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.