Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(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.
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PMID:Certolizumab pegol: new drug. As a last resort in Crohn's disease: continue to use other TNF alpha inhibitors. 1963 18

Biologic therapies have revolutionized the treatment of Crohn's disease (CD). Targeting TNF-alpha with monoclonal antibodies has changed the therapeutic landscape for tackling refractory and complicated CD. Intravenous use of infliximab, a chimeric monoclonal antibody to TNF-alpha is, however, limited by the occurrence of adverse events, infusion reactions, infectious complications, aggravation of heart failure, the occurrence of neurological demyelinating conditions and induction of rare malignancies. The incremental development of next-generation TNF-alpha antibodies and binding proteins through antibody-engineering techniques has followed, with the aim of producing efficacious drugs that are less expensive to produce, have a convenient route of administration and have fewer side effects. Certolizumab pegol (CDP870, Cimzia) is an engineered humanized anti-TNF-alpha antibody Fab fragment that minimizes the protein component and is conjugated to polyethylene glycol. Clinical studies have demonstrated efficacy in the treatment of moderate-to-severe active CD. Reported adverse events in the clinical trial program have been largely of mild-to-moderate severity, and occurred at similar frequencies in the active-treatment and placebo groups. Certolizumab pegol will be a useful addition to the armamentarium of biologic agents that can be used for the long-term treatment of CD.
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PMID:Treatment of Crohn's disease with certolizumab pegol. 2047 19