Ixekizumab delivers rapid improvements in active radiographic axial spondyloarthritis
Ixekizumab is safe and effective in the treatment of patients with active radiographic axial spondyloarthritis (r‐axSpA) and previously inadequate response or intolerance to tumour necrosis factor inhibitors (TNFIs), producing rapid and significant improvements in the signs and symptoms, according to the 16-week results of the phase III COAST-W trial.
“The current results support ixekizumab as a treatment option in patients with r-axSpA and prior inadequate response or intolerance to TNFI,” the authors said.
COAST-W randomized 316 patients to receive placebo (n=104) or 80‐mg subcutaneous ixekizumab every 2 (IXEQ2W; n=98) or 4 (IXEQ4W; n=114) weeks, with the starting dose being 80 or 160 mg. Significantly more patients in the two ixekizumab arms achieved the primary endpoint of ASAS40 response (Assessment of SpondyloArthritis International Society 40 percent) at week 16 (30.6 percent and 25.4 percent vs 12.5 percent; p=0.003 or p=0.017, respectively). [Arthritis Rheumatol 2018;doi:10.1002/art.40753]
The response with ixekizumab was seen as early as the first week of treatment, the authors noted.
“Despite the greater exposure with the IXEQ2W regimen, IXEQ2W did not show a clinically meaningful incremental increase in observed efficacy relative to the IXEQ4W regimen. Similarly, the week 0 starting dose of 160 mg did not reveal a clinically meaningful incremental improvement in week 16 response rates relative to the 80-mg starting dose for either ixekizumab regimen,” they added.
Aside from response, other endpoints such as disease activity, function, quality of life and spinal magnetic resonance imaging (MRI) inflammation showed superior improvements with both ixekizumab regimens vs placebo.
The drug showed an acceptable safety profile in the present patient population with longstanding and very active disease. Treatment-emergent adverse events (AEs) occurred more frequently with ixekizumab than with placebo, driven by upper respiratory tract infections and injection site reactions. Serious AEs occurred at similar rates across ixekizumab and placebo arms.
“COAST-W is the first placebo-controlled trial to generate spinal MRI data in a TNFI intolerant or inadequate responder population,” the authors pointed out. “Despite baseline levels of spinal inflammation being relatively low, thereby hampering ability to improve, a statistically significant and objective effect on spinal inflammation was observed for IXEQ2W and IXEQ4W … which was supported by parallel improvements in CRP.”
“Conversely, the current dataset is limited to a 16-week treatment period. Longer-term data, which are being collected through 1 year of treatment in the present trial, as well as during an optional 2-year extension trial, will further inform on the long-term efficacy and safety of ixekizumab,” they added.