TY - JOUR
T1 - Post-Induction High Adalimumab Drug Levels Predict Biological Remission at Week 24 in Patients With Crohn's Disease
AU - Zittan, Eran
AU - Steinhart, A. Hillary
AU - Goldstein, Pavel
AU - Milgrom, Raquel
AU - Gralnek, Ian M.
AU - Silverberg, Mark S.
N1 - Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
PY - 2021/10/6
Y1 - 2021/10/6
N2 - INTRODUCTION: We investigated whether early adalimumab drug levels (ADL) at week 4 predicted biological remission at week 24. METHODS: In a prospective study, we assessed clinical and biological remission at weeks 0, 4, 12, and 24 after induction of adalimumab in 33 patients with Crohn's disease. Disease activity was determined by the Harvey-Bradshaw Index, ileocolonoscopy reports, cross-sectional imaging, C-reactive protein (CRP), and fecal calprotectin (FC) levels. Clinical remission was defined as Harvey-Bradshaw Index <5. Biological remission was defined as a combination of FC < 200 μg/g and CRP <5 μg/mL. ADL trough levels were tested using a liquid phase, mobility shift assay. RESULTS: At 24 weeks, 18/33 (55%) of the patients were with biological remission. Ten (30%) patients required dose escalation or withdrawal from adalimumab by week 24 because of lack of response and exhibited significantly higher FC (P = 0.003) and CRP (P = 0.002). ADL levels at week 4 (19.8 μg/mL vs 10.2 μg/mL, P = 0.001) were significantly higher in patients with biological remission vs nonresponders at week 24. ADL levels at week 4 were a good predictor of biological remission at week 24, with area under the curve 0.86, 95% confidence interval (1.1; 1.67) and for combined biological and clinical remission, with area under the curve 0.8. The best ADL cutoff at week 4 that predicted biological remission at week 24 was 13.9 μg/mL (sensitivity 94.4% and specificity 73.3%). DISCUSSION: In individuals with Crohn's disease, higher adalimumab drug levels at week 4 (>13.9 μg/mL) were significantly associated with biological remission at week 24.
AB - INTRODUCTION: We investigated whether early adalimumab drug levels (ADL) at week 4 predicted biological remission at week 24. METHODS: In a prospective study, we assessed clinical and biological remission at weeks 0, 4, 12, and 24 after induction of adalimumab in 33 patients with Crohn's disease. Disease activity was determined by the Harvey-Bradshaw Index, ileocolonoscopy reports, cross-sectional imaging, C-reactive protein (CRP), and fecal calprotectin (FC) levels. Clinical remission was defined as Harvey-Bradshaw Index <5. Biological remission was defined as a combination of FC < 200 μg/g and CRP <5 μg/mL. ADL trough levels were tested using a liquid phase, mobility shift assay. RESULTS: At 24 weeks, 18/33 (55%) of the patients were with biological remission. Ten (30%) patients required dose escalation or withdrawal from adalimumab by week 24 because of lack of response and exhibited significantly higher FC (P = 0.003) and CRP (P = 0.002). ADL levels at week 4 (19.8 μg/mL vs 10.2 μg/mL, P = 0.001) were significantly higher in patients with biological remission vs nonresponders at week 24. ADL levels at week 4 were a good predictor of biological remission at week 24, with area under the curve 0.86, 95% confidence interval (1.1; 1.67) and for combined biological and clinical remission, with area under the curve 0.8. The best ADL cutoff at week 4 that predicted biological remission at week 24 was 13.9 μg/mL (sensitivity 94.4% and specificity 73.3%). DISCUSSION: In individuals with Crohn's disease, higher adalimumab drug levels at week 4 (>13.9 μg/mL) were significantly associated with biological remission at week 24.
UR - http://www.scopus.com/inward/record.url?scp=85118067312&partnerID=8YFLogxK
U2 - 10.14309/ctg.0000000000000401
DO - 10.14309/ctg.0000000000000401
M3 - Article
C2 - 34613952
AN - SCOPUS:85118067312
VL - 12
SP - e00401
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
SN - 2155-384X
IS - 10
ER -