Cimzia is a humanized, pegylated tumor necrosis factor alpha (TNF-a) inhibitor. TNFa is a key pro-inflammatory cytokine with a central role in inflammatory processes.
Cimzia is specifically indicated for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
Cimzia is supplied as a powder for reconstitution into a liquid formulation designed for subcutaneous administration. The recommended initial dose of the drug is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at Weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.
FDA approval of Cimzia was based on the results of two clinical trials.
This randomized placebo-controlled study enrolled 662 subjects with active Crohn’s disease. The subjects received Cimzia (400 mg subcutaneously) or placebo administered at Weeks 0, 2, and 4 and then every four weeks to Week 24. Assessments were done at Weeks 6 and 26. Clinical response was defined as at least a 100-point reduction in CDAI score compared to baseline, and clinical remission was defined as an absolute CDAI score of 150 points or lower. At Week 6 the proportion of clinical responders was 35% in the Cimzia group compared to 27% in the placebo group (p-value < 0.05). Clinical remission was seen in 22% of the Cimzia group and 17% of the placebo group; this did not reach statistical significance. At Week 26 the proportion of clinical responders was 37% in the Cimzia arm and 27% in the placebo arm and clinical remission was seen in 29% of the Cimzia arm and 18% of the placebo arm (p-value < 0.05 for both endpoints).
All the subjects who entered this randomized treatment-withdrawal study were initially treated with Cimzia 400 mg at Weeks 0, 2, and 4. They were subsequently assessed for clinical response at Week 6 (as defined by at least a 100-point reduction in CDAI score). At Week 6, a group of 428 clinical responders were randomized to receive either Cimzia 400 mg or placebo, every four weeks starting at Week 8, as maintenance therapy through Week 24. Non-responders were withdrawn from the study. Final evaluation was based on the CDAI score at Week 26. At Week 26 the proportion of clinical responders in the Cimzia 400 mg x3 + Placebo group was 36% compared to 63% in the Cimzia 400 mg arm (p < 0.05). Clinical remission was seen in 29% of the Cimzia/placebo arm and 48% in the Cimzia arm (p < 0.05).
Ongoing Study Commitments
Adverse events associated with the use of Cimzia may include, but are not limited to, the following:
Certolizumab pegol is a humanized, pegylated tumor necrosis factor alpha (TNF-a) inhibitor. TNFa is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFa (IC90 of 4 ng/mL for inhibition of human TNFa in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralize lymphotoxin a (TNFß). Certolizumab pegol was shown to neutralize membrane-associated and soluble human TNFa in a dose-dependent manner.
Rutgeerts P, Schreiber S, Feagan B, Keininger DL, O'Neil L, Fedorak RN; CDP870 Crohn's Disease Study Group Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn's disease. International Journal of Colorectal Disease 2008 Mar;23(3):289-96
Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, Bloomfield R, Schreiber S; PRECISE 1 Study Investigators Certolizumab pegol for the treatment of Crohn's disease. The New England Journal of Medicine 2007 Jul 19;357(3):228-38
Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, Bernstein CN, Staun M, Thomsen OØ, Innes A; CDP870 Crohn's Disease Study Group A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005 Sep;129(3):807-18
Winter TA, Wright J, Ghosh S, Jahnsen J, Innes A, Round P Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study. Alimentary Pharmacology & Therapeutics 2004 Dec;20(11-12):1337-46
For additional information regarding Cimzia or Crohn's disease, please visit the Cimzia web page.