Make sense who may. I switch off. Samuel Beckett (1984)

The registration, almost simultaneously, of etanercept and infliximab, followed some years later by that of adalimumab, presented rheumatologists with outstanding therapeutic options to the benefit of many patients. Nevertheless, it also became clear that none of these drugs are effective in all cases, and the question about switching from one anti-tumour necrosis factor (TNF) to another became an important clinical issue. As we wrote 4 years ago in the Annals of the Rheumatic Diseases: “in these situations, [is] there a rationale for prescribing the other TNFα blocker, or [is this] simply a waste of time and money?”.¹ Since that publication, a sizeable number of research articles have investigated this question, and the answers have generally been in the affirmative, implying that, yes, a switch of this type can benefit some patients.^{2,3,4,5,6,7,8,9,10,11,12,13,14,15,16} However, some reports reached less favourable conclusions,^17,18 and it can rightfully be asserted that none of those published studies, nor any of the many abstracts presented at international meetings on the topic, were controlled, prospective, randomised or blinded.

Perhaps the importance and depth of the issue of switching between anti-TNFs has not been sufficiently appreciated. For one thing, the question of switching is not only a question of clinical practice, but has an important scientific dimension as well: a true demonstration that one anti-TNF agent has efficacy in the same patient who failed to respond to another suggests something potentially important about the pathophysiological process in that individual, leading to interesting possibilities for “bedside-to-bench” research. A …