Adalimumab Clearance, rather than Trough Level, May Have Greatest Relevance to Crohn's Disease Therapeutic Outcomes Assessed Clinically and Endoscopically.

2023-08-18

Wright, Emily K

Chaparro, Maria

Gionchetti, Paolo

Hamilton, Amy L

Schulberg, Julien

Gisbert, Javier P

Valerii, Maria Chiara

Rizzello, Fernando

De Cruz, Peter P

Panetta, John C

Everts-van der Wind, Annelie

Kamm, Michael A

Dervieux, Thierry

Adalimumab

Clearance

Crohn’s disease

pharmacokinetics

Journal Article

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0000-0002-9275-4242

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0000-0002-1627-2057

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0000-0003-2090-3445

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#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

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10.1093/ecco-jcc/jjad140

We postulated that adalimumab (ADA) drug clearance (CL) may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease (CD) patients undergoing ADA maintenance treatment. CD patients from 4 cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission (ER), sustained -reactive protein (CRP) based clinical remission (defined as CRP levels below 3 mg/L in the absence of symptoms) and fecal calprotectin (FC) level below 100µg/g. Serum albumin, ADA concentration and anti-drug antibody status were determined using immunochemistry and homogenous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann-Whitney test, and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. In 237 enrolled patients (median age 40 years, 45% females), median CL was lower in patients achieving ER as compared to those with persistent active endoscopic disease (median 0.247 L/day vs 0.326 L/day, respectively) (p<0.01). There was no significant difference in ADA concentration between patients in endoscopic remission compared to those with recurrence (median 9.3 µg/mL vs 11.7 µg/mL, respectively). Sustained CRP-based clinical remission and FC levels below 100µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. Lower ADA Clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration.

link

Journal of Crohn's & Colitis 2023-08-18

Journal of Crohn's & Colitis

1876-4479