Several factors can predispose to primary and secondary treatment failure. In patients with primary treatment failure, subtherapeutic levels may indicate poor adherence or increased drug clearance, or other pharmacokinetic issues.
In patients with secondary failure, subtherapeutic drug levels may also be caused by the development of anti-drug antibodies; that is, antibodies that target and lower the bioavailability of TNF-alpha inhibitors. The immunogenicity of TNF-alpha inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) was investigated in a meta-analysis of 68 studies (14,651 patients) performed from 1966 to 2013. In that study, anti-drug antibodies were detected more often in patients treated with infliximab (25%) than in those treated adalimumab (14%), certolizumab (6.9%), golimumab (3.8%), or etanercept (1.2%).9 Development of anti-drug antibodies reduced the odds of clinical response by 67% overall, although nearly half of the data were derived from articles involving infliximab or adalimumab.