Indication: CIMZIA is approved for the treatment of adults with moderate to severe rheumatoid arthritis (RA).
Important Safety Information: Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.
Please see additional Important Safety Information inside this brochure and accompanying full Prescribing Information.
You can find the RA treatment support you want.
You don’t have to do this alone.
F o r a d u lt s w i t h m o d e r at e t o s e v e r e
r h e u m at o i d a r t h r i t i s ( r a )
There is a way forward.
When you’re seeking relief from moderate to severe rheumatoid arthritis symptoms, you don’t have to do this alone. Together with your doctor, we are here to provide education and treatment support. You can count on us throughout your journey.
What is rheumatoid arthritis?
Rheumatoid arthritis (RA) is a chronic inflammatory disorder. When your RA is active, inflammation is occurring. Inflammation causes joint pain and stiffness, and over time this inflammation can also cause damage to your joints.
What is CIMZIA
®(certolizumab pegol)
?
CIMZIA is a prescription injectable medication approved for the treatment of adults with moderate to severe rheumatoid arthritis. CIMZIA can be taken alone or with methotrexate (MTX).
CIMZIA is a PEGylated TNF blocker
CIMZIA is the first and only PEGylated biologic treatment for rheumatoid arthritis. The PEGylation process has been shown to help the medicine stay in the body. For dosing information, see page 4 of this brochure.
Important Safety Information: There have been cases of unusual cancers in children and teenage patients using TNF blockers. For people taking TNF blockers, including CIMZIA, the chances of getting lymphoma may increase. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma. CIMZIA is not approved for use in pediatric patients.
Use of TNF blockers, including CIMZIA, may increase the risk of hepatitis B virus reactivation in patients who carry the virus in their blood. In some cases, patients have died as a result of hepatitis B virus being reactivated. Symptoms include feeling unwell, skin or eyes looking yellow, tiredness (fatigue), poor appetite or vomiting, and pain on the right side of your stomach (abdomen).
Indication: CIMZIA is approved for the treatment of adults with
moderate to severe rheumatoid arthritis (RA).
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
How does CIMZIA
®work?
When your RA is active, inflammation is occurring, leading to joint pain and stiffness. And ongoing inflammation can also cause damage to your joints. CIMZIA works by blocking the action of TNF, a protein produced by the immune system that causes inflammation.
3 3
Indication: CIMZIA is approved for the treatment of adults with moderate to severe rheumatoid
arthritis (RA).
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
CIMZIA
®delivered noticeable, proven
relief for adults with moderate to
severe RA.
CIMZIA (certolizumab pegol) clinical study results:
(your results may vary)
Noticeable RA relief:
In clinical trials, CIMZIA was proven versus placebo to provide noticeable RA symptom relief including improvement in pain, swelling, and tenderness for the majority of patients within 24 weeksand for some as quickly as 1–2 weeks.
CIMZIA stopped further joint damage
for most patients as shownby their X-rays at both 6 months and one year in a clinical trial versus patients in a control group.
Improvement in common everyday activities:
In a clinical trial,patients on CIMZIA for 6 months reported improvement in everyday activities like showering, getting dressed, doing chores, walking short
distances, and running simple errands.
The clinical study results above were based on patients receiving the recommended initial loading and maintenance dosing.
Talk to your doctor to see if CIMZIA is right for you.
Important Safety Information: Patients 65 years of age or older, patients with other long-term medical conditions, or patients taking certain other drugs that affect the immune system, such as corticosteroids or methotrexate, may be at a greater risk of infection.
Immune reactions including a lupus-like syndrome have happened in people taking CIMZIA. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.
Indication: CIMZIA is approved for the treatment of adults with
moderate to severe rheumatoid arthritis (RA).
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
Get started with CIMZIA
®(certolizumab pegol)
There are two dosing phases that patients may follow on CIMZIA —initial dosing and maintenance dosing.
Ask your doctor about the CIMZIA initial “Loading Doses.”
Initial Dosing:
Initial dosing covers your first month of injections which are provided at the start of therapy at Week 0, Week 2, and Week 4. Each of these doses is 400 mg, given as two separate injections under the skin of 200 mg each. After you complete your initial dosing, your doctor will tell you which maintenance dose you should take.
Maintenance Dosing:
After you complete your initial dosing phase, there are two flexible maintenance dosing options available to you:
•
one 200 mg injection taken every 2 weeks or•
two 200 mg injections taken every 4 weeks.Important Safety Information: Allergic reactions may occur. Signs of an allergic reaction include a skin rash, swelling or itching of the face, tongue, lips or throat, or trouble breathing.
CIMZIA is available in two formulations:
•
A prefilled syringe you can use at home.If your doctor decides home self-injections are appropriate, you can use the prefilled syringe. You should receive injection training from your doctor or we can send a nurse to your home for a training session, free of charge. Alternatively, a friend or loved one can be trained how to assist you.
•
A powder that is mixed, prepared and injected by a healthcare professional at your doctor’s office.LOADING DOSE* MAINTENANCE DOSE*
2 INJECTIONS WEEK 0 2 INJECTIONS WEEK 2 2 INJECTIONS WEEK 4 400 mg 2 x 200 mg/mL 400 mg 2 x 200 mg/mL 2 x 200 mg/mL400 mg EVERY 2 WEEKS 200 mg/mL 1 INJECTION EVERY 4 WEEKS 2 X 200 mg/mL 2 INJECTIONS OR
*For subcutaneous administration. Please see section 2 of full Prescribing Information for additional dosing and administration information.
