Certolizumab Pegol Injection (Cimzia®)
Pharmacology Update
Certolizumab Pegol Injection (Cimzia®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
Another monoclonal antibody to TNF-a has been approved for the treatment of Crohn's Disease. Certolizumab is a pegylated humanized Fab' fragment of an anti-TNF monoclonal antibody. It joins other anti-TNF-a drugs such as infliximab and adalimumab for this indication. Certolizumab pegol is marketed by UCB, Inc as Cimzia.
Indications
Certolizumab is indicated for the treatment of moderately-to-severely active Crohn's disease in patients who have inadequate response to conventional therapy.1
Dosage
The initial dose is 400 mg (given as 2 separate 200 mg doses) subcutaneously to separate sites on the abdomen or thigh. The dose is repeated at 2 and 4 weeks after the initial dose. The maintenance dose is 400 mg every 4 weeks. The patients should be tested for latent tuberculosis infection prior to initiating therapy.1
Certolizumab is supplied as two 200 mg vials containing powder for reconstitution, diluent, syringe and needle.
Potential Advantages
Certolizumab lacks the Fc portion of the monoclonal antibody, potentially resulting in fewer adverse events. The Fc region binds to various cell components including complement and mediates different immunologic effects such as degranulation of mast cells, apoptosis, and opsonization.
Potential Disadvantages
Certolizumab showed modest improvement in clinical response over placebo,2 however it was not statistically better than placebo in terms of remission rate at 6 and 26 weeks.
Comments
The efficacy of certolizumab in adults with moderate-to-severe Crohn's disease was shown in a 26-week, randomized, double-blind, placebo-controlled trial (PRECISE 1) (n = 660). These patients had a baseline Crohn's Diseases Activity Index (CDAI) between 220 and 450. Clinical response was defined as a decrease of CDAI of 100 or more and remission defined as a decrease of 150 or more. At 26 weeks, the response and remission rates were 37% and 29% for certolizumab and 27% and 18% for placebo respectively (p < 0.05).1,2 When both weeks 6 and 26 were considered together, certolizumab was superior to placebo in terms of clinical response (23% vs 16%, p <0.05). However, clinical remission was not statistically different (14% vs 10%). In a second study, patients with response at 6 weeks were randomized to certolizumab (400 mg every 4 weeks) or placebo through 26 weeks (PRECISE 2).3 Remission was achieved in 48% of certolizumab patients and 29% of placebo patients (p <0.05). As with other anti-TNF agents, certolizumab is less effective in TNF-alpha treatment experienced patients than treatment naïve patients. Most common adverse events are upper respiratory tract infections, urinary tract infection, and arthralgia. As with other anti-TNF drugs, there are risks for serious infections (eg, tuberculosis), malignancies (eg, lymphoma), hypersensitivity reactions, neurologic reactions (demyelinating disease), and hematologic reactions (1). Development of antibodies to certolizumab and ANA antibodies has been reported. Certolizumab costs $1316 per dose.
Clinical Implications
Anti-TNF agents are indicated for the patient with Crohn's disease who has failed conventional therapy (eg, corticosteroids, immunosuppressives). Certolizumab introduces another anti-TNF agent. Current anti-TNF therapy includes infliximab (chimeric monoclonal antibody), and adalimumab (humanized monoclonal antibody). Infliximab requires intravenous infusion while adalimumab and certolizumab are given subcutaneously. Adalimumab is self-administered and certolizumab should be injected by a healthcare provider. Chimeric monoclonal antibodies may be more immunogenic compared to humanized monoclonal antibodies. Adalimumab has been used successful in some patients who have lost responsiveness or developed intolerance to infliximab.4 There are no published comparative trials among these three agents at this time. A systematic review of pooled data in placebo-controlled studies reported that these agents showed higher clinical responses than placebo, {RR 2.19 (95% CI; 1.27-3.78)} for infliximab, {RR 2.69 (95% CI; 1.88-3.86)} for adalimumab, and {RR 1.74(95% CI; 1.41-2.13)} for certolizumab.5 For clinical remission the numbers were {RR 2.50 (95% CI; 1.64-3.80)}, {RR 2.50 (95% CI; 1.37-4.51)}, and {RR 1.68 (95% CI; 1.30-2.16)} respectively. The role of certolizumab in Crohn's disease remains to be determined.
References
1. Cimzia Product Information. UCB, Inc. April 2008.
2. Sandborn WJ, et al. N Engl J Med. 2007;357:228-238.
3. Schreiber S, et al. N Engl J Med. 2007;357:229-250.
4. Sandborn WJ, et al. Ann Intern Med. 2007;146:829-838.
5. Beh BW, Bickston SJ. Cochran Database Syst Rev 2008;Jan 23(1):CD006893.
Another monoclonal antibody to TNF-a has been approved for the treatment of Crohn's Disease.Subscribe Now for Access
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