Influence of early adalimumab serum levels on immunogenicity and long-term outcome of anti-TNF naive Crohn's disease patients: the usefulness of rapid testing

Abstract

Background: Proactive testing of adalimumab serum levels is debated.

Aim: To study the association between adalimumab serum levels at week 4 and the development of anti-adalimumab drug antibodies and long-term outcome in anti-TNF naive Crohn's disease patients.

Methods: Serum samples from 116 biologically naive Crohn's disease patients with active disease were prospectively collected at baseline, and weeks 4 and 12. Adalimumab serum levels were measured using the RIDA^® QUICK adalimumab lateral flow assay and anti-adalimumab drug antibodies were determined using a drug-resistant assay. Pharmacokinetic data were studied in relation to clinical outcome. Patients who stopped adalimumab by week 12 due to persisting symptoms were considered primary non-responders, whereas initial improvement with increasing symptoms after week 12 was considered loss of response. Adalimumab continuation until the end of follow-up was considered sustained clinical benefit.

Results: Patients with low serum levels at week 4 (<8.3 μg/mL) were at significantly higher risk of being anti-adalimumab positive by week 12 (46.7% vs 13.0%, P = 0.009). After a median follow-up of 89 weeks, dose-escalation and sustained clinical benefit were observed in 37.1% and 48.3% of patients. The 21.4% of patients who were anti-adalimumab drug antibody positive by week 12, had a significantly higher need of dose escalation (P < 0.001), and experienced sustained clinical benefit less frequently due to primary non-response or secondary loss of response (P = 0.02).

Conclusions: Our findings support early monitoring of adalimumab serum levels to guide dose optimisation, which may prevent immunogenicity and influence long-term outcome. We validated a novel lateral flow assay for quantitative determination of adalimumab levels, facilitating physicians to optimise therapy immediately at the outpatient clinic.