Promising Treatment Options for Axial Spondyloarthritis: An Overview of Experimental Pharmacological Agents

Abstract

Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that predominantly affects the axial skeleton. All patients receive conservative management measures which include physiotherapy, patient education and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Those with significant active disease will require escalation of their treatment with the use of biologics. Currently, there are five approved TNF inhibitors and two approved IL-17 inhibitors for use in axSpA. However, despite this up to 40% of patients do not respond or are intolerant to current available treatment. This leaves a significant number of patients with uncontrolled disease and unmet need for additional therapies. Though many drug classes have been trialed for axSpA they show poor efficacy; however, over the last few years there are three which demonstrate much greater promise as novel therapies for axSpA, these include dual neutralization of IL-17A and IL-17F, Janus kinase (JAK) inhibitors, and granulocytemacrophage colony-stimulating factor (GM-CSF) inhibitors. This article reviews the evidence for these novel emerging therapeutic options for axSpA.

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

“…starting in patients' mid-20s, 5 axSpA has a significant and lasting impact on patient lives [6][7][8] and a high disease burden. 3 Many patients with axSpA fail treatment, do not achieve treatment targets or experience residual symptoms, [9][10][11] demonstrating the need for more treatment options with novel modes of action. Interleukin (IL)-17A and IL-17F are key mediators of inflammation.…”

Therapeutic Targets for Ankylosing Spondylitis – Recent Insights and Future Prospects

“…Moreover, other evidences showed that overexpression of GM-CSF and its receptor have been found in the joints of axSpA patients where it could promote joint damage inducing the differentiation of granulocytes and macrophages into a more inflammatory phenotype. 15 , 54 , 55 Thus, inhibition of GM-CSF could be a promising future treatment for patients with axSpA.…”

“…Among the different drug classes, the anti-IL12/23 inhibitors ustekinumab and risankizumab, the T cell co-stimulation inhibitor abatacept, the IL-6 receptor inhibitors sarilumab and tocilizumab, the IL-1 receptor antagonist anakinra, the anti-CD20 antibody rituximab and the phosphodiesterase-4 inhibitor apremilast, were evaluated in clinical studies, but did not show sufficient efficacy in the treatment of axial disease. 15 To date, no data were published on the efficacy of IL-23 inhibitor guselkumab in patients with axSpA, although promising results coming from studies on psoriatic arthritis patients with axial involvement in which a significantly reduction in disease activity measure was found in respect to placebo group. 57 …”