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P384. Relationship between adalimumab concentration and efficacy for the maintenance of clinical remission in pediatric patients with moderate to severe Crohn's disease

S. Sharma1, R. Pradhan1, R. Thakkar1, A. Robinson1, J. Hyams2, J. Rosh3, F.M. Ruemmele4, W. Awni1, 1Abbott Laboratories, United States, 2Connecticut Children's Med Ctr, United States, 3NJ Medical School, United States, 4Hôpital Necker-Enfants Malades, France

Background

The purpose of this analysis was to characterize the relationship between adalimumab concentration (conc) and remission or response following maintenance dosing in pediatric patients (pts) with moderate to severe Crohn's disease (CD).

Methods

Serum trough adalimumab conc and efficacy (response/remission) data were obtained at multiple time-points from the 48-week (wk) double-blind maintenance phase (High-Dose of 40 mg or 20 mg or Low-Dose of 20 mg or 10 mg every other week (eow) based on body weight cut-off of 40 kg) of a 52-wk study. Pediatric Crohn's Disease Activity Index (PCDAI) was used to quantify clinical response (defined as a reduction of PCDAI of ≥15 from baseline) and remission (defined as a PCDAI of ≤10). The trial's primary endpoint was PCDAI remission at wk 26.

Results

Adalimumab trough conc (Mean±SD; µg/mL) following the High-Dose and Low-Dose regimens in subjects achieving remission (remitters) and non-remitters are shown in the table.

The rate of response and remission at wk 26 and 52 increased with adalimumab trough conc (exposure) above the median conc (Figure 1) indicating an exposure-response/remission relationship.

Sex, Baseline PCDAI, plasma CRP levels and prior anti-TNF treatment did not have a statistically significant effect on the exposure-response/remission relationship.

Figure 1. Percent remission and response by adalimumab conc at Wk 26 and Wk 52.

RegimenWeekRemittersNon-Remittersp-value*
Low-dose264.52±3.214.73±4.610.616
 525.60±3.805.36±4.130.561
High-dose2611.3±4.8510.5±10.40.028
 5213.3±8.449.85±8.510.112
*Statistical comparison of adalimumab trough conc in remitters versus non-remitters.

Conclusion

Adalimumab trough conc were higher in remitters than non-remitters in both dosing groups. Higher conc of adalimumab were associated with greater levels of efficacy in pediatric CD. Additional analyses are required to further quantify these relationships with respect to specific trough concentration cut-off values and efficacy outcomes.