You and your doctor should decide which maintenance dosing is best for you. You will receive complete dosing instructions from your doctor.
Reminder: Be sure to inject both syringes, one right after another. Remember to talk to your doctor about dosing instructions.
Important Safety Information you should know about CIMZIA® (certolizumab pegol)
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 have happened in patients taking CIMZIA, including
tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.
• Your healthcare provider should test you for TB before starting CIMZIA.
• Your healthcare provider should monitor you closely for signs and symptoms of TB during treatment with CIMZIA.
You should not start receiving CIMZIA if you have any kind of infection unless your healthcare provider says it is okay.
Before you receive CIMZIA, tell your healthcare provider if you:
• think you have an infection, flu-like symptoms, or have any other symptoms of an infection such as: • fever, sweat, or chills • weight loss
• muscle aches • warm, red, or painful skin or sores on your body • cough • diarrhea or stomach pain
• shortness of breath • burning when you urinate or urinate more often than normal • blood in phlegm • feeling very tired
• are being treated for an infection, or get a lot of infections or have infections that keep coming back • have diabetes, HIV, or a weak immune system. People with these conditions have a higher chance
for infections.
• have tuberculosis (TB), or have been in close contact with someone with TB
• were born in, lived in, or traveled to countries where there is more risk of getting TB. Ask your healthcare provider if you are not sure.
• live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis). These infections may develop or become more severe if you take CIMZIA. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your healthcare provider.
• have or have had hepatitis B
• use the medicine Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab), or Tysabri®
(natalizumab)
After starting CIMZIA, if you get an infection, any sign of an infection including a fever, cough,
flu-like symptoms, or have open cuts or sores on your body, call your healthcare provider right away. CIMZIA can make you more likely to get infections or make any infection that you may have worse.
Certain Types of Cancer
There have been cases of unusual cancers in children and teenage patients using TNF-blocking agents. CIMZIA is not approved for use in pediatric patients. For people taking TNF-blocker medicines, including CIMZIA, the chances for getting lymphoma or other cancers may increase. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma.
What is CIMZIA?
CIMZIA is a prescription medicine called a Tumor Necrosis Factor (TNF) blocker. CIMZIA is used in adult patients to:
• Lessen the signs and symptoms of moderately to severely active Crohn’s disease (CD) in patients who have not been helped enough by usual treatments.
• Treat moderately to severely active rheumatoid arthritis (RA). • Treat active psoriatic arthritis (PsA).
• Treat active ankylosing spondylitis (AS).
What should I tell my healthcare provider before starting treatment with CIMZIA?
CIMZIA may not be right for you. Before starting CIMZIA, tell your healthcare provider about all of your medical conditions, including if you:
• have an infection
• have or have had any type of cancer • have congestive heart failure
• have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis
• are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA. • are allergic to any of the ingredients in CIMZIA
• are pregnant or planning to become pregnant. It is not known if CIMZIA will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while receiving CIMZIA.
Pregnancy Registry: If you become pregnant while taking CIMZIA, talk to your healthcare provider about registering in the pregnancy exposure registry for CIMZIA. You can enroll in this registry by calling 1-877-311-8972. The purpose of this registry is to collect information about the safety of CIMZIA during pregnancy.
• are breastfeeding or plan to breastfeed. It is not known if CIMZIA passes into your breast milk. You and your healthcare provider should decide if you will receive CIMZIA or breastfeed.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take the following medicines due to a higher chance for serious infections:
• Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab), or Tysabri® (natalizumab)
• medicines called Tumor Necrosis Factor (TNF) blockers, such as Remicade® (infliximab), Humira®
(adalimumab), Enbrel® (etanercept), or Simponi® (golimumab)
Ask your healthcare provider if you are not sure. You should not take CIMZIA while you take any of these medicines.
How should I receive CIMZIA?
CIMZIA comes as a lyophilized powder or a solution in a prefilled syringe for injection. If your healthcare provider prescribes the CIMZIA powder, CIMZIA should be injected by a healthcare provider. If your healthcare provider prescribes the prefilled syringe, you will be trained on how to inject CIMZIA. See the booklet called “Instructions for Use” packaged in your CIMZIA prefilled syringe kit for complete instructions for use. Do not give yourself an injection of CIMZIA unless you have been shown by your healthcare provider, or they can train someone you know to help you with your injection. CIMZIA is given by an injection under the skin. Your healthcare provider will tell you how much and how often to inject CIMZIA. Do not use more CIMZIA or inject more often than prescribed.
What are the possible side effects of CIMZIA? CIMZIA can cause serious side effects including:
• Heart Failure including new heart failure or worsening of heart failure you already have. Symptoms
include shortness of breath, swelling of your ankles or feet, or sudden weight gain.
• Allergic Reactions. Signs of an allergic reaction include a skin rash, swelling or itching of the face,
tongue, lips, or throat, or trouble breathing.
