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P505. ELISA vs. HMSA: a comparison between two different methods for the evaluation of adalimumab serum concentration and anti-adalimumab antibodies - Preliminary data

G. Bodini1, V. Savarino1,2, P. Dulbecco1,2, I. Baldissarro1,2, E. Savarino1,3,4, 1IRCCS San Martino Genova, Dipartimento di medicina interna, Genova, Italy, 2Università di Genova, Dipartimento di Medicina Interna, Genova, Italy, 3University of Padua, Department of Surgery, Oncology and Gastroenterology, padova, Italy, 4Department of Surgery, Oncology and Gastroenterology, University of Padua, gastroenteroly unit, padua, Italy

Background

Recent data showed that 20–30% of naïve patients with Crohn's disease (CD) are refractory to anti-TNFalfa drugs and up to 40% of patients in long-term therapy experience a loss of response. These phenomena are likely due to the reduction of drug serum levels and the development of anti-TNFalfa antibodies. Thus, there is increasing evidence regarding the need of dosing anti-TNFalfa concentrations and antibodies for their better management of them. However, to date, there are limited data on the diagnostic accuracy and utility of currently available kits for measuring anti-TNFalfa levels and antibodies on the market.

Methods

We compared serum Adalimumab (ADA) concentrations and anti-ADA antibodies (AAA) in consecutive CD patients during a 2-years follow-up period, analyzed by using a solid phase (double antigen) enzyme-linked immunoabsorbant assay (ELISA; Matriks Biotek) and an homogenous mobility shift assay (HMSA; Prometheus Lab).

In this prospective observational cohort study, performed at a single tertiary referral center, 22 [13M/9F; mean age 41 (range 20–66) infliximab-naïve patients with CD achieving disease remission and in maintenance treatment with ADA were included in a follow-up program. Blood samples were drawn at standardized time points (6, 12, 18, 24 months and in case of CD relapse) just before ADA injection. Trough serum concentration and antibodies against ADA were measured using the HMSA and ELISA methods. Disease activity was assessed at the same points by means of the Harvey–Bradshaw index (HBI, remission <5, mild disease 5–7, moderate disease 8–16, severe disease >16).

Results

For the preliminary analysis we have data from 129 blood samples. During the whole follow-up, ADA serum concentrations were significantly different between patients in remission (n = 8) and those who relapsed (n = 13), using HMSA (11.68 vs 6.12, p < 0.01) and ELISA (7.8 vs. 3.7, p < 0.01) methods, but the ELISA seemed to underestimate the levels of drugs in treated patients. Out of 13 patients with CD recurrence, 5 (65%) and 0 (0%) had detectable AAA based on HMSA and ELISA methods, respectively (p = 0.0391). Out of 5 patients who stopped anti-TNF-alfa therapy for CD recurrence, 5 (100%) and 0 (0%) had detectable AAA based on HMSA and ELISA methods, respectively (p = 0.0079). Among patients in remission, 3 and 1 had detectable AAA based on HMSA and ELISA methods, respectively (p = 1).

Conclusion

The use of ELISA method seems to underestimate the concentration of ADA levels in treated patients, although it was accurate enough to observe a significant difference between patients in remission and those who relapsed. On the other hand, HMSA was found to be superior than the ELISA method for AAA detection and this information was clinically significant.