Ixekizumab (IXE) is a high affinity IL-17A monoclonal antibody that has previously shown efficacy in AS/radiographic-axial spondyloarthritis (r-axSpA). [1,2] COAST-X (NCT02757352) is a phase 3 study that assessed efficacy and safety of IXE in patients (pts) with active non-radiographic-axial spondyloarthritis (nr-axSpA) and objective signs of inflammation.
COAST-X was a 52-week, randomized, double-blind, placebo (PBO)-controlled study enrolling adults with an established diagnosis of axSpA who met ASAS (but not modified New York) criteria, had BASDAI ≥4, sacroiliitis on magnetic resonance imaging [MRI] or elevated CRP >5 mg/L), and inadequate response or intolerance to NSAIDs.
Patients were randomized 1:1:1 to 80 mg IXE every 4 weeks (Q4W), 80 mg IXE every 2 weeks (Q2W), or PBO.
Changes to conventional background medication (NSAIDs, csDMARDs, analgesics, and low dose corticosteroids) as well as escape to open label (OL) IXE Q2W were allowed at investigator discretion after week 16.
A logistic regression model with non-responder imputation was used for categorical data; a mixed effects model of repeated measures was used for continuous variables; analysis of covariance was used for sacroiliac joint (SIJ) MRI SPARCC (Spondyloarthritis Research Consortium of Canada) scores.
ASAS40 at week 16 (US regulatory endpoint) or week 52.
A total of 303 subjects were randomized: PBO (N=105), IXE Q4W (N=96), IXE Q2W (N=102).
The difference of patients achieving ASAS40 with both IXE regimens vs. PBO was observed as early as week 1.
Significantly more pts in the IXE groups compared to the PBO group achieved ASAS40 at week 16: IXE Q2W (40%), IXE Q4W (35%) vs. PBO (19%, p <0.01) and at week 52: IXE Q2W (31%), IXE Q4W (30%) vs. PBO (13%, p <0.01) (Figure).
Compared to PBO, pts on either IXE regimen had significantly greater changes from baseline at week 16 and week 52 with regard to disease activity, functional status, and SIJ SPARCC scores.
A notable proportion of patients who escaped to OL IXE Q2W had ASAS40 response at the time of escape (16.7%, 25%, and 6.5% on IXE Q2W, IXEQ4W, and PBO, respectively), and ASA40 rates further increased on OL IXE Q2.
The frequency of serious adverse events and adverse events that led to treatment discontinuation was low and similar across all arms; no new safety signal was identified.
Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase iii randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019 Apr;71(4):599-611.
van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018 Dec 8;392(10163):2441-51.
Presenter disclosure: The presenter has reported relationships with Abbvie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Janssen Research & Development, LLC, Novartis, Pfizer, UCB Pharma.