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P536. Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn's disease

C. Steenholdt1, K. Bendtzen2, J. Brynskov1, O.Ø. Thomsen1, M.A. Ainsworth1, 1Herlev University Hospital, Department of Gastroenterology, Herlev, Denmark, 2Rigshospitalet, University Hospital of Copenhagen, Institute for Inflammation Research, Copenhagen, Denmark

Background

Cost-effective guidance of therapeutic strategy in Crohn's disease patients with treatment failure during infliximab (IFX) maintenance therapy can be achieved by IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA) to identify underlying mechanisms for failure and corresponding interventions [1]. This study investigated implications of using different analytical techniques for this purpose.

Methods

Post-hoc analysis of randomized clinical trial including 66 patients with secondary IFX failure in whom IFX and anti-IFX Ab measurements by RIA had been used for therapeutic guidance (Biomonitor A/S, DK) [1] Samples were additionally assessed by enzyme-linked immunosorbent assay (ELISA) [2] and homogeneous mobility shift assay (HMSA) [3] (both Prometheus Laboratories Inc., USA); and a functional reporter gene assay (RGA) (Biomonitor A/S) [4].

Results

IFX detection was comparable between assays (82% of patients in RIA, 76% ELISA, 88% HMSA, 74% RGA), and correlated significantly (Pearson r 0.91–0.97, p < 0.0001). However, IFX concentrations varied systematically between all pair of assays except RIA-RGA, and could not be compared directly. Anti-IFX Ab detection was variable (27% of patients in RIA, 9% ELISA, 33% HMSA, 11% RGA), but correlated significantly (0.77–0.96; p < 0.0001). Abs detected by RIA and HMSA were often from sera without drug-neutralizing activity (RGA). Assays agreed on classification of underlying mechanism for treatment failure in 79–94% of cases. The majority (74–88%) failed IFX due to pharmacodynamic problems or had non-inflammatory causes for symptoms resembling relapse. Applied threshold for therapeutic vs. sub-therapeutic IFX level strongly influenced classifications. The assays did not differ in terms of ability to predict response to interventions defined by the algorithm.

Conclusion

Despite differences in analytical properties, common assays result in similar classifications and interventions in patients with IFX treatment failure, and with comparable clinical outcomes. Implications are, however, profound for the minority classified differently.

1. Steenholdt C et al. Gut 2013 Jul 22 [Epub ahead of print].

2. Afif W et al. Am J Gastroenterol 2010: 1133–9.

3. Wang SL et al. J Immunol Methods 2012: 177–88.

4. Lallemand C et al. J Immunol Methods 2011: 229–39.