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.

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, week 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 nonresponders, whereas initial improvement with increasing symptoms after week 12 was considered loss of response. Adalimumab continuation till 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 to be 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 significant higher needs for dose escalation (P < 0.001), and experienced sustained clinical benefit less frequently due to primary nonresponse 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, facilitating physicians to optimise therapy immediately at the outpatient clinic.