weeks. Arthritis and spondylitis were scored clinically and hind paw swelling was measured by plethysmometry. At the end of the study rats were sacrificed for skeletal analysis by micro-CT (low density bone volume as a measure for new bone formation) and histology.

Results:  Prophylactic treatment with anti-IL-17A or anti-TNF showed a significant delay in arthritis and spondylitis when compared to their control groups. In addition, arthritis was significantly less severe in the anti-IL-17A or anti-TNF treatment groups as assessed by clinical scoring as well as by hind paw swelling. Therapeutic treatment with anti-IL-17A showed a significant reduction in arthritis score and hind paw swelling compared to the control group, spondylitis incidence remained stable after treatment. In contrast, treatment with anti-TNF in a therapeutic setting did not affect arthritis severity and spondylitis incidence continued to increase over time. Micro-CT analysis after therapeutic treatment revealed low density/newly formed bone present in both control groups. Treatment with anti-IL-17A significantly reduced levels of low density bone in the ankle joints, when compared to the IgG2a treated controls, and were even comparable to healthy age matched HLA-B27/huβ2m tg rats. In the axial joints new bone formation was present in 11 vertebrae from 5/9 control rats and 9 vertebrae from 3/9 anti-IL-17A treated rats. Coloring by bone density suggests less new bone formation in the anti-IL-17A treated group. In contrast, therapeutic treatment with anti-TNF did not affect new bone formation in both peripheral and axial joints.

Conclusion:  These data show that, although the model is dependent on both IL-17A and TNF, only blockade of IL-17A affects clinical symptoms in a therapeutic setting. Strikingly, micro-CT analysis indicates that anti-IL-17A but not anti-TNF can halt pathological new bone formation in a therapeutic treatment setting.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-il-17a-but-not-anti-tnf-can-halt-pathological-new-bone-formation-in-experimental-spondyloarthritis/