• Hepatitis B virus reactivation in patients who carry the virus in their blood. In some cases,
patients have died as a result of hepatitis B virus being reactivated. Your healthcare provider should monitor you carefully before and during treatment with CIMZIA to see if you carry the hepatitis B virus in your blood. Tell your healthcare provider if you have any of the following symptoms:
• feel unwell • poor appetite or vomiting
• skin or eyes look yellow • pain on the right side of your stomach (abdomen) • tiredness (fatigue)
• New or worsening nervous system problems, such as multiple sclerosis (MS), Guillain-Barre
syndrome, seizures, or inflammation of the nerves of the eyes. Symptoms may include: • dizziness
• numbness or tingling • problems with your vision • weakness in your arms or legs
• 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.
• 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.
Call your healthcare provider right away if you have any side effects listed above. The most common side effects of CIMZIA include: upper respiratory infections (flu, cold), rash, and urinary tract infections (bladder infections).
Tell your healthcare provider about any side effect that bothers you or does not go away. These are not all of the possible side effects of CIMZIA. For more information, ask your healthcare provider or pharmacist.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please see the Medication Guide for CIMZIA and discuss it with your healthcare provider. All other medications are registered trademarks of their respective owners.
Important Safety Information: Heart failure, including new heart failure or worsening of heart failure, has been reported in people taking CIMZIA. Symptoms include shortness of breath, swelling of your ankles or feet, or sudden weight gain.
Indication: CIMZIA is approved for the treatment of adults with
moderate to severe rheumatoid arthritis (RA).
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
Treatment support you can depend on.
When it comes to your treatment, you can count on us for the tools and support you need to help you start and stay on your treatment with CIMZIA®
(certolizumab pegol) through our program called CIMplicity®.Making treatment
support easy for patients is our mission.
Our CIMplicity program will provide financial assistance and ongoing education. If your doctor decides home self-injections are right for you, we can send a nurse to your home to teach you how.
Call CIMplicity at 1-866-4-CIMZIA (1-866-424-6942). Select option 2.
Monday–Friday 8:00 a.m. –8:00 p.m. E.S.T.
CIMplicity
—
Simplifying treatment support:
Insurance coordination
: Help coordinating insurance verification foryour CIMZIA coverage which may be covered under your prescription plan or your medical insurance.
Nurse support:
Call a nurse to ask questions. You can even arrange to have a nurse come to your home to give free injection training to you.Ongoing education and other tools:
Sign up online at www.CIMZIA.comto receive helpful RA education, medication reminders, tools, and the latest information about CIMZIA. You can request a free sharps syringe disposal kit too.
Financial help:
Financial assistance for both uninsured and insured patients.*Eligibility: Not valid for prescriptions that are reimbursed, in whole or in part, under Medicare (including Medicare Part D), Medicaid, similar federal or state funded programs (including any state prescription drug assistance programs and the Government Health Insurance Plan available in Puerto Rico) or where otherwise prohibited by law. Product dispensed pursuant to program rules and federal and state laws. Claims should not be submitted to any public payor (i.e., Medicare, Medicaid, Medigap, Tricare, VA, and DoD) for reimbursement. Patients and pharmacists are responsible for notifying insurance carriers or any other third party who pays for or reimburses any part of the prescription filled using this card as may be required by the insurance carrier’s terms and conditions and applicable law. The maximum annual benefit amount is $11,000 per calendar year. The parties reserve the right to amend or end this program at any time without notice.
†The 2013 program included a tiered benefit design; the July 2014 program eliminated these tiers.
$0 Co-Pay
Because cost shouldn’t get in the way
of your treatment.
(Eligibility restrictions and maximum limits apply)*
• No income requirements
• No dollar limit per use
• Available for either drug co-pays or
annual deductible
• In 2013, over 97% of CIMZIA Co-Pay Savings
Card claims resulted in no out-of-pocket costs
for those program participants.
†There are three easy ways to obtain a $0 Co-Pay Savings Card:
•
At your doctor’s office: Ask your healthcare professional for a card.•
Telephone: By calling 1-866-4-CIMZIA(866-424-6942), option 1
•
Online: By visiting www.CIMZIA.com/signupFor the uninsured, we have a patient assistance program (PAP). Call 1-866-395-8366, option 4
More Resources
www.CIMZIA.com is a go-to source for information about CIMZIA®, a treatment
for adults with moderate to severe active rheumatoid arthritis (RA). You may also find these resources helpful for learning about and managing your RA:
American College of Rheumatology
This organization works to advance rheumatology treatment through programs to improve care for people with rheumatic and musculoskeletal diseases and arthritis. www.rheumatology.org
Arthritis Foundation
The Foundation works to advance the treatment of more than 100 types of arthritis and related conditions. www.arthritis.org, 1-800-283-7800 Arthritis Today Magazine
Arthritis Today is the consumer health magazine published by the Arthritis
Foundation. www.arthritis.org/resources/arthritis-today-magazine
National Data Bank for Rheumatic Diseases
The National Data Bank (NDB) is the largest patient-reported research data bank for rheumatic disorders in the United States. The NDB works to improve treatment outcomes for people with rheumatic disorders.
www.arthritis-research.org
National Institute of Arthritis and Musculoskeletal and Skin Diseases
The Institute supports research into the causes, treatment, and prevention of arthritis and of musculoskeletal and skin diseases. www.niams.nih.gov
UCBCaresTM
1-844-599-CARE (2273), or email [email protected]
For a UCBCares associate, press option 3. For adverse events, press option 1. Monday–Friday 8:00 a.m. –5:00 p.m. E.S.T.
