Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn’s Disease: A Retrospective, International Multicenter Study

• Published in: Inflammatory bowel diseases 2024-10, Vol.30 (10), p.1714-1723
• Main Authors: Little, Robert D, Swaine, Adrian, Reynolds, Rebecca, Gibson, David J, Barrau, Mathilde, D’Errico, Francesca, Hampal, Rumneek, Sparrow, Miles P, Roblin, Xavier, Irving, Peter M, Ward, Mark G
• Format: Article
• Language: English
• Subjects: Adalimumab - administration & dosage; Adalimumab - therapeutic use; Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; Crohn Disease - drug therapy; Dose-Response Relationship, Drug; Drug Monitoring - methods; Female; Humans; Male; Middle Aged; Remission Induction; Retrospective Studies; Treatment Outcome; Young Adult
• ISSN: 1078-0998; 1536-4844; 1536-4844
• DOI: 10.1093/ibd/izad248

Abstract Background The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn’s disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. Methods We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein 10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. Conclusions Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission. Lay Summary Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn’s disease remission.