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Background: Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X.Methods: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0-10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov, number NCT02757352.Findings: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified.Interpretation: Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy.Funding: Eli Lilly and Company. [ABSTRACT FROM AUTHOR]

Background: Recognition, diagnosis, and management of axial spondyloarthritis (axial SpA) continue to advance., Objectives: The objectives of this study were to compare referrals, diagnosis, and management of axial SpA in Western Europe (WE), North America (US and Canada), and the rest of world (RoW) in academic and community rheumatology practices and to identify areas for further education., Methods: Rheumatologists responded online to the MAXIMA (Management of Axial SpA International and Multicentric Approaches) survey. Questions pertained to referral, diagnosis, and management of axial SpA., Results: Rheumatologists (N = 809) from 56 countries completed the survey about patients with chronic back pain (≥3 months) starting before age 45 years. Responses from academic and community practice rheumatologists were generally similar. Most referrals were from primary care providers. Symptom duration of 3 years or more at referral was reported more frequently by WE and RoW than US respondents. More WE and RoW than US rheumatologists referred to the Assessment of SpondyloArthritis International Society criteria for axial SpA in clinical practice. Rheumatologists reported prescribing disease-modifying antirheumatic drugs for the management of axial SpA. Sulfasalazine was frequently prescribed across regions; methotrexate was more commonly prescribed by US rheumatologists compared with other regions., Conclusions: Referral patterns, diagnosis, and disease management for axial SpA were similar among WE, North America, and RoW rheumatologists and in academic/community practices, although more WE and RoW rheumatologists referred to Assessment of SpondyloArthritis International Society criteria in clinical practice. Disease-modifying antirheumatic drugs were commonly prescribed for axial SpA patients, although it was unclear whether these were prescribed for axial or peripheral symptoms.

The Spondyloarthritis Research and Therapy Network (SPARTAN), founded in 2003 to promote research, education, and treatment of ankylosing spondylitis (AS) and related forms of spondyloarthritis (SpA), held its 7th Annual Research and Education Meeting in July 2009 in Houston, Texas. Current controversies in SpA discussed during the meeting included an update on the epidemiology of AS, axial SpA, and inflammatory back pain; the adequacy of the mSASS to assess radiographic involvement; the helpfulness of magnetic resonance imaging in assessing disease progression; the reliability of metrology in assessing damage; and whether biologic agents alter the course of AS. Presentations also were made on psoriasis in the SCID mouse model; the challenges and opportunities of SpA in China; a discussion of the special needs in managing SpA in Ibero-America, and the SPARK Survey in Europe and North America.