[Switching within the active ingredient group or changing the mechanism of action. Data situation by failure of the...

Despite the use of biologics many patients do not achieve remission or reduced disease activity, which raises the question of the optimal therapy when these therapy targets are not achieved. Most data from clinical studies and registry data refer to the approach following the unsuccessful use of one or more tumor necrosis factor (TNF) inhibitors. Randomized controlled studies investigating the effectiveness of a further biologic or TNF inhibitor in patients who received abatacept, tocilizumab or rituximab in the first line therapy are currently lacking, with the exception of the German MIRAI study. The majority of registry data and observational studies suggest that when the use of a TNF inhibitor is unsuccessful it is advantageous to change to a non-TNF biologic. This does not exclude that a change within the group of TNF inhibitors can represent an appropriate option, e.g. by injection or infusion reactions or secondary therapy failure. Whether determination of serum levels and neutralizing antibodies aids decision-making for individual patients, must currently remain open. The option to change within an active ingredient group of biologics only currently applies to the group of TNF inhibitors; however, with the development of further antibodies inhibiting interleukin 6, this question will also apply to this group of substances. The question of the optimal strategy after failure of the first and second line biologics will be asked more frequently when the therapy targets of remission and low disease activity are more stringently strived for. Predictive markers for an optimal approach to the sequential administration of biologics are lacking. In order to answer this question clinical studies which investigate the therapeutic approach in a randomized and controlled manner will be necessary in the future.