A New Medical Therapy for Axial Spondyloarthritis / 대한내과학회지

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first choice of treatment for axial spondyloarthritis (axSpA); cyclooxygenase (COX)-2 inhibitors reduce both inflammation and bone formation. When NSAID treatment fails, tumor necrosis factor inhibitors (TNFis) can be used to treat active axSpA, but, presently, TNFis cannot completely prevent radiographic progression. Theoretically, as TNF is a strong pro-inflammatory cytokine triggering bone resorption, TNFis should stimulate bone formation. Recently, it was discovered that the IL-23/-17 axis is associated with enthesitis development and bone formation in a mouse model. The anti-IL-23 monoclonal antibody ustekinumab has been approved as treatment for moderate-to-severe plaque psoriasis and psoriatic arthritis. However, in axSpA patients, ustekinumab effectiveness was low and a phase 3 clinical trial was terminated. The anti-IL-17A monoclonal antibody secukinumab has been approved as treatment for moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In a 3-year extension of the MEASURE 1 observational study, the mean change in modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) from baseline to week 104 was 0.30 ± 2.53 among patients with evaluable X-rays originally randomized to secukinumab (n = 168). Such patients exhibited less radiographic progression compared to other TNFi studies. Several new drugs are in clinical trials exploring their effects on axSpA; these include ixekizumab (an anti-IL-17A monoclonal antibody), brodalumab (an anti-IL-17 receptor monoclonal antibody), and the Janus kinase (JAK) inhibitors tofacitinib and upadacitinib. The IL-23/-17 axis is important in terms of axSpA inflammation and bone formation. However, to date, no drug has completely prevented radiographic progression in axSpA patients.