If approved by the U.S. Food and Drug Administration (FDA), difficult-to-treat patients with axial spondyloarthritis who fail or are intolerant to standard treatment with tumor necrosis factor inhibitors (TNFi) may have a new treatment option.
That new option is a high-affinity monoclonal antibody, called ixekizumab, which selectively targets an area linked to the immunopathology of axial spondyloarthritis—specifically, the interleukin (IL) 17 axis. Prior studies have shown the efficacy of IL-17 inhibition in patients with axial spondyloarthritis. Secukinumab is the first agent in this class to show efficacy in treating patients with this condition.1-3 Most of the secukinumab trials enrolled patients who were exclusively or predominantly disease-modifying anti-rheumatic drug (DMARD) naive. Lacking, however, are data evaluating the efficacy of IL-17 inhibition specifically in patients who fail to respond adequately to, or are intolerant of, TNF inhibitors.
A new study looked at the efficacy and safety of ixekizumab in this setting.
“Ankylosing spondylitis is a chronic and debilitating disease, and I have a large number of patients who have failed TNF inhibitors,” says lead author of the study Atul Deodhar, MD, a professor of medicine and the medical director of the Rheumatology Clinics in the Division of Arthritis & Rheumatic Diseases at the Oregon Health & Science University in Portland. “There’s a need for more options specifically for difficult-to-treat patient populations. This research provides valuable insights into the potential for ixekizumab to become a new treatment option for patients with ankylosing spondylitis,” he says.
Focus on Difficult-to-Treat Patients
Dr. Deodhar
Called the COAST-W trial, the phase 3 randomized controlled trial enrolled 316 patients with active radiographic axial ankylosing spondylitis who had an inadequate response to or were intolerant to one of two TNF inhibitors. Most patients in the study were white men (80%), and most (n=315) had been treated with a prior TNF inhibitor. Of these, 205 (65.1%) had an inadequate response to one TNF inhibitor, 78 (24.8%) had inadequate response to two TNF inhibitors and 32 (10.2%) were intolerant to TNF inhibitors.
Patients were randomized for 16 weeks to one of three treatment groups: placebo (n=114), 80 mg of ixekizumab subcutaneously every two weeks (IXEQ2W) (n=98), or 80 mg of ixekizumab subcutaneously every four weeks (IXEQ4W) (n=114). The starting dose in each treatment group was either 80 mg or 160 mg.
The primary outcome of the study was an Assessment in SpondyloArthritis International Society 40% response (ASAS40), representing at least a 40% improvement in signs and symptoms of disease.
As shown in Table 1 (see above), significantly more patients treated at either dose of ixekizumab achieved the study’s primary outcome compared to those treated with placebo.
According to the study authors, a significant response by patients in both treatment groups was observed as early as the first week of treatment.
“This is the first dedicated study to measure the effect of biologic therapy in this patient population, including spinal inflammation, by using magnetic resonance imaging [MRI],” says Dr. Deodhar, who emphasized the importance of using MRI to assess spinal inflammation.
Assessing spinal MRI and systemic inflammation was a secondary outcome of the study. Using the mean change in MRI spine Spondyloarthritis Research Consortium of Canada (SPARCC) scores at baseline and serum mean change from baseline C-reactive protein (CRP) levels at 16 weeks to measure spinal and systemic inflammation, the study found patients treated with ixekizumab had a statistically significant reduction in inflammation seen on spinal MRI compared to placebo (–11.0 in the IXEQ2W group, –9.6 in the IXEQ4W group and –1.5 in the placebo group).
“Patients treated with ixekizumab experienced a statistically significant reduction in inflammation seen on spinal MRI compared to placebo,” he says, emphasizing that the measure used to assess spinal inflammation on MRI is “an objective measure that adds to the subjective measures of symptom relief.”