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13-09-2019 | Ankylosing spondylitis | Feature | Article

At a glance: Phase III trials of IL-17A inhibitors in ankylosing spondylitis

Two interleukin (IL)-17A inhibitors are currently approved by the US FDA for the treatment of ankylosing spondylitis (AS): secukinumab and ixekizumab. The approval of secukinumab was based on four phase III, double-blind, randomized controlled trials, MEASURE 1–4, while the approval of ixekizumab followed positive results from the phase III COAST-V and COAST-W trials.

Here, medwireNews summarizes these phase III trials that supported the approval of secukinumab and ixekizumab for AS.

Secukinumab


MEASURE 1

Patient population

Treatment groups

Status

Active AS despite treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), conventional DMARDs, and/or tumor necrosis factor (TNF) inhibitors

Subcutaneous secukinumab 150 mg or 75 mg every 4 weeks following an intravenous loading dose of 10 mg/kg at weeks 0, 2, and 4, or placebo

Published

https://clinicaltrials.gov/ct2/show/NCT01358175

The MEASURE 1 results, published in The New England Journal of Medicine in 2015, demonstrated that ASAS20 response rates at week 16 were significantly higher among participants treated with secukinumab 150 mg or 75 mg versus placebo, at 61% and 60% versus 29%. These improvements were maintained at the 1-year follow-up. The investigators found that the safety profile of secukinumab in MEASURE 1 was consistent with previous studies, with higher rates of infections, including candidiasis, among participants treated with secukinumab versus placebo.

MEASURE 2

Patient population

Treatment groups

Status

Active AS despite treatment with NSAIDs, conventional DMARDs, and/or TNF inhibitors

Subcutaneous secukinumab 150 mg or 75 mg every 4 weeks following a subcutaneous loading dose of 150 or 75 mg at weeks 1, 2, and 3, or placebo

Published

https://clinicaltrials.gov/ct2/show/NCT01649375

The MEASURE 2 findings were published together with MEASURE 1 in The New England Journal of Medicine. In accordance with the MEASURE 1 results, participants in the secukinumab 150 mg and 75 mg groups were significantly more likely to achieve an ASAS20 response at week 16 than those given placebo, with rates of 61% and 41% versus 28%, and these improvements were sustained at the 1-year follow-up.

MEASURE 3

Patient population

Treatment groups

Status

Moderate-to-severe AS despite treatment with NSAIDs, conventional DMARDs, and/or TNF inhibitors

Subcutaneous secukinumab 300 mg or 150 mg every 4 weeks following an intravenous loading dose of 10 mg/kg at weeks 2 and 4, or placebo

Published

https://clinicaltrials.gov/ct2/show/NCT02008916

MEASURE 3 included a higher secukinumab dose (300 mg every 4 weeks) that was not tested in the MEASURE 1 and 2 trials. The investigators demonstrated that patients treated with secukinumab 300 mg or 150 mg every 4 weeks had significantly greater ASAS20 response rates at week 16 than those given placebo (60.5 and 58.1 vs 36.8%), and the improvements were maintained at the 1-year follow-up. The results were reported in Arthritis Research & Therapy in 2017.

Related news story: Further evidence for the benefits of secukinumab in AS patients

MEASURE 4

Patient population

Treatment groups

Status

Moderate-to-severe AS despite treatment with NSAIDs, conventional DMARDs, and/or TNF inhibitors

Subcutaneous secukinumab 150 mg every 4 weeks, with or without a 150 mg once weekly subcutaneous loading dose between baseline and week 4, or placebo

Published

https://clinicaltrials.gov/ct2/show/study/NCT02159053

This trial evaluated the 150 mg dose of secukinumab with and without a loading dose. As reported in Rheumatology & Therapy in 2018, ASAS20 response rates at week 16 were numerically higher among patients treated with secukinumab 150 mg every 4 weeks with or without a loading dose versus placebo (59.5 and 61.5 vs 47.0%). The differences between the groups did not reach statistical significance, which the investigators attribute to higher than expected response rates in the placebo group.

Ixekizumab


COAST-V

Patient population

Treatment groups

Status

Biologic-naïve AS patients with an inadequate response to NSAIDs

Subcutaneous ixekizumab 80 mg every 2 or 4 weeks, adalimumab 40 mg every 2 weeks, or placebo

Published

https://clinicaltrials.gov/ct2/show/NCT02696785

As reported in The Lancet in 2018, ASAS40 response rates at week 16 were significantly higher among patients treated with ixekizumab 80 mg every 2 weeks or every 4 weeks relative to placebo, at 52% and 48% versus 18%. A total of 36% of adalimumab-treated patients achieved an ASAS40 response at week 16. There were no new or unexpected safety findings with the IL-17A inhibitor.

Related news story: COAST-V results support ixekizumab for the treatment of ankylosing spondylitis

COAST-W

Patient population

Treatment groups

Status

AS patients with an inadequate response to TNF inhibitors

Subcutaneous ixekizumab 80 mg every 2 weeks or every 4 weeks (following a loading dose of 80 mg or 160 mg), or placebo

Published

https://clinicaltrials.gov/ct2/show/NCT02696798

COAST-W investigated ixekizumab as a treatment option for patients with an inadequate response or intolerance to prior treatment with one or two TNF inhibitors. The results were in line with those from COAST-V, demonstrating significantly higher ASAS40 response rates at week 16 among patients given ixekizumab every 2 weeks or every 4 weeks versus placebo (30.6 and 25.4 vs 12.5%). The COAST-W results were published in Arthritis & Rheumatology in 2018.

Related news story: Further evidence for the benefits of ixekizumab in ankylosing spondylitis

By Claire Barnard

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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