Meeting News

COAST-V: Taltz improves ankylosing spondylitis symptoms

CHICAGO — Ixekizumab was superior to placebo in reducing disease activity while improving function, as well as spinal and sacroiliac joint inflammation among patients with ankylosing spondylitis, according to phase 3 data from the COAST-V trial.

During a presentation at the ACR/ARHP 2018 Annual Meeting, Désirée van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center in the Netherlands, said COAST-V is the first phase 3 study to evaluate ixekizumab (Taltz, Eli Lilly and Company) in patients with active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA), who have not previously received treatment with biologic disease-modifying anti-rheumatic drugs (bDMARDs). The findings were also published in The Lancet.

“We know that biologics are recommended for the treatment of AS if conventional treatment with NSAIDs fails,” Heijde said. “Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is already approved for the treatment of psoriasis and psoriatic arthritis.”

For the study, van der Heijde and colleagues randomly assigned 341 patients with AS to receive:

  • 80 mg of ixekizumab subcutaneously every 4 weeks (after an 80 mg or 160 mg loading dose);
  • 80 mg of ixekizumab subcutaneously every 2 weeks (after an 80 mg or 160 mg loading dose);
  • 40 mg of adalimumab subcutaneously every 2 weeks; or
  • subcutaneous placebo.

The primary endpoint was the proportion of patients who received a 40% Assessment in SpondyloArthritis International Society (ASAS40) response by week 16. Secondary endpoints included ASAS20 response, a 50% or greater improvement in the Bath ankylosing spondylitis disease activity index (BASDAI50), as well as changes in AS disease activity score (ASDAS), Bath ankylosing spondylitis function index (BASFI), MRI spine SpA Research Consortium of Canada (SPARCC) score, sacroiliac joint SPARCC score, and ASAS-Health Index (HI).

At week 16, 48% of patients who received ixekizumab every 4 weeks and 52% who received ixekizumab every 2 weeks achieved ASAS40 vs. 36% of patients who received adalimumab and 18% who received placebo.

Patients in the ixekizumab arm also had significantly greater improvements for all secondary endpoints compared with those in the placebo arm. Among patients who received ixekizumab every 4 weeks, 64% achieved ASAS20 and 42% achieved BASDAI50. They also averaged a 1.4-point reduction in ASDAS, 2.4-point reduction in BASFI, 11.0-point reduction in spine SPARCC score, 4.0-point reduction in sacroiliac joint SPARCC score, and 2.4-point reduction in ASAS-HI. Among patients who received ixekizumab every 2 weeks, 69% achieved ASAS20 and 43% achieved BASDAI50. They also averaged a 1.4-point reduction in ASDAS, 2.4-point reduction in BASFI, 9.6-point reduction in spine SPARCC score, 4.3-point reduction in sacroiliac joint SPARCC score and 2.7-point reduction in ASAS-HI.

In comparison, 59% of patients who received adalimumab achieved ASAS20 and 32% achieved BASDAI50. They averaged a 1.3-point reduction in ASDAS, 2.1-point reduction in BASFI, 11.6-point reduction in spine SPARCC score, 4.2-point reduction in sacroiliac joint SPARCC score and 2.3-point reduction in ASAS-HI. Meanwhile, only 40% of patients who received placebo achieved ASAS20 and 17% achieved BASDAI50. van der Heijde said there was almost no change in other endpoints, including ASDAS (average 0.5-point reduction), BASFI (1.2-point reduction), spine SPARCC score (1.5-point reduction), sacroiliac joint SPARCC score (0.9-point reduction) and ASAS-HI (1.3-point reduction).

“An early onset of efficacy was demonstrated with a significant difference between the ixekizumab arms and placebo as early as week 1 for ASAS20 and week 2 for ASAS40,” she said.

In a safety analysis, ixekizumab “showed no unexpected safety findings,” according to van der Heijde. Treatment-emergent adverse events occurred in 42% of patients who received ixekizumab every 4 weeks, 43.4% among those who received ixekizumab every 2 weeks, 48.9% among those who received adalimumab and 39.5% who received placebo. Only one patient in the adalimumab group discontinued treatment due to an adverse event, which was an injection site reaction. Three patients who received ixekizumab every 2 weeks discontinued treatment due to injection site reactions (n = 2) and diarrhea (n = 1).

Of note, there was one serious infection reported in each of the active treatment groups, including one Candida infection in the adalimumab group.

van der Heijde said the trial will continue until week 52.

Ixekizumab also demonstrated a statistically significant improvement in AS signs and symptoms compared with placebo during the phase 3 COAST-W trial, which is another randomized, double-blind 16-week study. Both COAST-V and COAST-W trials are part of a clinical development program assessing ixekizumab across various subset populations of patients with AS. Eli Lilly and Company announced plans in a press release to submit an application for ixekizumab as a treatment for AS/r-axSpA later this year. – by Stephanie Viguers

References:

van der Heijde D, et al. Abstract 1864. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

van der Heijde, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31946-9.

