Certolizumab pegol (Cimzia): Tumor necrosis factor blocker approved for the treatment of moderate-to-severe Crohn's disease

New biologic: Certolizumab pegol (Cimzia), a tumor necrosis factor blocker, was approved on April 22, 2008, for the reduction of the signs and symptoms of Crohn's disease and the maintenance of clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

This recombinant, humanized antibody Fab' fragment selectively neutralizes tumor necrosis factor (TNF)-alpha; elevated levels of TNF-alpha have been linked to Crohn's disease. Certolizumab pegol was approved on April 22, 2008, for the reduction of the signs and symptoms of Crohn's disease and the maintenance of clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

Efficacy. The efficacy of certolizumab pegol was evaluated in 2 double-blind, randomized, placebo-controlled studies. The studies enrolled patients aged ≥18 years with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI], 220–450 points). In Study CD1, patients were randomized to treatment with subcutaneous (SC) certolizumab pegol 400 mg or placebo at Weeks 0, 2, and 4, and then every 4 weeks thereafter through Week 24. Response to therapy was assessed at Weeks 6 and 26. Clinical response was defined as a ≥100-point reduction in CDAI score from baseline; clinical remission was defined as an absolute CDAI score of ≤150 points. At Week 6, 35% of certolizumab pegol-treated patients demonstrated a clinical response versus 27% of placebo-treated patients (P<.05), and 22% of certolizumab pegol-treated patients demonstrated clinical remission versus 17% of placebo-treated patients. At Week 26, 37% of certolizumab pegol-treated patients demonstrated a clinical response versus 27% of placebo-treated patients (P<.05), and 29% of certolizumab pegol-treated patients demonstrated clinical remission versus 18% of placebo-treated patients (P<.05). At both Weeks 6 and 26, 23% of certolizumab pegol-treated patients demonstrated a clinical response versus 16% of placebo-treated patients (P<.05). In Study CD2, all patients were initially treated with certolizumab pegol 400 mg at Weeks 0, 2, and 4 and were evaluated for clinical response at Week 6. All patients who demonstrated a clinical response were then randomized to treatment with either certolizumab pegol 400 mg or placebo every 4 weeks from Week 8 through Week 24. Clinical response and remission rates were assessed at Week 26. At this time point, 63% of certolizumab pegol-treated patients demonstrated a clinical response versus 36% of placebo-treated patients (P<.05), and 48% of certolizumab pegol-treated patients demonstrated clinical remission versus 29% of placebo-treated patients (P<.05).

Safety. Treatment with TNF blockers has been associated with serious infections, sepsis, and cases of opportunistic infections, including fatalities. Treatment with certolizumab pegol has been associated with tuberculosis, including some fatal cases. The use of TNF blockers may increase the risk of hepatitis B virus (HBV) reactivation. In clinical studies, more cases of malignancies have been reported in patients treated with TNF blockers versus those treated with control medication. TNF blockers have been associated with rare cases of new-onset or exacerbation of existing demyelinating disease. TNF blockers have also been associated with rare cases of pancytopenia. Treatment with certolizumab pegol may result in the formation of autoantibodies. The most common adverse events associated with certolizumab pegol treatment include upper respiratory tract infection, urinary tract infection, and arthralgia.