Bram Verstockt1,2, Gitte Moors1, Sumin Bian3, Thomas Van Stappen3, Gert Van Assche1,2, Séverine Vermeire1,2, Ann Gils3, Marc Ferrante1,2. 1. Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 2. Department of Clinical and Experimental medicine, Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. 3. Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven, Belgium.
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.
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 diseasepatients. METHODS: Serum samples from 116 biologically naive Crohn's diseasepatients 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.
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