Sequential use of biologic therapy in rheumatoid arthritis

With an increasing range of biological therapies available in the management of rheumatoid arthritis, sequencing of such therapies is becoming more frequent, particularly with more ambitious treatment aims. This review will address the evidence to date on use of successive targeted agents.

Double-blind, randomized controlled trials have confirmed the role of alternative tumour necrosis factor (TNF) inhibitors (TNFi), rituximab, abatacept and tocilizumab, following TNFi failure with no comparative studies to date. Registry data have demonstrated efficacy of switching from a first to a second TNFi. Observational experience has confirmed benefits of switching from TNFi to TNFi and TNFi to rituximab. Within available randomized controlled trial data, tocilizumab appears effective in TNFi failure group, irrespective of number of TNFi previously failed. Such data are not available for the other agents. No safety signals have been identified thus far with biologic sequencing. Although formal comparative, controlled studies do not exist, type of previous failure to TNFi and disease characteristics (serology, comorbidity, concomitant therapy) can provide a good platform for choosing the next biologic treatment.

Although biological sequencing is well established, optimal approach represents a significant knowledge gap; well designed clinical studies with associated mechanistic investigation are necessary to identify disease subgroups that would benefit from one sequence over another.