ABSTRACT

In recent years, treatment options for both axial spondyloarthritis (axSpA) and peripheral spondyloarthritis (pSpA) have expanded significantly due to improvements in immunopathological information, thus allowing the use of targeted therapies. The development and validation of tumor necrosis factor inhibitor (TNFi) in spondyloarthritis (SpA) over the past two decades has revolutionized SpA management where previously effective treatment was inadequate. In recent years, TNFi biosimilars have been accepted for infliximab, adalimumab and etanercept, and have been shown to be effective and safe, and have begun to reduce costs for this class of drugs. Some new drugs for psoriatic arthritis (PsA) are being developed clinically. Anti-interleukin (IL)-17RA antibody brodalumab has phase 3 data, but the clinical program has been discontinued due to suicidal ideation in individuals. Studies on anti-IL17A/F antibody bimekizumab, antibodies against the subunit p19 of IL-23, guselkumab, tildrakizumab and risankizumab and several Janus Kinase (JAK) inhibitors are ongoing. Targeting IL-23 with anti-P40 or anti-P19 in axSpA did not show any significant improvement, and the development of these biological drugs was interrupted by this indication. Apremilast could not reach the primary end point in phase 3 study. Risankizumab did not show efficacy in ankylosing spondylitis (AS). Some other drugs, including Bimekizumab, are in the process of working in AS, and efficacy data are not currently available. A phase 3 study of tofacitinib in AS is ongoing (ClinicalTrials.gov NCT03502616). A phase 2 study of filgotinib, a highly selective JAK 1 inhibitor, has recently been reported to have reached the primary endpoint in patients with active AS. Upadacitinib, another selective JAK 1 inhibitor, has been shown to be effective in the study results in PsA and AS. The optimal dose and selectivity of JAK inhibition in SpA has not yet been established. Determining the important role of microbiome in AS is also an active area of research and treatments targeting the microbiome located in AS patients may be in the future. Studies are ongoing to develop small molecule inhibitors of the endoplasmic reticulum aminopeptidases to try in axSpA, with the strong genetic combination of Aminopeptidase genes ERAP1 and ERAP2 with AS. While effective biological therapies for non-radiographic axSpA (nr-axSpA) are limited to TNFi, secukinumab and ixekizumab were found to be effective and safe in nr-axSpA in phase 3 studies very recently. There are currently no registered JAK inhibitor studies for the treatment of nr-axSpA, but it is likely that there will be nr-axSpA trials if phase 3 studies in AS are successful. Finally, in parallel with the increase in pathophysiological information, future new treatment targets in SpA allow us to comment on targeting the intestinal-SpA interaction, including microbiota and integrins, on cellular actors such as innate lymphoid cells, mucosal associated invariant T cells, innate NK T cells. It is exciting for the doctor and patients to increase the treatment goals and thus expand the SpA treatment spectrum. At the same time, this diversity requires a more personalized treatment strategy with the differences to be considered in the choice of treatment.