Indication: CIMZIA is approved for the treatment of adults with
moderate to severe rheumatoid arthritis (RA).
Important Safety Information: There have been rare reports of blood problems with CIMZIA use. 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.
You should not take CIMZIA with Kineret® (anakinra), Orencia®
(abatacept), Rituxan® (rituximab), Tysabri® (natalizumab), Remicade®
(infliximab), Humira® (adalimumab), Enbrel® (etanercept), or Simponi®
(golimumab) due to an increased risk of serious infections.
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
Important Safety Information: New or worsening of nervous system problems may occur, such as multiple sclerosis, Guillain-Barre syndrome, 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.
Glossary of Terms
These are some terms you may hear. Please talk to your doctor if you need more explanation. Anemia: Abnormally low levels of healthy red blood cells or of hemoglobin (the part of
the blood that carries oxygen).
Antibody: A protein that is part of the body’s natural immune defense system and that
helps identify and neutralize foreign substances in the body.
Anti-cyclic citrullinated peptide (anti-CCP) antibodies: A biomarker used to diagnose
rheumatoid arthritis and to help predict the course of the disease; the presence of anti-CCP antibodies is measured using a blood test and is positive in many RA patients.
Antinuclear antibodies (ANAs): A group of antibodies that may be present in people
who have an immune disease. ANAs may also be present in people who do not have an immune disease.
Anti-TNF therapy: A medicine that works by blocking a protein called tumor necrosis
factor (TNF)- alpha in the body.
Autoimmune disorder/disease: A condition that occurs when the immune system
attacks and/or damages healthy body tissue by mistake. There are more than 80 types of autoimmune disorders, including rheumatoid arthritis.
Biologic: A substance originating from a living source that is used to treat disease. Biologic response modifiers: These drugs are derived from living sources and target
and block proteins in the immune system that play a role in triggering inflammation.
Bone: A single unit of the skeleton. Bones provide shape and support, store minerals,
and serve as a place where blood cells are made. Bones surround and protect organs, and give points of attachment for the muscles, which allows the body to move.
Cartilage: A tough but flexible connective tissue that covers the ends of bones at a
joint and is also found in other parts of the body, such as the ears and air passages. Healthy cartilage allows bones to glide over each other, and prevents them from rubbing against each other.
Clinical Disease Activity Index (CDAI): A measure of RA disease activity and severity
based on the number of specific tender and swollen joints and both the patient’s and physician’s overall assessment of health. Higher scores indicate more severe disease. (See also Simplified Disease Activity Index.)
Corticosteroids*: Drugs used to slow down the immune system and help reduce
inflammation. Corticosteroids are sometimes used in the treatment of inflammatory diseases, such as rheumatoid arthritis.
C-reactive protein (CRP): A protein made by the liver. High CRP levels in the blood are
a sign of inflammation.
Disease Activity Score (DAS): A measure of disease activity in rheumatoid arthritis.
To determine a person’s DAS, a healthcare provider will examine the joints for swelling and tenderness, review results of blood tests, and talk to the patient about his or her symptoms. (See also Clinical Disease Activity Index; Disease Activity Score including 28 joints; Simplified Disease Activity Index.)
Disease Activity Score including 28 joints (DAS28): A measure of disease activity in
rheumatoid arthritis. A DAS28 is calculated using the number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate, and a patient’s assessment of his or her overall health. A DAS28 greater than 5.1 is the definition of active disease.
A DAS28 less than 3.2 means that the disease is well controlled. A DAS28 less than 2.6 is associated with remission.
Disease-modifying antirheumatic drugs (DMARDs): Treatments that slow down the
way that rheumatoid arthritis progresses.
Erosion: The wearing away or destruction of the surface of a tissue, material, or
structure.
Flare, flare-up: An increase in the severity of a person’s clinical disease symptoms. Health Assessment Questionnaire (HAQ): A set of questions that assesses physical
function by asking patients about their ability to do everyday activities.
Immune system: The system of the body that involves the cells and biochemical
processes responsible for defending against foreign substances, such as infections.
Immunomodulators, immunosuppressants: Treatments used for many clinical
conditions, including rheumatoid arthritis; immunomodulators for rheumatoid arthritis work by reducing the immune system response.
Inflammation: A series of reactions that normally activate cells and molecules of the
immune system to prevent infection or repair tissue damage.
Intravenous (IV): A way of putting medication directly into the vein, usually through a
needle or tube, to allow direct access to the blood. In rheumatoid arthritis, IV injection of medication may be done at an infusion center.
Joint: The point where 2 bones meet. A freely movable joint is one in which the bone
ends are covered with a thin sheet of cartilage and joined by ligament lined by a synovial membrane. (See also Synovial membrane.)
Remission: A period of time when signs or symptoms of a disease are minimal or absent.
Rheumatoid arthritis (RA): An autoimmune disease that causes pain, swelling, stiffness, and loss of function in the joints. Rheumatoid arthritis can affect many joints, but is common in the wrists and fingers.
Rheumatoid factor (RF): An antibody present in the serum (fluid portion of the blood) of 50% to 95% of adults with rheumatoid arthritis. RF is helpful in diagnosing and investigating the disease.
