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P385. Relationship between adalimumab concentration and efficacy for the induction of clinical remission in pediatric patients with moderate to severe Crohn's disease

R. Pradhan1, S. Sharma1, 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 of adalimumab concentration (conc) to remission or response following an induction dose in pediatric patients (pts) with moderate to severe Crohn's disease (CD).

Methods

Trough serum adalimumab conc and efficacy (response/remission) data were obtained at multiple time points from the 4-week (wk) open-label induction phase (160/80 mg or 80/40 mg at wk 0/2 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 (PCDAI reduction of ≥15 from baseline) and remission (PCDAI ≤10) at wk 4 in all patients. The trial's primary endpoint was PCDAI remission at Wk 26.

Results

At wk 4, the mean±SD (median) serum adalimumab conc (µg/mL) in remitters, 14.5±5.79 (15.2), was slightly higher (p = 0.280) than in non-remitters, 13.6±7.20 (13.1). Wk 4 response and remission rates were higher in pts with serum adalimumab conc above median (Figure 1). A clear exposure-response/remission relationship was evident.

Additional analyses were conducted to evaluate the effect of body weight on the exposure-remission relationship (Figure 2). A consistent exposure–remission relationship was observed in first and third weight tertiles.

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. Remission and response by adalimumab conc at Wk 4.

Figure 2. Remission by weight tertiles, adalimumab conc at Wk 4.

Conclusion

In general, increased exposure of adalimumab was associated with greater levels of efficacy in pediatric CD. Additional analyses are required to further quantify these relationships with respect to trough concentration cut-off values and efficacy outcomes.