Is the risk of infection higher during treatment with secukinumab than with TNF-inhibitors? : An observational study from the Nordic countries

Abstract

OBJECTIVES: The positioning of secukinumab in the treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) is debated, partly due to a limited understanding of the comparative safety of available treatments. We aimed to assess risk of the key safety outcome infections, during treatment with secukinumab and tumor necrosis factor inhibitors (TNFi). METHODS: Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IR) with 95% confidence intervals per 100 patient-years were calculated. Adjusted hazard ratios (HR) were estimated through Cox regression, with secukinumab as reference. Several sensitivity analyses were performed to investigate confounding by indication. RESULTS: Among 7708 patients with SpA and 5760 patients with PsA, we identified 16229 treatment courses of TNFi (53% bionaïve) and 1948 with secukinumab (11% bionaïve). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi in between. The adjusted HR for adalimumab, compared with secukinumab was 0.58 (0.39-0.85). In sensitivity analyses, the difference with secukinumab was somewhat attenuated and in some analyses no longer statistically significant. CONCLUSION: When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.