CHICAGO — Ixekizumab significantly improved the signs and symptoms of ankylosing spondylitis in patients who previously did not respond to or tolerate TNF inhibitors, according to phase 3 data from the COAST-W trial.
At the ACR/ARHP 2018 Annual Meeting, Atul A. Deodhar, MD, professor of medicine and medical director at the Oregon Health and Science University, reported that TNF inhibitors are recommended for patients with AS, also known as radiographic axial spondyloarthritis, who have inadequate responses or intolerance to NSAIDs. Some of these patients, however, also do not respond to or tolerate TNF inhibitors. According to Deodhar, COAST-W is the first clinical trial to exclusively focus on this difficult-to-treat population.
For the trial, Deodhar and colleagues randomly assigned 316 patients with AS and prior inadequate response (90%) or intolerance (10%) to one or two TNF inhibitors to receive 80 mg of subcutaneous ixekizumab (Taltz, Eli Lilly and Company) every 2 weeks (Q2W) or 4 weeks (Q4W) following an 80-mg or 160-mg loading dose, or placebo. The primary endpoint was a 40% Assessment in Spondyloarthritis International Society (ASAS40) response by week 16. The researchers used MRIs to assess for spinal inflammation.
At week 16, 25.4% of patients who received ixekizumab Q4W and 30.6% who received ixekizumab Q2W achieved ASAS40 vs. 12.5% of patients who received placebo. Ixekizumab was also associated with significant improvements in:
- ASAS20, which was achieved by 48.2% of patients who received ixekizumab Q4W and 46.9% who received ixekizumab Q2W vs. 29.8% who received placebo;
- Bath AS Disease Activity Index (BASDAI), which was reduced by 2.2 points among patients who received ixekizumab Q4W and 2.1 points among patients who received ixekizumab Q2W vs. 0.9 points among patients who received placebo; and
- MRI spine SpA Research Consortium of Canada (SPARCC) score, which was reduced by 3 points among patients who received ixekizumab Q4W and 4 points among patients who received ixekizumab Q2W vs. a 3-point increase among patients who received placebo.
Treatment-related adverse events occurred in 64% of patients who received ixekizumab Q4W, 60.2% of those who received ixekizumab Q2W and 49% who received placebo. Most treatment-related adverse events were mild or moderate. There was no significant difference in the incidence of serious adverse events in the ixekizumab Q4W group (3.5%), ixekizumab Q2W group (3.1%) and placebo group (4.8%). Eight patients in the ixekizumab Q4W group, three in the ixekizumab Q2W group and two in the placebo group discontinued treatment due to adverse events. No deaths related to the study drug were reported.
Additional findings from the COAST-V trial, which were also presented at the ACR/ARHP 2018 Annual Meeting, showed that ixekizumab was superior to placebo in reducing disease activity while improving function, as well as spinal and sacroiliac joint inflammation among patients with AS. Based on the positive findings of both COAST-W and COAST-V trials, Eli Lilly and Company announced in a press release that the company plans on submitting an application to the FDA later this year for the approval of ixekizumab as a treatment for AS. – by Stephanie Viguers
Deodhar AA, et al. Abstract L20. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.
Disclosure: Deodhar reports receiving grant/research support and/or consulting fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma.