Natalizumab Therapy for Moderate to Severe Crohn Disease in Adolescents

ABSTRACT Objectives: This study evaluated the safety, tolerability, and efficacy of natalizumab, a humanized monoclonal immunoglobulin‐G4 antibody to α4 integrin, in adolescent patients with moderately to severely active Crohn disease (CD). Patients and Methods: In a single‐arm study, 38 adolescent patients (ages 12–17 y) with active CD (Pediatric Crohn Disease Activity Index [PCDAI] >30) received 3 intravenous infusions of natalizumab (3 mg/kg) at 0, 4 and 8 weeks. The primary analysis was safety, assessed by adverse events, laboratory results, and vital signs. Pharmacokinetic and pharmacodynamic measurements and formation of anti‐natalizumab antibodies also were analyzed. Efficacy outcomes were assessed by changes in PCDAI, quality of life (IMPACT III), and levels of C‐reactive protein and serum albumin. Results: Thirty‐one patients (82%) received 3 natalizumab infusions. The most common adverse events were headache (26%), pyrexia (21%) and CD exacerbation (24%). Clinical response (≥15‐point decrease from baseline PCDAI) and remission (PCDAI ≤10) rates were greatest at week 10 (55% and 29%, respectively). Three patients (8%) tested positive for anti‐natalizumab antibodies. The peak level (61.0 and 66.3 μg/mL) and half‐life (92.3 and 96.3 h) of natalizumab were comparable after the first and third infusions. Mean α4 integrin receptor saturation was 93% at 2 hours and