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 granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibitors. This article reviews the evidence for these novel emerging therapeutic options for axSpA.

Keywords: Axial spondyloarthritis; GM-CSF inhibitors; IL-17 inhibitors; JAK inhibitors; novel therapies.

Figure 1

(A) The JAK-Stat signalling pathway. (B) Cytokine signally through JAK/STAT combination. Adapted from Bechman K, Yates M, Golloway J. The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors. Pharmacol Res. 2020; 153: 104634. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Adapted from Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002;285 (1–2):1–24. Feb 20. Copyright 2002, with permission from Elsevier. Adapted from Hodge AJ, Kawabata TT, Krishnaswami S, et al. The mechanism of action of tofacitinib – an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016; 34 (2):318-328.