Emerging Immunomodulatory Therapies and New Treatment Paradigms for Axial Spondyloarthritis Abstract Purpose of Review The purpose of this review is to educate the reader about the evolving classification of axial spondyloarthritis (AxSpA) and describe recent treatment data from clinical trials of medications with mechanisms of action other than TNF inhibition. The review will also address emerging treatment strategies for AxSpA. Recent Findings New and more sensitive classification schema for AxSpA find that the prevalence of the disease is more than twice that of the historic definition of ankylosing spondylitis (AS), when patients without radiographically observable damage to the sacroiliac joints are included. TNF inhibitors have shown efficacy in the full spectrum of disease. IL-17 inhibitors, e.g., secukinumab and ixekizumab and janus kinase (JAK) inhibitors, have shown good efficacy and relatively good safety in radiographically defined AxSpA and are being tested in non-radiographic (nr) AxSpA. Several immunomodulatory medicines approved for psoriasis, psoriatic arthritis, and rheumatoid arthritis have not shown efficacy in AxSpA, highlighting the importance of conducting good-quality, placebo-controlled trials in this condition. Treatment strategies such as “treat to target” and tapering therapy are being studied. Summary There remains a large unmet need to identify and adequately treat the full spectrum of AxSpA. The use of TNF inhibitors has improved our ability to achieve remission or low disease activity in AxSpA. Newer medicines with different mechanisms of action, e.g., IL-17 or JAK inhibition, are also showing similar ability. Continued research, including identification of new targets of treatment, is critical.