Spatial functional principal component analysis and its application in diagnostics

In this thesis the nonparametric functional principal component analysis is extended to spatial data. The estimation is implemented in an R package and the implementation is evaluated comparing estimated eigenfunctions of realizations of a Wiener process to the theoretic ones. Furthermore, consistency results for the estimators are derived theoretically. Both, the one- and the two-dimensional method are used to evaluate several real data examples from the medical field, especially diagnostics

Risankizumab: Mechanism of action, clinical and translational science

Abstract Risankizumab is a high‐affinity neutralizing anti‐interleukin (IL)‐23 monoclonal antibody marketed in over 40 countries across the globe to treat several inflammatory diseases, such as plaque psoriasis (PsO), psoriatic arthritis (PsA), and Crohn's disease (CD). This paper reviews the regulatory approval, mechanism of action, pharmacokinetics (PKs)/pharmacodynamics, immunogenicity, and clinical efficacy and safety data for risankizumab, focusing on the three main approved indications. Risankizumab binds to the p19 subunit of IL‐23 and inhibits IL‐23 from interacting with the IL‐23 receptor and subsequent signaling. Biomarker data obtained following treatment with risankizumab in multiple indications provided supportive evidence for downstream blockade of IL‐23 signaling associated with disease pathology. The PKs of risankizumab is linear and time‐independent, consistent with typical IgG1 monoclonal antibodies, across all evaluated indications. Risankizumab exhibited positive exposure‐response relationships for efficacy with no apparent exposure‐dependent worsening in safety. Immunogenicity to risankizumab had no major clinical consequences for either efficacy or safety. Efficacy and safety of risankizumab have been established in PsO, PsA, and CD in the pivotal clinical trials where superior benefit/risk profiles were demonstrated compared to placebo and/or active comparators. Moreover, safety evaluations in open‐label extension studies following long‐term treatment with risankizumab showed stable and favorable safety profiles consistent with shorter‐term studies. These data formed the foundation for risankizumab's marketing approvals to treat multiple inflammatory diseases across the globe