Certolizumab pegol for the treatment of Crohn's disease.
BACKGROUND
Certolizumab pegol is a pegylated humanized Fab' fragment that binds tumor necrosis factor alpha.


METHODS
In a randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol in 662 adults with moderate-to-severe Crohn's disease. Patients were stratified according to baseline levels of C-reactive protein (CRP) and were randomly assigned to receive either 400 mg of certolizumab pegol or placebo subcutaneously at weeks 0, 2, and 4 and then every 4 weeks. Primary end points were the induction of a response at week 6 and a response at both weeks 6 and 26.


RESULTS
Among patients with a baseline CRP level of at least 10 mg per liter, 37% of patients in the certolizumab group had a response at week 6, as compared with 26% in the placebo group (P=0.04). At both weeks 6 and 26, the corresponding values were 22% and 12%, respectively (P=0.05). In the overall population, response rates at week 6 were 35% in the certolizumab group and 27% in the placebo group (P=0.02); at both weeks 6 and 26, the response rates were 23% and 16%, respectively (P=0.02). At weeks 6 and 26, the rates of remission in the two groups did not differ significantly (P=0.17). Serious adverse events were reported in 10% of patients in the certolizumab group and 7% of those in the placebo group; serious infections were reported in 2% and less than 1%, respectively. In the certolizumab group, antibodies to the drug developed in 8% of patients, and antinuclear antibodies developed in 2%.


CONCLUSIONS
In patients with moderate-to-severe Crohn's disease, induction and maintenance therapy with certolizumab pegol was associated with a modest improvement in response rates, as compared with placebo, but with no significant improvement in remission rates. (ClinicalTrials.gov number, NCT00152490 [ClinicalTrials.gov].).
Sandborn
William J
WJ
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. sandborn.william@mayo.edu
Feagan
Brian G
BG
Stoinov
Simeon
S
Honiball
Pieter J
PJ
Rutgeerts
Paul
P
Mason
David
D
Bloomfield
Ralph
R
Schreiber
Stefan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000906:Antibodies; D000974:Antibodies, Antinuclear; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein / Q000032:analysis; D000068582:Certolizumab Pegol; D003424:Crohn Disease / Q000145:classification / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000974:Antibodies, Antinuclear; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D002097:C-Reactive Protein; D000068582:Certolizumab Pegol