Background: Drug concentration monitoring may be useful to guide therapeutic adjustments for anti–tumor necrosis factor agents in Crohn's disease. The relationship between serum adalimumab concentrations and clinical outcomes was assessed using data from CLinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease (CLASSIC) I/II.
Methods: Serum adalimumab concentrations at week 4 of CLASSIC I and weeks 4, 24, and 56 of CLASSIC II were compared by clinical remission status (yes/no). Logistic regression and Classification and Regression Tree analyses explored factors associated with remission at weeks 4, 24, and 56. Threshold analyses and receiver operating characteristic curves evaluated the relationship between serum concentrations and clinical remission/response.
Results: Serum adalimumab concentrations for 275 patients were available. Median adalimumab concentrations were significantly higher in patients who achieved clinical remission than those who did not at week 4 of CLASSIC I (8.10 versus 5.05 µg/mL, P < 0.05). At all time points, adalimumab concentrations demonstrated considerable variability and overlap between patients with and without remission. With Classification and Regression Tree analyses, baseline Crohn's Disease Activity Index, baseline C-reactive protein, and adalimumab concentrations were associated with early remission at week 4 of CLASSIC I and week 4 of CLASSIC II, but not at weeks 24 and 56. Receiver operating characteristic curves demonstrated low utility of cutoff thresholds to discriminate by clinical response/remission status.
Conclusions: A positive association between serum adalimumab concentration and remission was identified at several time points. A threshold concentration reliably associated with remission was not identified. Further prospective evaluations are needed before recommendations for adalimumab concentration monitoring can be made.
Article first published online 11 April 2013
*AbbVie Inc., North Chicago, Illinois;
†Department of Medicine, Gastroenterology and Nutrition, University of Chicago Medical Center, Chicago, Illinois;
‡Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium; and
§Unit of Hepatology and Gastroenterology, Department of Clinical Sciences, Centre Hospitalier Universitaire de Liège and GIGA-Research Université de Liège, Liege, Belgium.
Reprints: Yi-Lin Chiu, Biometrics Clinical Pharmacology and Pharmacometrics, AbbVie, AP9A-1, 1 North Waukegan Road, North Chicago, IL 60064 (e-mail: email@example.com).
Supported by AbbVie Inc.
Dr. D. T. Rubin reports having been a consultant, served on an advisory board, and received grant/research support from AbbVie Inc. and UCB; and has also been a consultant and served on an advisory board for Centocor (now Janssen). Dr. S. Vermeire reports having been a speaker and received consulting fees from Ferring, Novartis and Shire and has received consulting fees, been a speaker, and received grant/research support from AbbVie Inc., Centocor, MSD and UCB. Dr. E. Louis reports having received speaker and consultancy fees, and research for educational grants from AbbVie Inc., MSD, and Schering Plow. Drs. Y.-L. Chiu and A. M. Robinson are employees of and shareholders in AbbVie Inc. Drs. S. K. Paulson, K. G. Lomax, and P. F. Pollack are former employees of AbbVie Inc.
The authors have no other conflicts of interest to disclose.
Received August 29, 2012
Accepted September 19, 2012