What is the role of interleukin inhibitors in the treatment of ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA)?

Updated: Feb 02, 2021
  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Interleukin 17A (IL-17A) is a proinflammatory cytokine that is involved in normal inflammatory and immune responses and also plays a key role in the pathogenesis of AS. Two human IgG monoclonal antibodies that target IL-17A are approved for use in AS and active non-radiographic axial spondyloarthritis: secukinumab and ixekizumab.

Secukinumab

Secukinumab (Cosentyx), a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, was approved by the FDA for adults with active AS in January 2016. In June 2020, approval was expanded to include non-radiographic axial spondyloarthritis (nr-axSpA).

Approval of secukinumab for AS was based on 2 phase III trials (MEASURE 1 and 2). In MEASURE 1 (n=371), the Assessment of Spondyloarthritis International Society (ASAS20) response rates at week 16 were 61%, 60%, and 29% for secukinumab doses of 150 mg and 75 mg subcutaneously and for placebo, respectively (P < 0.001 for both comparisons with placebo). In MEASURE 2 (n=219), the rates were 61%, 41%, and 28% for secukinumab doses of 150 mg and 75 mg and for placebo, respectively (P < 0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. [129]

The approval of secukinumab for nr-axSpA was based on outcomes from the PREVENT phase III study (n = 555) in adults with active nr-axSpA who were biologic-treatment naïve or had an inadequate response or intolerance to an anti–TNF-α therapy. Of the 481 patients who completed 52 weeks of treatment, ASAS40 in TNFi-naïve patients was significantly higher with a loading dose (41.5%) at week 16 and without a loading dose (39.8%) at week 52 compared with placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). [105]

Ixekizumab 

Ixekizumab (Taltz), a humanized monoclonal IgG4 antibody, also targets IL-17A. In August 2019, ixekizumab was approved by the FDA for adults with active AS. In June 2020, approval was expanded to include nr-axSpA. Approval was based on two phase III trials (COAST-V and COAST-W) that included 657 adults with active AS. In COAST-V, which included patients who had not been treated with biological DMARDs, at week 16, significantly more patients achieved improvement with ixekizumab than with placebo or adalimumab. [130]  In the COAST-W trial, patients with active AS with a previous inadequate response or intolerance to TNF inhibitors showed a statistical improvement at 16 weeks with ixekizumab, compared with placebo (30.6% versus 12.5%; P=0.003%). [131]

Approval of ixekizumab for active nr-axSpA with objective signs of inflammation was based on the COAST-X phase III trial. The primary endpoint,  the proportion of patients achieving ASAS40 at 52 weeks, was achieved in 30% of patients treated with ixekizumab versus 13% for placebo (P = 0.0045). [106]


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