Disclosures: van der Heijde reports being a consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma.

CHICAGO — Ixekizumab was superior to placebo in reducing disease activity while improving function, as well as spinal and sacroiliac joint inflammation among patients with ankylosing spondylitis, according to phase 3 data from the COAST-V trial.

During a presentation at the ACR/ARHP 2018 Annual Meeting, Désirée van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center in the Netherlands, said COAST-V is the first phase 3 study to evaluate ixekizumab (Taltz, Eli Lilly and Company) in patients with active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA), who have not previously received treatment with biologic disease-modifying anti-rheumatic drugs (bDMARDs). The findings were also published in The Lancet.

“We know that biologics are recommended for the treatment of AS if conventional treatment with NSAIDs fails,” Heijde said. “Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is already approved for the treatment of psoriasis and psoriatic arthritis.”

For the study, van der Heijde and colleagues randomly assigned 341 patients with AS to receive:

  • 80 mg of ixekizumab subcutaneously every 4 weeks (after an 80 mg or 160 mg loading dose);
  • 80 mg of ixekizumab subcutaneously every 2 weeks (after an 80 mg or 160 mg loading dose);
  • 40 mg of adalimumab subcutaneously every 2 weeks; or
  • subcutaneous placebo.

The primary endpoint was the proportion of patients who received a 40% Assessment in SpondyloArthritis International Society (ASAS40) response by week 16. Secondary endpoints included ASAS20 response, a 50% or greater improvement in the Bath ankylosing spondylitis disease activity index (BASDAI50), as well as changes in AS disease activity score (ASDAS), Bath ankylosing spondylitis function index (BASFI), MRI spine SpA Research Consortium of Canada (SPARCC) score, sacroiliac joint SPARCC score, and ASAS-Health Index (HI).

At week 16, 48% of patients who received ixekizumab every 4 weeks and 52% who received ixekizumab every 2 weeks achieved ASAS40 vs. 36% of patients who received adalimumab and 18% who received placebo.

Patients in the ixekizumab arm also had significantly greater improvements for all secondary endpoints compared with those in the placebo arm. Among patients who received ixekizumab every 4 weeks, 64% achieved ASAS20 and 42% achieved BASDAI50. They also averaged a 1.4-point reduction in ASDAS, 2.4-point reduction in BASFI, 11.0-point reduction in spine SPARCC score, 4.0-point reduction in sacroiliac joint SPARCC score, and 2.4-point reduction in ASAS-HI. Among patients who received ixekizumab every 2 weeks, 69% achieved ASAS20 and 43% achieved BASDAI50. They also averaged a 1.4-point reduction in ASDAS, 2.4-point reduction in BASFI, 9.6-point reduction in spine SPARCC score, 4.3-point reduction in sacroiliac joint SPARCC score and 2.7-point reduction in ASAS-HI.

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In comparison, 59% of patients who received adalimumab achieved ASAS20 and 32% achieved BASDAI50. They averaged a 1.3-point reduction in ASDAS, 2.1-point reduction in BASFI, 11.6-point reduction in spine SPARCC score, 4.2-point reduction in sacroiliac joint SPARCC score and 2.3-point reduction in ASAS-HI. Meanwhile, only 40% of patients who received placebo achieved ASAS20 and 17% achieved BASDAI50. van der Heijde said there was almost no change in other endpoints, including ASDAS (average 0.5-point reduction), BASFI (1.2-point reduction), spine SPARCC score (1.5-point reduction), sacroiliac joint SPARCC score (0.9-point reduction) and ASAS-HI (1.3-point reduction).

“An early onset of efficacy was demonstrated with a significant difference between the ixekizumab arms and placebo as early as week 1 for ASAS20 and week 2 for ASAS40,” she said.

In a safety analysis, ixekizumab “showed no unexpected safety findings,” according to van der Heijde. Treatment-emergent adverse events occurred in 42% of patients who received ixekizumab every 4 weeks, 43.4% among those who received ixekizumab every 2 weeks, 48.9% among those who received adalimumab and 39.5% who received placebo. Only one patient in the adalimumab group discontinued treatment due to an adverse event, which was an injection site reaction. Three patients who received ixekizumab every 2 weeks discontinued treatment due to injection site reactions (n = 2) and diarrhea (n = 1).

Of note, there was one serious infection reported in each of the active treatment groups, including one Candida infection in the adalimumab group.

van der Heijde said the trial will continue until week 52.

Ixekizumab also demonstrated a statistically significant improvement in AS signs and symptoms compared with placebo during the phase 3 COAST-W trial, which is another randomized, double-blind 16-week study. Both COAST-V and COAST-W trials are part of a clinical development program assessing ixekizumab across various subset populations of patients with AS. Eli Lilly and Company announced plans in a press release to submit an application for ixekizumab as a treatment for AS/r-axSpA later this year. – by Stephanie Viguers

References:

van der Heijde D, et al. Abstract 1864. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

van der Heijde, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31946-9.

Disclosures: van der Heijde reports being a consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma.

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