van der Heijde D, et al. - In patients with radiographic axial spondyloarthritis not previously treated with biological disease-modifying anti-rheumatic drugs (bDMARDs), researchers assessed the effectiveness and safety of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A). For improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs, the superiority of each tested dosing regimen of ixekizumab vs placebo was noted. They noted a consistent safety profile with previous indications of ixekizumab.

Methods

• Authors conducted a phase 3, randomized, double-blind, placebo-controlled superiority study of ixekizumab in which they recruited adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria from 84 sites (12 countries) in Europe, Asia, and North America.
• They randomly assigned the patients (1:1:1:1), by use of a computer-generated random sequence, to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo.
• Comparing the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups vs the placebo group was the primary objective.
• They included the adalimumab reference group as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results.

Results

• AS per data, 341 patients were randomly assigned between June 20, 2016, and August 22, 2017 to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81).
• At week 16, more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p < 0·0001), ixekizumab Q4W (39 [48%] of 81; p < 0·0001), and adalimumab (32 [36%] of 90; p=0·0053) than with placebo (16 [18%] of 87).
• In each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups, 1 serious infection occurred; none were reported with placebo.
• Findings suggested that 1 (1%) Candida infection occurred in the adalimumab group and 1 (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease.
• Results did not demonstrate any treatment-emergent opportunistic infections, malignancies, or deaths.