Prescribing Reference: New Product Releases

In moderately to severely active Crohn's disease: to reduce signs and symptoms and to maintain clinical response in adult patients with inadequate response to conventional therapy.

Pharmacology:

Elevated levels of TNFα have been implicated in the pathology of Crohn's disease. Certolizumab pegol is a recombinant, humanized antibody Fab' fragment that has an affinity for human TNFα, a proinflammatory cytokine that plays a key role in the inflammatory process. TNFα stimulates the production of interleukin-1, prostaglandins, platelet activating factor, and nitric oxide. After treatment with certolizumab pegol, patients with Crohn's disease had a decrease in C-reactive protein.

Clinical trials:

Two placebo-controlled trials were conducted in patients with moderately to severely active Crohn's disease. In the first study, 662 patients were given either certolizumab pegol 400mg or placebo at weeks 0, 2, 4, and then every 4 weeks to week 24. At week 6, the proportion of clinical responders in patients on the study drug was 35%, compared to 27% for placebo; clinical remission was noted in 22% of patients given the study drug versus 17% for those given placebo. The difference in the proportion of patients who were in clinical response at weeks 6 and 26 was also significant (23% vs. 16%), indicating a maintenance of clinical response.

The second trial was a treatment-withdrawal study. All patients were dosed initially with the study drug at weeks 0, 2, and 4, and then assessed for clinical response at week 6. At week 6, a group of 428 responders was randomized to receive either certolizumab pegol 400mg or placebo every 4 weeks from week 8–24. At week 26, a statistically significantly greater proportion of week 6 responders were in clinical response and in remission (63% and 48%) compared to the placebo-treated group (36% and 29%).

The baseline use of immunosuppressants or corticosteroids had no impact on the clinical response to the study drug.

Adults:

Give by SC inj in abdomen or thigh. 400mg (two 200mg inj) on day 1, then at weeks 2 and 4; maintenance 400mg every 4 weeks.

Children:

Not recommended.

Precautions:

Active infections: not recommended. Chronic or history of recurring infections. Conditions that predispose to infection. Test for tuberculosis, treat TB first. Monitor closely for new infections, discontinue if serious infection develops. History of TB or histoplasmosis exposure. Immunosuppressed. Hepatitis B infection; discontinue if reactivation occurs. Malignancies. CNS demyelinating disorders. Hematological abnormalities. CHF. Discontinue if lupus-like syndrome or serious hypersensitivity reaction occurs. Pregnancy (Cat.B). Nursing mothers: not recommended.

Interactions:

Concurrent anakinra, live vaccines or other TNF blockers: not recommended. Immunosuppressants increase risk of infection. May interfere with coagulation tests (eg, aPPT).

Adverse reactions:

Upper respiratory infections, UTI, arthralgia, other infections; rare: TB, HBV reactivation, hypersensitivity reactions, malignancies, antibody formation.

How supplied:

Kit—1 (2 single-dose vials w. syringes, needles, supplies)

Last Updated:

6/6/08