Natalizumab therapy for moderate to severe Crohn disease in adolescents.
OBJECTIVE
This study evaluated the safety, tolerability, and efficacy of natalizumab, a humanized monoclonal immunoglobulin-G4 antibody to [alpha]4 integrin, in adolescent patients with moderately to severely active Crohn disease (CD).


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 (> or =15-point decrease from baseline PCDAI) and remission (PCDAI < or =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 microg/mL) and half-life (92.3 and 96.3 h) of natalizumab were comparable after the first and third infusions. Mean [alpha]4 integrin receptor saturation was 93% at 2 hours and <40% at 4 weeks after the first and third infusions. Increase from baseline in circulating lymphocytes ranged from 106% to 122% at 2 weeks and 45% to 65% at 4 weeks after each infusion.


CONCLUSIONS
Natalizumab (3 mg/kg) was well tolerated in these adolescent patients with active CD, with a safety and efficacy profile similar to that of adult natalizumab-treated CD patients. Future studies should evaluate long-term safety and efficacy.
Hyams
Jeffrey S
JS
Division of Digestive Diseases and Nutrition, Connecticut Children's Medical Center, Hartford, CT 06106, USA. jhyams@ccmckids.org
Wilson
David C
DC
Thomas
Adrian
A
Heuschkel
Robert
R
Mitton
Sally
S
Mitchell
Brent
B
Daniels
Regina
R
Libonati
Michele A
MA
Zanker
Susan
S
Kugathasan
Subra
S
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D039441:Integrin alpha4 / Q000276:immunology; D008297:Male; D000069442:Natalizumab; D011788:Quality of Life; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D039441:Integrin alpha4