Rheumatoid nodule: Lump of tissue that forms under the skin, occurring most commonly over bony areas, in some patients with rheumatoid arthritis.
Rheumatologist: A doctor who is qualified by additional training and experience in the diagnosis and treatment of arthritis and other diseases of the joints, muscles, and bones.
Rheumatology: A specialty of internal medicine dedicated to the diagnosis and management of disorders affecting the connective tissue and related structures of the body.
Simplified Disease Activity Index (SDAI): A measure of the severity of rheumatoid arthritis that is made up of the sum of the following: tender and swollen joint counts (28 joints), patient and physician assessments of disease activity, and level of C-reactive protein. Higher scores indicate greater disease activity.
Steroids*: A class of drugs that reduce inflammation and slow down the body’s immune system response and that are often used to treat chronic inflammatory conditions, including Crohn’s disease and rheumatoid arthritis.
Subcutaneous injection: A way of administering medication under the skin, as opposed to injection into a muscle (intramuscular) or directly into a vein (intravenous).
Synovial membrane: The connective tissue membrane that lines the cavity (hollow space) of a joint.
Synovitis: Inflammation of a synovial membrane. Synovitis can be used as another term for arthritis.
Trigger: Something that either sets off a disease in a person who is genetically inclined to develop the disease, or that causes a certain symptom to occur in a person who has a disease.
Tumor necrosis factor-alpha (TNF-alpha; TNF-α): A protein (known as a cytokine)
produced by the immune system that is involved in the process of inflammation. Too much TNF-α can contribute to the symptoms of rheumatoid arthritis. Joint space narrowing: Thinning space between joints; by measuring the width of joint
space, a healthcare provider can monitor the progression of disease.
Lyophilized: Freeze-dried. When CIMZIA is given by a doctor or nurse it is in the form of
a lyophilized powder before it is mixed with sterile water and injected.
Magnetic resonance imaging (MRI): A technique that uses electromagnetic energy to
produce images of the soft tissues in the central nervous and musculoskeletal systems.
Maintenance therapy: A therapy given to improve/maintain current health status to try
to prevent a relapse of disease.
Methotrexate: A nonbiologic DMARD (disease-modifying antirheumatic drug) that may
be prescribed alone, in combination with other DMARDs, or in combination with a biologic.
Morning stiffness: Joint and muscle stiffness that is present on awakening and is
associated with various types of inflammatory arthritis. The stiffness tends to decrease as activity is increased during the day.
Nonsteroidal anti-inflammatory drugs (NSAIDs): A class of drugs that reduces pain,
inflammation, and fever. There is no evidence that NSAIDs change the progression of a disease such as rheumatoid arthritis.
Occupational therapy: A form of treatment that involves changing a person’s
environment or the way that he or she completes daily tasks to increase his or her ability to function independently and to prevent further disability.
Pathology: The study of disease; also, the causes, development, and processes of
a disease.
PEGylation: A chemical process of changing a molecule by the addition of polyethylene
glycol (PEG) to help extend its ability to work in the body.
Physical therapy: A form of treatment that uses exercise, massage, assistive devices,
and patient education and training to preserve, improve, or bring back movement and physical function.
Polyethylene glycol (PEG): A chemical used to change a protein or drug so that its
removal by the body is delayed or stopped, thereby extending its ability to work in the body.
Radiographic progression: The extent to which a person with rheumatoid arthritis
has sustained permanent damage to the joints. X-ray images are used to measure the degree of change between 2 time points.
Radiography: The examination of any part of the body by means of X-ray images.
Thank you.
We understand that each person’s journey with RA is unique and often times may not be easy. We are inspired by you and how you are taking action to take care of yourself or a loved one. We are focused on supporting and helping you.
CIMZIA® is made by UCB, a global biopharmaceutical company.
UCB is passionate about helping patients and their families with chronic severe diseases, such as rheumatoid arthritis.
Please see pages 6–7 for additional Important Safety Information and accompanying full Prescribing Information.
Get the facts about CIMZIA
®(certolizumab pegol):
Then ask your doctor today if CIMZIA is right for you to treat your active moderate to severe RA symptoms.
If you’re still not noticing the symptom relief you want, it may be time to talk to your doctor.
Ask your doctor:
• What can I expect from treating my moderate to severe RA with CIMZIA? • How quickly could I expect symptom relief with CIMZIA?
• How is CIMZIA administered and how often do I take it?
• What are the possible safety concerns and side effects of CIMZIA?
Sign up online for more information:
www.CIMZIA.com/signup
Indication: CIMZIA is approved for the treatment of adults with moderate to severe rheumatoid
arthritis (RA).
Important Safety Information: Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.
Please see additional Important Safety Information inside this brochure and accompanying full Prescribing Information.
OXO, Good Grips, and the associated logos are registered trademarks of Helen of Troy Limited and are used under license. CIMZIA®, CIMplicity®, and cimplicity® are registered trademarks, and the UCBCaresTM logo is a trademark, of the UCB Group of Companies. © 2014 UCB, Inc. All rights reserved. CZP-PRM-031171-0914A
F o r a d u lt s w i t h m o d e r at e t o s e v e r e
r h e u m at o i d a r t h r i t i s ( r a )
FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: SERIOUS INFECTIONS AND MALIGNANCY
1 INDICATIONS AND USAGE
1.1 Crohn’s Disease 1.2 Rheumatoid Arthritis 1.3 Psoriatic Arthritis 1.4 Ankylosing Spondylitis
2 DOSAGE AND ADMINISTRATION
2.1 Crohn’s Disease 2.2 Rheumatoid Arthritis 2.3 Psoriatic Arthritis 2.4 Ankylosing Spondylitis
2.5 Preparation and Administration of CIMZIA Using the Lyophilized Powder for Injection 2.6 Preparation and Administration of CIMZIA Using the Prefilled Syringe
2.7 Monitoring to Assess Safety 2.8 Concomitant Medications
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Risk of Serious Infections 5.2 Malignancies 5.3 Heart Failure 5.4 Hypersensitivity Reactions 5.5 Hepatitis B Virus Reactivation 5.6 Neurologic Reactions 5.7 Hematological Reactions
5.8 Use with Biological Disease-Modifying Antirheumatic Drugs (Biological DMARDs) 5.9 Autoimmunity
5.10 Immunizations 5.11 Immunosuppression
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Use with Anakinra, Abatacept, Rituximab and Natalizumab 7.2 Live Vaccines
7.3 Laboratory Tests
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility
14 CLINICAL STUDIES 14.1 Crohn’s Disease 14.2 Rheumatoid Arthritis 14.3 Psoriatic Arthritis 14.4 Ankylosing Spondylitis 15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION
17.1 Patient Counseling
17.2 Instruction on Prefilled Syringe Self-Injection Technique *Sections or subsections omitted from the full prescribing information are not listed.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use CIMZIA®safely and
effectively. See full prescribing information for CIMZIA.
CIMZIA (certolizumab pegol) for injection, for subcutaneous use CIMZIA (certolizumab pegol) injection, for subcutaneous use Initial U.S. Approval: 2008
———————————-———- INDICATIONS AND USAGE
————————————-——-CIMZIA is a tumor necrosis factor (TNF) blocker indicated for:
• Reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy (1.1)
• Treatment of adults with moderately to severely active rheumatoid arthritis (1.2) • Treatment of adult patients with active psoriatic arthritis. (1.3)
• Treatment of adults with active ankylosing spondylitis (1.4)
—————————————— DOSAGE AND ADMINISTRATION ————————-————
CIMZIA is administered by subcutaneous injection. The initial dose of CIMZIA is 400 mg (given as two subcutaneous injections of 200 mg) (2).
Crohn’s Disease (2.1)
• 400 mg initially and at Weeks 2 and 4. If response occurs, follow with 400 mg every four weeks
Rheumatoid Arthritis (2.2)
• 400 mg initially and at Weeks 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered.
Psoriatic Arthritis (2.3)
• 400 mg initially and at week 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered
Ankylosing Spondylitis (2.4)
• 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks.
————————————— DOSAGE FORMS AND STRENGTHS —————————————
• For injection: 200 mg lyophilized powder for reconstitution in a single-use vial, with 1 mL of sterile Water for Injection (3)
• Injection: 200 mg/mL solution in a single-use prefilled syringe (3)
——————————————— CONTRAINDICATIONS
———————————————-• None (4)
————————————— WARNINGS AND PRECAUTIONS ——————————————
• Serious infections – do not start CIMZIA during an active infection. If an infection develops, monitor carefully, and stop CIMZIA if infection becomes serious (5.1)
• Invasive fungal infections – for patients who develop a systemic illness on CIMZIA, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic (5.1) • Cases of lymphoma and other malignancies have been observed among patients receiving TNF
blockers (5.2)
• Heart failure, worsening or new onset may occur (5.3) • Anaphylaxis or serious allergic reactions may occur (5.4)
• Hepatitis B virus reactivation – test for HBV infection before starting CIMZIA. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop CIMZIA and begin anti-viral therapy (5.5)
• Demyelinating disease, exacerbation or new onset, may occur (5.6)
• Cytopenias, pancytopenia – advise patients to seek immediate medical attention if symptoms develop, and consider stopping CIMZIA (5.7)
• Lupus-like syndrome – stop CIMZIA if syndrome develops (5.9)
————————————-——- ADVERSE REACTIONS
————————-———————-The most common adverse reactions (incidence ≥7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-866-822-0068 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
—————————————-—- DRUG INTERACTIONS
———————————-————-• Use with Biological DMARDs – increased risk of serious infections (5.8, 7.1) • Live vaccines – avoid use with CIMZIA (5.10, 7.2)
• Laboratory tests – may interfere with aPTT tests (7.3)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 10/2015
WARNING: SERIOUS INFECTIONS AND MALIGNANCY
See full prescribing information for complete boxed warning.• Increased risk of serious infections leading to hospitalization or death including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens (5.1). • CIMZIA should be discontinued if a patient develops a serious infection or
sepsis (5.1).
• Perform test for latent TB; if positive, start treatment for TB prior to starting CIMZIA (5.1).
• Monitor all patients for active TB during treatment, even if initial latent TB test is negative (5.1).
• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member (5.2). CIMZIA is not indicated for use in pediatric patients (8.4).
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Crohn’s Disease
CIMZIA is indicated for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
1.2 Rheumatoid Arthritis
CIMZIA is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA).
1.3 Psoriatic Arthritis
CIMZIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).
1.4 Ankylosing Spondylitis
CIMZIA is indicated for the treatment of adults with active ankylosing spondylitis (AS). [see
Clinical Studies (14.4)]
2 DOSAGE AND ADMINISTRATION
CIMZIA is administered by subcutaneous injection. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard. When a 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen.
The solution should be carefully inspected visually for particulate matter and discoloration prior to administration. The solution should be a clear colorless to yellow liquid, essentially free from particulates and should not be used if cloudy or if foreign particulate matter is present. CIMZIA does not contain preservatives; therefore, unused portions of drug remaining in the syringe or vial should be discarded.
2.1 Crohn’s Disease
The recommended initial adult dose of CIMZIA is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at Weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.
2.2 Rheumatoid Arthritis
The recommended dose of CIMZIA for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at Weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, CIMZIA 400 mg every 4 weeks can be considered [see Clinical Studies (14.2)].
2.3 Psoriatic Arthritis
The recommended dose of CIMZIA for adult patients with psoriatic arthritis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at week 2 and 4, followed by 200 mg every other week. For maintenance dosing, CIMZIA 400 mg every 4 weeks can be considered [see Clinical Studies
(14.3)].
2.4 Ankylosing Spondylitis
The recommended dose of CIMZIA for adult patients with ankylosing spondylitis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.
2.5 Preparation and Administration of CIMZIA Using the Lyophilized Powder for Injection
CIMZIA Lyophilized powder should be prepared and administered by a health care professional. CIMZIA is provided in a package that contains everything required to reconstitute and inject the drug
are provided below. Preparation and Storage
a. CIMZIA should be brought to room temperature before reconstituting. b. Use appropriate aseptic technique when preparing and administering CIMZIA.
c. Reconstitute the vial(s) of CIMZIA with 1 mL of Sterile Water for Injection, USP using the 20-gauge needle provided.
d. Gently swirl each vial of CIMZIA without shaking, assuring that all of the powder comes in contact with the Sterile Water for Injection.
e. Leave the vial(s) undisturbed to fully reconstitute, which may take approximately 30 minutes. f. The final reconstituted solution contains 200 mg/mL and should be clear to opalescent,
colorless to pale yellow liquid essentially free from particulates.
g. Once reconstituted, CIMZIA can be stored in the vials for up to 24 hours between 2° to 8° C (36° to 46° F) prior to injection. Do not freeze.
Administration
a. Prior to injecting, reconstituted CIMZIA should be at room temperature but do not leave reconstituted CIMZIA at room temperature for more than two hours prior to administration. b. Withdraw the reconstituted solution into a separate syringe for each vial using a new
20-gauge needle for each vial so that each syringe contains 1 mL of CIMZIA (200 mg of certolizumab pegol).
c. Replace the 20-gauge needle(s) on the syringes with a 23-gauge(s) for administration. d. Inject the full contents of the syringe(s) subcutaneously into thigh or abdomen. Where a 400 mg
dose is required, two injections are required, therefore, separate sites should be used for each 200 mg injection.
2.6 Preparation and Administration of CIMZIA Using the Prefilled Syringe
After proper training in subcutaneous injection technique, a patient may self-inject with the CIMZIA Prefilled Syringe if a physician determines that it is appropriate.
Patients using the CIMZIA Prefilled Syringe should be instructed to inject the full amount in the syringe (1 mL), according to the directions provided in the Instructions for Use booklet.
2.7 Monitoring to Assess Safety
Before initiation of therapy with CIMZIA, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. The possibility of undetected latent tuberculosis should be considered in patients who have immigrated from or traveled to countries with a high prevalence of tuberculosis or had close contact with a person with active tuberculosis. Appropriate screening tests (e.g. tuberculin skin test and chest x-ray) should be performed in all patients.
2.8 Concomitant Medications
CIMZIA may be used as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs).
The use of CIMZIA in combination with biological DMARDs or other tumor necrosis factor (TNF) blocker therapy is not recommended.
3 DOSAGE FORMS AND STRENGTHS
• For Injection: Lyophilized Powder for Reconstitution
Sterile, white, lyophilized powder for reconstitution and then subcutaneous administration. Each single-use vial provides approximately 200 mg of CIMZIA.
• Injection: Prefilled Syringe
A single-use, 1 mL prefilled glass syringe with a fixed 25 gauge ½ inch thin wall needle, providing 200 mg per 1 mL of CIMZIA.
4 CONTRAINDICATIONS None.
5 WARNINGS AND PRECAUTIONS
5.1 Risk of Serious Infections
[see Boxed Warning]
Patients treated with CIMZIA are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.
Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.
Treatment with CIMZIA should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g. corticosteroids or methotrexate) may be at a greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients:
• with chronic or recurrent infection • who have been exposed to tuberculosis • with a history of an opportunistic infection
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis
• with underlying conditions that may predispose them to infection
Tuberculosis
Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving CIMZIA, including patients who have previously received treatment for latent or active tuberculosis. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating CIMZIA and periodically during therapy.
WARNING: SERIOUS INFECTIONS AND MALIGNANCY SERIOUS INFECTIONS
Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1) and Adverse
Reactions (6.1)]. Most patients who developed these infections were taking concomitant
immunosuppressants such as methotrexate or corticosteroids.
CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:
• Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before CIMZIA use and during therapy. Treatment for latent infection should be initiated prior to CIMZIA use.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness. • Bacterial, viral and other infections due to opportunistic pathogens, including
Legionella and Listeria.
The risks and benefits of treatment with CIMZIA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)]. MALIGNANCY
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member [see Warnings
Calmette-Guerin (BCG).
Anti-tuberculosis therapy should also be considered prior to initiation of CIMZIA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision of whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Tuberculosis should be strongly considered in patients who develop a new infection during CIMZIA treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.
Monitoring
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with CIMZIA.
CIMZIA should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with CIMZIA should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated.
Invasive Fungal Infections
For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and risks of antifungal therapy.
5.2 Malignancies
In the controlled portions of clinical studies of some TNF blockers, more cases of malignancies have been observed among patients receiving TNF blockers compared to control patients. During controlled and open-labeled portions of CIMZIA studies of Crohn’s disease and other diseases, malignancies (excluding non-melanoma skin cancer) were observed at a rate (95% confidence interval) of 0.5 (0.4, 0.7) per 100 patient-years among 4,650 CIMZIA-treated patients versus a rate of 0.6 (0.1, 1.7) per 100 patient-years among 1,319 placebo-treated patients. The size of the control group and limited duration of the controlled portions of the studies precludes the ability to draw firm conclusions.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which CIMZIA is a member. Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous post-marketing reports. CIMZIA is not indicated for use in pediatric patients.
In the controlled portions of clinical trials of all the TNF blockers, more cases of lymphoma have been observed among patients receiving TNF blockers compared to control patients. In controlled studies of CIMZIA for Crohn’s disease and other investigational uses, there was one case of lymphoma among 2,657 Cimzia-treated patients and one case of Hodgkin’s lymphoma among 1,319 placebo-treated patients.
In the CIMZIA RA clinical trials (placebo-controlled and open label) a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma.
Rates in clinical studies for CIMZIA cannot be compared to the rates of clinical trials of other TNF blockers and may not predict the rates observed when CIMZIA is used in a broader patient population. Patients with Crohn’s disease that require chronic exposure to immunosuppressant therapies may be at higher risk than the general population for the development of lymphoma, even in the absence of TNF blocker therapy [see Adverse Reactions (6.1)]. The potential role of TNF blocker therapy in the development of malignancies in adults is not known.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported in patients treated with TNF blockers, including CIMZIA. The majority of reported TNF blocker cases occurred in adolescent and young adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine (6-MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk of using a TNF blocker in combination with azathioprine or 6-MP should be carefully considered.
Cases of acute and chronic leukemia have been reported in association with post-marketing TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer.
5.3 Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including CIMZIA. CIMZIA has not been formally studied in patients with CHF; however, in clinical studies in patients with CHF with another TNF blocker, worsening congestive heart failure (CHF) and increased mortality due to CHF were observed. Exercise caution in patients with heart failure and monitor them carefully [see Adverse Reactions (6.1)].
5.4 Hypersensitivity Reactions
The following symptoms that could be compatible with hypersensitivity reactions have been reported rarely following CIMZIA administration to patients: angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria. Some of these reactions occurred after the first administration of CIMZIA. If such reactions occur,
Use of TNF blockers, including CIMZIA, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation.
Test patients for HBV infection before initiating treatment with CIMZIA. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with CIMZIA should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.
In patients who develop HBV reactivation, discontinue CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of CIMZIA therapy in this situation and monitor patients closely.
5.6 Neurologic Reactions
Use of TNF blockers, of which CIMZIA is a member, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of CIMZIA in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with CIMZIA [see
Adverse Reactions (6.1)].
5.7 Hematological Reactions
Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) have been infrequently reported with CIMZIA [see Adverse Reactions (6.1)]. The causal relationship of these events to CIMZIA remains unclear.
Although no high risk group has been identified, exercise caution in patients being treated with CIMZIA who have ongoing, or a history of, significant hematologic abnormalities. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA. Consider discontinuation of CIMZIA therapy in patients with confirmed significant hematologic abnormalities.
5.8 Use with Biological Disease-Modifying Antirheumatic Drugs (Biological DMARDs)
Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF blocker, etanercept, with no added benefit compared to entanercept alone. A higher risk of serious infections was also observed in combination use of TNF blockers with abatacept and rituximab. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the use of CIMZIA in this combination. Therefore, the use of CIMZIA in combination with other biological DMARDs is not recommended [see Drug Interactions (7.1)].
5.9 Autoimmunity
Treatment with CIMZIA may result in the formation of autoantibodies and rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with CIMZIA, discontinue treatment [see Adverse Reactions (6.1)].
5.10 Immunizations
Patients treated with CIMZIA may receive vaccinations, except for live or live attenuated vaccines. No data are available on the response to live vaccinations or the secondary transmission of infection by live vaccines in patients receiving CIMZIA.
In a placebo-controlled clinical trial of patients with rheumatoid arthritis, no difference was detected in antibody response to vaccine between CIMZIA and placebo treatment groups when the pneumococcal polysaccharide vaccine and influenza vaccine were administered concurrently with CIMZIA. