The use of adalimumab in the management of refractory Crohn's disease.
BACKGROUND
Adalimumab is a humanized monoclonal antibody targeting tumour necrosis factor-alpha. Recent clinical trials have demonstrated its efficacy in Crohn's disease; however, experience in clinical practice remains limited.


OBJECTIVE
To investigate the efficacy and safety of adalimumab in the clinical setting.


METHODS
The clinical outcomes of patients with medically refractory Crohn's disease treated with adalimumab in the Western General Hospital Edinburgh, over a 3-year period (2003-2006), were studied.


RESULTS
Twenty-two (14 females; age at therapy: 32.6 years) patients were treated using an 80/40 mg induction regimen followed by fortnightly 40 mg treatment. All had proven refractory/intolerant to corticosteroids and immunosuppression. Twenty patients had had previous infliximab infusions - of these eight (36%), six (27%), three (14%) had previous infusion reactions, no response and lost response to infliximab, respectively. Over a period of 1.0 years (IQR: 0.62-2.5), Kaplan-Meier analyses showed that 68% (seven nonresponders) were in clinical remission and 67% (five surgery - discounting oral CD) avoided further surgery for active disease. 59% required dose escalation to 40 mg weekly (0.55 years; IQR: 0.22-1.4). Three (50%) primary nonresponders to infliximab achieved remission. Two patients developed serious infective complications and one patient developed lung cancer.


CONCLUSIONS
Adalimumab is efficacious in refractory Crohn's disease, with benefit observed in infliximab primary nonresponders. However, many patients require escalation of dosing regimen.
Ho
G-T
GT
Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. gwotzerho@aol.com
Smith
L
L
Aitken
S
S
Lee
H M
HM
Ting
T
T
Fennell
J
J
Lees
C W
CW
Palmer
K R
KR
Penman
I D
ID
Shand
A G
AG
Arnott
I D
ID
Satsangi
J
J
D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015331:Cohort Studies; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab