S1290 Efficacy, Safety, and Pharmacokinetics of Infliximab Dose Escalation in Pediatric Patients With Crohn’s Disease or Ulcerative Colitis: An Analysis of the DEVELOP Registry

Introduction: Pediatric patients (pts) with inflammatory bowel disease (IBD) being treated with infliximab (IFX) may undergo dose escalation. DEVELOP is a multicenter, global, prospective, observational registry of long-term safety and clinical status of 6069 pts with IBD. We evaluated the efficacy, safety, pharmacokinetics (PK), and immunogenicity of IFX among pts with Crohn’s disease (CD) or ulcerative colitis (UC) who had dose escalation from 5 to 10 mg/kg q8w. Methods: In DEVELOP, data are collected every 6 months (mos). This analysis included pts (≤ 18 years) who received ≥ 1 escalated IFX dose of 10 mg/kg after ≥ 2 doses of 5 mg/kg. Data were collected within 12 mos before escalation and after escalation in the first 3 mos and at 12 (± 3) mos. Efficacy was assessed by the proportions of pts in response or remission using the Pediatric Crohn’s Disease Activity Index (PCDAI) criteria for CD and partial Mayo for UC (Table 1). Safety was assessed by adverse events (AEs). Results: Of the 262 dose-escalated pts (221 CD, 41 UC; 44% female; 83% white; median age 15 years), the majority (62% CD; 77% UC) were in remission at the time of dose escalation, with small changes in remission noted at 3 mos and 12 mos after escalation (Table 1). In a subgroup of 71 CD pts with active disease (PCDAI ≥ 10) within 60 days before escalation and ≥ 1 post dose escalation PCDAI measurement, approximately 34% had clinically meaningful improvement (PCDAI improvement ≥ 10 points) after escalation (Figure 1), with 37% in remission at 12 mos after escalation. The numbers of pts/100 pt-years experiencing AEs, infections, and serious AEs were generally similar before/after escalation. Infusion reactions increased from 0.34% (1/294) of infusions within 3 mos before to 2.33% (13/558) within 3 mos after escalation. For 39 dose escalated pts in a PK/immunogenicity substudy, median trough IFX levels increased slightly from 1.18 μg/mL before to 3.21 μg/mL after escalation; 74% of pts with samples had antibodies to IFX (ATI) before (n=23, ≤ 1:3200; n=3, > 1:3200) and 76% after (n=20, ≤ 1:3200; n=2, > 1:3200) escalation. Conclusion: These real-world data reveal that many pts treated with IFX were positive for ATI before dose escalation and were dose escalated while in clinical remission. There appears to be some clinical benefit of IFX dose escalation in pediatric pts with CD that is evident 12 mos later, although of modest magnitude, with a slight increase in infusion reactions and little change in immunogenicity.Figure 1.: Distribution of Change in Pediatric Crohn’s Disease Activity Index (PCDAI) Scores for Crohn’s Disease Patients With Active Disease at Infliximab (IFX) Dose Escalation (N = 71). Change measured from last visit before escalation to first visit after escalation. Includes pts who received ≥ 1 escalated IFX dose of 10 mg/kg after ≥ 2 maintenance IFX doses of 5 mg/kg plus PCDAI score ≥ 10 within 60 days before escalation and ≥ 1 post dose escalation PCDAI measurement. Note: a decrease in PCDAI score represents an improvement of disease activity, whereas an increase in PCDAI score represents a worsening of disease activity.Table 1.: Proportions of Pediatric Patients in Clinical Response or Clinical Remission At and After Infliximab (IFX) Dose Escalation From 5 mg/kg to 10 mg/kg.

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