Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease.
BACKGROUND
Crohn's disease may be refractory to conventional treatments including corticosteroids and immunosuppressives. Recent studies suggest TNF-alpha blocking agents may be effective in maintaining remission in Crohn's disease.


OBJECTIVE
To conduct a systematic review of the evidence for the effectiveness of TNF-alpha blocking agents in the maintenance of remission in patients with Crohn's disease.


METHODS
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the IBD/FBD Review Group Specialized Trials Register were searched for relevant studies published between 1966-2007. Manual searches of references from potentially relevant papers were performed to identify additional studies. Experts in the field and study authors were contacted to identify unpublished data.


METHODS
Randomized controlled trials involving patients > 18 years with Crohn's disease who had a clinical response or clinical remission with a TNF-alpha blocking agent, or patients with Crohn's disease in remission but unable to wean corticosteroids, who were then randomized to maintenance of remission with a TNF-alpha blocking agent or placebo


METHODS
Two independent authors performed data extraction and assessment of the methodological quality of each trial. Outcome measures reported in the primary studies included clinical remission, clinical response, and steroid-sparing effects.


RESULTS
Nine studies met all inclusion criteria. Four different anti-TNF-alpha agents were evaluated (infliximab in 3 studies, CDP571 in 3 studies, adalimumab in 2 studies, and certolizumab in 1 study). There is evidence from three randomized controlled trials that infliximab maintains clinical remission (RR 2.50; 95% CI 1.64 to 3.80), maintains clinical response (RR 1.66; 95% CI 1.00 to 2.76), has corticosteroid-sparing effects (RR 3.13; 95% CI 1.25 to 7.81), and maintains fistula healing (RR 1.87; 95% CI 1.15 to 3.04) in patients with Crohn's disease with a response to infliximab induction therapy. There were no significant differences in remission rates between infliximab doses of 5 mg/kg or 10 mg/kg. There is evidence from two randomized controlled trials that adalimumab maintains clinical remission (RR 2.86; 95% CI 2.01 to 4.02), maintains clinical response (RR 2.69; 95% CI 1.88 to 3.86), and has corticosteroid-sparing effects (RR 2.81, 95% CI 1.46 to 5.43) in patients with Crohn's disease who have responded or entered remission with adalimumab induction therapy. There were no significant differences in remission rates between adalimumab 40 mg weekly or every other week. There is evidence from one randomized controlled trial that certolizumab pegol maintains clinical remission (RR 1.68; 95% CI 1.30 to 2.16) and maintains clinical response (RR 1.74; 95% CI 1.41 to 2.13) in patients who have responded to certolizumab induction therapy. There is no evidence to support the use of CDP571 for the maintenance of remission in Crohn's disease.


CONCLUSIONS
Infliximab 5 mg/kg or 10 mg/kg, given every 8 weeks, is effective for the maintenance of remission and maintenance of fistula healing in patients who have responded to infliximab induction therapy. Adalimumab 40 mg weekly or every other week is effective for the maintenance of remission in patients who have responded to adalimumab induction therapy. Certolizumab pegol 400 mg every 4 weeks is effective for the maintenance of remission in patients who have responded to certolizumab induction therapy. No comparative trials have evaluated the relative efficacy of these agents. Adverse events are similar in the infliximab, adalimumab, and certolizumab groups compared with placebo, but study size and duration generally are insufficient to allow an adequate assessment of serious adverse events associated with long-term use.
Behm
B W
BW
Bickston
S J
SJ
D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D000069285:Infliximab; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol