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P524 Pharmacokinetics of adalimumab in paediatric subjects with moderate versus severe Crohn’s disease in Imagine-1

R. Singh*1, B. Kluender2, A. Robinson1, A. Lazar2, R. Thakkar1, N. Mostafa1

1AbbVie, North Chicago, United States, 2AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany

Background

Adalimumab has been shown to be effective and safe for induction and maintenance treatment of Crohn’s disease (CD) in paediatric subjects.1 A sub-group analysis found meaningful efficacy in patients with both moderate and severe disease, as defined by PCDAI, at baseline (BL).2 The purpose of the current work was to assess the pharmacokinetics (PK) of adalimumab in paediatric subjects with CD by disease severity category at BL.

Methods

Serum adalimumab trough concentrations (Ctrough) in paediatric subjects with CD who participated in the IMAgINE-1 study were analysed to assess potential differences in adalimumab PK in moderate [PCDAI<40] versus (vs) severe [PCDAI≥40] disease sub-groups at BL. Subjects (n = 188) were categorised in 4 treatment groups: (1) Induction dose (IndD) of 160/80 mg on week 0/2 (160/80 mg) followed by 40 mg eowk maintenance dose (MD) from week 4 to week 52; (2) IndD of 160/80 mg followed by 20 mg eowk MD; (3) IndD of 80/40 mg on week 0/2 (80/40 mg) followed by 20 mg eowk MD; and (4) IndD of 80/40 mg followed by 10 mg eowk MD. Within each treatment group, Ctrough values were compared between paediatric subjects with moderate vs severe CD at BL. The clearance (CL) and volume of distribution (Vd) estimates in individual subjects from the population PK (PopPK) model3 were also compared for subjects with moderate vs severe CD. Disease severity at BL was also tested as a categorical covariate for both CL and Vd, separately.

Results

Comparison of Ctrough values within each treatment group revealed no apparent differences between paediatric subjects with moderate vs severe CD (Figure 1).

Figure 1. Adalimumab C trough by time interval in paediatric subjects with CD by disease severity at BL in each treatment group of IMAgINE-1.

The medians and ranges of CL and Vd in subjects with moderate CD were comparable with their corresponding values in paediatric subjects with severe CD. The ranges of CL in subjects with moderate and severe CD were 0.090–0.795 and 0.091–0.864 L/day, respectively. Similarly, the ranges of Vd in subjects with moderate and severe CD were 2.38–8.42 and 2.27–12 L, respectively. Disease severity category was not a significant (p > 0.05) covariate on CL and Vd.

Conclusion

PK of adalimumab in paediatric subjects with moderate and severe CD at BL was similar in the IMAgINE-1 study.

References:

[1] Hyams JS, Griffiths A, Markowitz J, et al. Safety and efficacy of adalimumab for moderate to severe Crohn’s disease in children. Gastroenterol 2012;143(2):365–74.

[2] Rummel F, Crandall W, Rosh J, et al. Efficacy and safety of standard vs low dose adalimumab maintenance therapy as a function of disease severity in paediatric patients with Crohn’s disease: Subanalysis of IMAgINE 1, ESPGHAN 2013.

[3] Sharma S, Eckert D, Hyams JS, et al. Pharmacokinetics and exposure-efficacy relationship of adalimumab in paediatric patients with moderate to severe Crohn’s disease: results from a randomised, multiCentre, phase-3 study. Inflamm Bowel Dis 2015;22(4): 783–92.