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

Updated: Sep 03, 2019
  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin 17A (IL-17A). IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab was approved by the FDA for adults with active AS in January 2016.

Approval of secukinumab for AS was based on 2 phase 3 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. [123]

Ixekizumab (Taltz) also targets IL-17A. In August 2019, it was approved by the FDA for adults with active AS. Approval was based on two phase 3 trials (COAST-V and COAST-W) that included 657 adults with active AS. In COAST-V, patients who had not been treated with biological DMARDs were randomized to ixekizumab 80 mg SC every 2 or 4 weeks, adalimumab 40 mg every 2 weeks, or placebo. At week 16, compared with placebo (16 [18%] of 87), more patients achieved improvement with ixekizumab every 2 weeks (43 [52%] of 83; P< 0.0001), ixekizumab every 4 weeks (39 [48%] of 81; P < 0.0001), and adalimumab (32 [36%] of 90; P = 0.0053). [124]

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. Results showed ixekizumab 80 mg every 2 weeks (30.6%; p = 0.003) and 80 mg every 4 weeks plus initial 160 mg dose (25.4; p = 0.017) respectively showed improvement in AS signs and symptoms compared with placebo (12.5%). [125]


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