Drug immunogenicity in patients with inflammatory arthritis and secondary failure to tumour necrosis factor inhibitor therapies: the REASON study.

Objectives: The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response.

Methods: This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA.

Results: Among 570 evaluable patients, those with RA (n = 276) were mostly female (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and had maintained good clinical disease control for longer (202 vs 170 weeks) compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%) patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations. Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those with RA (21.1%; P = 0.014). A significantly lower proportion of patients receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy (26.4%; P < 0.05).

Conclusion: In patients with RA or SpA and secondary failure, the development of ADA against ADL or INF, but not ETN, appears to be one of the main reasons for secondary treatment failure, but not the only one. Further investigations are needed to determine other causes of anti-TNF failure.