Certolizumab pegol: new drug. As a last resort in Crohn's disease: continue to use other TNF alpha inhibitors.
(1) Infliximab and adalimumab, two TNF alpha-inhibitor immunosuppressants, are both available for use as a last resort in Crohn's disease. They are effective in about one in two patients but they carry a risk of serious infections, lymphoma and aggravation of heart failure; (2) Certolizumab is a new TNF alpha-inhibitor monoclonal antibody. It is pegylated to prolong its action, hence the name certolizumab pegol; (3) Certolizumab is sold in the United States for the treatment of Crohn's disease, after failure of conventional treatments. However, the European authorities issued a negative opinion on this drug, and the European Commission refused to grant marketing authorization on 21 May 2008. It is nonetheless available for named-patient compassionate use in France; (4) Certolizumab pegol has not been compared directly with infliximab or adalimumab; (5) In a double-blind placebo-controlled trial including 662 adults with an exacerbation of Crohn's disease, a 6-month course of certolizumab pegol reduced symptom intensity in slightly more patients than placebo (23% versus 16%). However, the rate of clinical remissions was similar (about 12% of patients overall); (6) In a placebo-controlled trial in 428 patients with an initial critical response to certolizumab pegol, maintaining this treatment for 6 months was more effective than switching to placebo. Clinical remissions were obtained at the end of treatment in respectively 48% and 29% of patients; (7) These short-term trials showed a higher frequency of infections with certolizumab pegol than with placebo; these infections ranged from mild respiratory tract infections to fatal tuberculosis. Some patients also developed autoantibodies and anti-certolizumab pegol antibodies, but the clinical implications are unclear. There is also evidence of an excess risk of haemorrhage. The risk of long-term adverse effects remains to be determined; (8) Certolizumab pegol is injected subcutaneously, once a month, on an outpatient basis, while adalimumab is injected twice a month; (9) In practice, as with other TNF alpha inhibitors used in Crohn's disease, certolizumab pegol is only modestly effective and carries a disturbing risk of adverse effects. In the absence of a better alternative, patients with Crohn's disease who might benefit from TNF alpha inhibitor therapy should continue to receive either infliximab or adalimumab, two drugs with which we have more experience.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D003362:Cost-Benefit Analysis; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D017277:Drug Approval; D005060:Europe; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol