Lack of efficacy of a third tumour necrosis factor α antagonist after failure of a soluble receptor and a monoclonal antibody

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Abstract
Objective. Some studies have highlighted the potential benefits of switching from infliximab to etanercept, or after failure of one or the other treatment. To our knowledge, no study has assessed the potential benefits of using the three anti-TNF-α agents that are currently available. The objective of this retrospective study was to assess the response to treatment in RA patients who had received the three anti-TNF-α agents, namely infliximab, etanercept and adalimumab. Methods. Among a cohort of 364 patients undergoing biological treatments since the year 2000, 284 had been treated with only one anti-TNF-α agent. Our assessment focused on the records of 70 patients who had received at least two anti-TNF-α agents. Twenty of the 70 patients had received all three anti-TNF-α agents (infliximab, etanercept and adalimumab). Effectiveness was assessed using the 28-joint Disease Activity Score (DAS28), and adverse events were reported for each anti-TNF-α treatment. Results. Of the 70 patients who had received two anti-TNF-α agents, 32 had switched from an antibody to a soluble receptor; 45% of them had a good clinical response to the soluble receptor. Thirty patients had switched from a soluble receptor to an antibody; 45% of them had a good clinical response to the antibody. Only eight patients had switched from an antibody to another antibody with an efficiency score of 33%. Of the 20 patients who had received three anti-TNF-α agents, seven had stopped receiving the third anti-TNF-α agent due to lack of effectiveness. In this group of non-responders to the third anti-TNF-α treatment, all patients except one had stopped receiving the two previous anti-TNF-α agents, without adverse events, for lack of effectiveness. These patients were deemed resistant to anti-TNF-α therapy. Conclusions. Resistance to anti-TNF-α agents is rare. The lack of effectiveness of a soluble receptor and of one of the anti-TNF-α antibodies predicts the lack of effectiveness of the third anti-TNF-α treatment.

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