The pharmacological and clinical aspects behind dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs): rationale and systematic narrative review of clinical evidence

Abstract

Abstract Background Dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs) is performed to achieve steady state drug concentrations earlier after treatment start compared to dosing regimens without loading. Although loading inherently results in increased costs, treatment targets in terms of reduced disease activity may be achieved at an earlier state. It is an interesting topic that, surprisingly, has not received much attention in literature. Methods In this review, we aimed at providing a theoretical description of the pharmacodynamic / -kinetic rationale for dose loading of bDMARDs in AIRDs and to systematically review the clinical evidence on the effectiveness of dose loading on disease activity in AIRDs. Results Only a small number of studies (n = 5) has been published comparing the effectiveness of dose loading versus a regimen without dose loading of bDMARDs in AIRDs, addressing abatacept (n = 2), certolizumab pegol (n = 1), and secukinumab (n = 2). These studies provide insufficient evidence on superiority of dose loading in terms of disease activity compared to a dosing regimen without loading, while safety issues might be comparable. Conclusions Although dose loading is commonly adopted for several bDMARDs in AIRDs, scientific evidence on its effectiveness and safety is surprisingly scarce and does not suggest superiority compared to a regimen without dose loading. More research in this field, also with regard to the pharmaco-economic consequences of dose loading, is urgently needed.