Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn's disease.
BACKGROUND
Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug.


OBJECTIVE
We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated.


METHODS
Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs.


METHODS
All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months.


RESULTS
After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen.


CONCLUSIONS
In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.
Borrelli
O
O
Division of Paediatric Gastroenterology, Department of Paediatrics, University of Rome La Sapienza, Viale Regina Elena, Rome 324-00161, Italy.
Bascietto
C
C
Viola
F
F
Bueno de Mesquita
M
M
Barbato
M
M
Mancini
V
V
Bosco
S
S
Cucchiara
S
S
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D001799:Blood Sedimentation; D001827:Body Height / Q000502:physiology*; D001835:Body Weight / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004334:Drug Administration Schedule; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D007262:Infusions, Intravenous; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D012709:Serum Albumin / Q000032:analysis
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D006454:Hemoglobins; D007166:Immunosuppressive Agents; D012709:Serum Albumin; D002097:C-Reactive Protein; D000069285:Infliximab; D001379:Azathioprine