Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment

Over the last decades biopharmaceuticals such as agents against tumor necrosis factor (TNF), are frequently prescribed to optimize rheumatoid arthritis treatment. Although TNF-inhibitors such as adalimumab, etanercept and infliximab, have improved the treatment of rheumatoid arthritis, a proportion of patients discontinue the treatment because of inefficacy or intolerance. Where TNF-inhibitor have failed, mainly two treatment approaches are available: switch to another TNF-inhibitor or to a biological with a different mode of action (notably rituximab, abatacept or tocilizumab) or to a target synthetic DMARDs. The EULAR recommendation for the management of rheumatoid arthritis advocate that any biologic agent including a subsequent TNF-inhibitor can be used with equal chance for effect in case of non-response to a previous TNF-inhibitor. Although it seems that indeed on a group level response to a non-TNF-inhibitor is comparable to a second TNF-inhibitor after the first TNF-inhibitor has failed, using therapeutic drug monitoring could identify subgroups of patient who would benefit more from either a non TNF-inhibitor or a TNF-inhibitor as next treatment. Here we explore the underlying pathophysiological mechanisms for this hypothesis.
Nonresponse on adalimumab in RA can have different causes. Firstly, the patient might not be sensitive to TNF blockade at all, or the patient develops this trait later on (primary nonresponse or secondary nonresponse). In these patients, switching to a non-TNF-inhibitor might conceptually be superior to starting a second TNF-inhibitor. However, in other patients nonresponse (either primary or secondary) might be caused by inefficient drug concentration because of development of antidrug antibodies against adalimumab. In these patients a TNF-inhibitor might be just as effective as a non-TNF-inhibitor, as these patients have drug- but not class failure. Thus, testing of adalimumab levels might be helpful in channelling patients to their most optimal treatment.However, a diagnostic study comparing a serum concentration guided versus usual care switching strategy has not yet been performed.

We hypothesis that a switching strategy based on adalimumab concentration is superior to usual care switching in rheumatoid arthritis patients failing adalimumab.

-2,4,12,24 weeks

Rheumatoid arthritis patients failing adalimumab treatment will be randomly assigned to switching strategy using drug concentration or usual care switching