Retrospective Evaluation of the Safety and Effect of Adalimumab Therapy (RESEAT) in pediatric Crohn's disease.
OBJECTIVE
Adalimumab, an anti-tumor necrosis factor immunoglobulin-1 antibody, is increasingly being reported as a potential treatment option for children with moderate-to-severe Crohn's disease (CD). The aim of this study was to characterize common indications, safety, tolerability, and clinical response to adalimumab in pediatric CD in a large, multicenter, patient cohort.


METHODS
Data were obtained using a retrospective, uncontrolled chart review at 12 sites of the Pediatric Inflammatory Bowel Disease Collaborative Research Group. Clinical, laboratory, and demographic data were obtained for CD patients who received at least one dose of adalimumab. Indication for adalimumab, concomitant medications, and clinical outcome at 3, 6, and 12 months for each patient were recorded using physician global assessment (PGA) and Pediatric CD Activity Index scores. Serious adverse events were identified.


RESULTS
A total of 115 patients (54% female) received at least one dose of adalimumab. The mean age at the diagnosis of CD was 11.1+/-3.1 years, with the first adalimumab dose administered at 4.7+/-2.8 years after diagnosis. The most common dosing frequency was every other week with induction doses of 160/80 mg in 19%, 80/40 mg in 44%, and 40/40 mg in 15% of patients. Maintenance dosing was 40 mg every other week in 88% of patients. Mean follow-up after initial adalimumab dose was 10+/-8.6 months. Infliximab treatment preceded adalimumab in 95% of patients, with a mean of 12 infliximab infusions (range: 1-44). Infliximab discontinuation was due to loss of response (47%), infusion reaction or infliximab intolerance (45%), or preference for a subcutaneous medication (9%). Concomitant medications at the commencement of adalimumab were corticosteroids (38%), azathioprine/6-mercaptopurine (41%), and methotrexate (23%). Clinical response measured by PGA at 3, 6, and 12 months was 65, 71, and 70%, respectively, with steroid-free remission at 3, 6, and 12 months of 22, 33, and 42%, respectively. There were no malignancies, serious infections, or deaths in the study subjects.


CONCLUSIONS
Adalimumab was a well-tolerated and effective rescue therapy for moderate-to-severe pediatric CD patients previously treated with infliximab. Adalimumab demonstrated a steroid-sparing effect, and >70% of patients achieved rapid response that was sustained through 12 months.
Rosh
Joel R
JR
Division of Pediatric Gastroenterology, Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey 07962 , USA. joel.rosh@atlantichealth.org
Lerer
Trudy
T
Markowitz
James
J
Goli
Sri R
SR
Mamula
Petar
P
Noe
Joshua D
JD
Pfefferkorn
Marian D
MD
Kelleher
Kathleen T
KT
Griffiths
Anne M
AM
Kugathasan
Subra
S
Keljo
David
D
Oliva-Hemker
Maria
M
Crandall
Wallace
W
Carvalho
Ryan S
RS
Mack
David R
DR
Hyams
Jeffrey S
JS
D000068879:Adalimumab; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016009:Chi-Square Distribution; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab