DESCRIPTION

CIMZIA is a medicine called a Tumor Necrosis Factor (TNF) blocker. CIMZIA is used to reduce the signs and symptoms of moderately to severely active Crohn's disease in adult patients who have not been helped enough by usual treatments.

General information about CIMZIA

Medicines are sometimes prescribed for purposes that are not mentioned in Medication Guides. Do not use CIMZIA for a condition for which it was not prescribed. Do not give CIMZIA to other people, even if they have the same condition. It may harm them.

This Medication Guide summarizes the most important information about CIMZIA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about CIMZIA that is written for health professionals.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The active ingredient is certolizumab pegol.

The inactive ingredients in CIMZIA include: sucrose, lactic acid, polysorbate. No preservatives are present.

CLINICAL RESULTS

FDA Approval

FDA approval of Cimzia was based on the results of two clinical trials.

Study CD1

This randomized placebo-controlled study enrolled 662 subjects with active Crohn�s disease. The subjects received Cimzia (400 mg subcutaneously) or placebo administered at Weeks 0, 2, and 4 and then every four weeks to Week 24. Assessments were done at Weeks 6 and 26. Clinical response was defined as at least a 100-point reduction in CDAI score compared to baseline, and clinical remission was defined as an absolute CDAI score of 150 points or lower. At Week 6 the proportion of clinical responders was 35% in the Cimzia group compared to 27% in the placebo group (p-value < 0.05). Clinical remission was seen in 22% of the Cimzia group and 17% of the placebo group; this did not reach statistical significance. At Week 26 the proportion of clinical responders was 37% in the Cimzia arm and 27% in the placebo arm and clinical remission was seen in 29% of the Cimzia arm and 18% of the placebo arm (p-value < 0.05 for both endpoints).

Study CD2

All the subjects who entered this randomized treatment-withdrawal study were initially treated with Cimzia 400 mg at Weeks 0, 2, and 4. They were subsequently assessed for clinical response at Week 6 (as defined by at least a 100-point reduction in CDAI score). At Week 6, a group of 428 clinical responders were randomized to receive either Cimzia 400 mg or placebo, every four weeks starting at Week 8, as maintenance therapy through Week 24. Non-responders were withdrawn from the study. Final evaluation was based on the CDAI score at Week 26. At Week 26 the proportion of clinical responders in the Cimzia 400 mg x3 + Placebo group was 36% compared to 63% in the Cimzia 400 mg arm (p < 0.05). Clinical remission was seen in 29% of the Cimzia/placebo arm and 48% in the Cimzia arm (p < 0.05).

Ongoing Study Commitments

• UCB Pharma has agreed to conduct a study in pediatric patients, "A Phase II Open-Label Multi-Center Study to Assess the Safety and Effcacy ofCertolizumab pegol in Children and Adolescents with Active Crohn's Disease" (Study CDP870-035). This study is proposed to evaluate the pharmacokinetics, safety and clinical response of pediatric patients, ages 6-17, with moderately to severely active Crohn's disease to treatment with Cimzia.
  Protocol Submission: September 2008
  Study Start Date: June 2009
  Final Report Submission: October 2013
  
  
• UCB Pharma has agreed to a long-term observational study in the U.S. that wil include approximately 2000 Cimzia-treated Crohn's disease patients and 2000 matched controls receiving other treatments for Crohn's disease. Patients wil be monitored for ten years.
  Protocol Submission: September 2008
  Study Start Date: February 2009
  Final Report Submission: March 2020
  
  
• UCB has agreed to CDP870-033, an ongoing open-label trial to assess the long-term safety of Cimzia in patients with Crohn's disease who have previously completed trials CDP870-031 or CDP870-032. The objectives of this trial include measurement of pharmacokinetics and antibody response in Cimzia-treated patients. Patient follow-up wil be extended to seven years from the start of treatment.
  Protocol Amendment Submission: October 2008
  Trial Start Date: Ongoing
  Final Report Submission: May 2013
  
  
• UCB Pharma has agreed to CDP870-034, an ongoing open-label trial to assess the long-term safety of re-exposure to Cimzia after a variable interval in patients with Crohn's disease who were previously withdrawn from completed trials CDP870-031 or CDP870-032 due to an exacerbation of Crohn's disease. The objectives of this trial include measurement of pharmacokinetics and antibody response in Cimzia-treated patients. Patient follow-up wil be extended to seven years from the start of treatment.
  Protocol Amendment Submission: October 2008
  Trial Start Date: Ongoing
  Final Report Submission: May 2013
  
  
• UCB Pharma has agreed to CDP870-088, an open-label trial to assess the long-term safety of Cimzia in patients with Crohn's disease who have either completed trial CDP870-085 or were withdrawn from CDP870-085 due to an exacerbation of Crohn's disease. The objectives of this trial include measurement of pharmacokinetics and antibody response in Cimzia-treated patients. Patient follow-up wil be extended to five years from the start of treatment.
  Protocol Amendment Submission: October 2008
  Trial Start Date: May 2008
  Final Report Submission: May 2015
  
  
• UCB Pharma has agreed to a placebo-controlled trial designed to assess the effects of Cimzia treatment on antibody responses to a B cell-mediated immunization, using pneumococcal vaccine immunization, and to a T cell-mediated immunization, using influenza vaccine, in patients with active rheumatoid arthritis. The study wil measure both antibody titers and rates of clinical response in approximately 100 placebo- and 100 Cimzia-treated patients who wil be given polyvalent pneumococcal polysaccharide vaccine and influenza vaccine.
  Protocol Submission: October 2008
  Trial Start Date: October 2009
  Final Report Submission: March 2011

SIDE EFFECTS

Adverse events associated with the use of Cimzia may include, but are not limited to, the following:

• upper respiratory infection
• urinary tract infection
• arthralgia
• abdominal pain
• diarrhea
• intestinal obstruction

MECHANISM OF ACTION

Certolizumab pegol is a humanized, pegylated tumor necrosis factor alpha (TNF-a) inhibitor. TNFa is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFa (IC90 of 4 ng/mL for inhibition of human TNFa in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralize lymphotoxin a (TNF-beta). Certolizumab pegol was shown to neutralize membrane-associated and soluble human TNFa in a dose-dependent manner.

LITERATURE REFERENCES

Rutgeerts P, Schreiber S, Feagan B, Keininger DL, O'Neil L, Fedorak RN; CDP870 Crohn's Disease Study Group Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn's disease. International Journal of Colorectal Disease 2008 Mar;23(3):289-96

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, Bloomfield R, Schreiber S; PRECISE 1 Study Investigators Certolizumab pegol for the treatment of Crohn's disease. The New England Journal of Medicine 2007 Jul 19;357(3):228-38

Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, Bernstein CN, Staun M, Thomsen OO, Innes A; CDP870 Crohn's Disease Study Group A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005 Sep;129(3):807-18

Winter TA, Wright J, Ghosh S, Jahnsen J, Innes A, Round P Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study. Alimentary Pharmacology & Therapeutics 2004 Dec;20(11-12):1337-46

INFORMATION FOR PATIENTS

CIMZIA is a medicine called a Tumor Necrosis Factor (TNF) blocker. CIMZIA is used to reduce the signs and symptoms of moderately to severely active Crohn's disease in adult patients who have not been helped enough by usual treatments.

What is the most important information I should know about CIMZIA?

CIMZIA is a medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections, including tuberculosis (TB), have happened in patients taking CIMZIA. Some patients have died from these infections.

• Your doctor should test you for TB before starting CIMZIA
  
  
• Your doctor should monitor you closely for signs and symptoms of TB during treatment with CIMZIA

PRECAUTIONS

You should not receive CIMZIA if you have had an allergic reaction to CIMZIA, or any of the ingredients in CIMZIA. See the end of the Medication Guide for a complete list of ingredients in CIMZIA.

• think you have an infection (see "What is the most important information I should know about CIMZIA?")
• are being treated for an infection
• have signs of an infection, such as a fever, cough, flu-like symptoms
• have any open cuts or sores on your body
• get a lot of infections or have infections that keep coming back
• have diabetes
• have HIV
• have tuberculosis (TB), or have been in close contact with someone with TB
• have or have had hepatitis B
• have or have had any type of cancer
• have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis
• have heart failure
• are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA
• are pregnant, planning to become pregnant, or breastfeeding. CIMZIA has not been studied in pregnant or nursing women
• are taking any medicines, including prescription and nonprescription medicines, vitamins and herbal supplements. Your doctor will tell you if it is okay to take your other medicines while taking CIMZIA. Especially tell your doctor if you take Kineret� (anakinra). You have a higher chance for serious infections when taking CIMZIA with Kineret�

• CIMZIA should be injected by a healthcare provider. Each dose of CIMZIA will be given as two separate injections under the skin in your stomach area (abdomen) or upper leg (thigh)
• Make sure to keep all of your injection and follow-up appointments with your doctor

ADVERSE REACTIONS

What are the possible side effects of CIMZIA?
Serious side effects have happened in patients taking CIMZIA including:

• Serious infections including tuberculosis (TB). See "What is the most important information I should know about CIMZIA?"
• Cancer including lymphoma
• Nervous System Problems such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes. Symptoms include dizziness, numbness or tingling, problems with your vision, and weakness in your arms or legs
• Allergic Reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing
• Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include a fever that doesn't go away, bruising or bleeding very easily, or looking very pale
• Heart Failure including new heart failure or worsening of heart failure you already have. Symptoms include shortness of breath, or swelling of your ankles or feet
• Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure

• Upper respiratory infections (flu, cold)
• Urinary tract infections (bladder infections)
• Joint pain

• Serious infections including tuberculosis (TB). See �What is the most important information I should know about CIMZIA?�
• Cancer including lymphoma.
• Nervous System Problems such as Multiple Sclerosis, seizures, or inflammation of the nerves of the eyes. Symptoms include dizziness, numbness or tingling, problems with your vision, and weakness in your arms or legs.
• Allergic Reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing.
• Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include a fever that doesn't go away, bruising or bleeding very easily, or looking very pale.
• Heart Failure including new heart failure or worsening of heart failure you already have. Symptoms include shortness of breath, or swelling of your ankles or feet.
• Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.

Cimzia is a registered trademark of UCB.

©2008, UCB, All rights reserved.