The impact of the interleukin 12/23 inhibitor ustekinumab on the risk of infections in patients with psoriatic arthritis

Introduction: Psoriatic arthritis (PsA) is characterized by chronic inflammation mediated by pro-inflammatory cytokines, with clinical features resulting from dysfunctional integrated signaling pathways affecting different constituents of the immune system. Increased understanding of the processes responsible for enthesitis, synovial inflammation, joint erosion, and new bone formation during PsA has led to development of biologic therapies targeting these cytokines. There is an increased risk of opportunistic infections in patients with PsA, and this risk is increased further with targeted biologic therapy. Areas covered: This paper reviews the role of the interleukin (IL)-12, IL-23 and IL-17 axis in the pathogenesis of PsA. The data suggest that ustekinumab is associated with a low risk of infections in patients with PsA, including tuberculosis or hepatitis reactivation. No live vaccines can be safely administered; ustekinumab is contraindicated/cannot be given with live vaccines. However, long-term treatment with ustekinumab does not impair the immune response to these vaccines when administered after an appropriate interval. Expert opinion: Ustekinumab is associated with a low risk of serious and opportunistic infections. More research is needed to confirm these findings specifically in patients with PsA, and comparative studies are needed to investigate the relative risk of infection with different biologics.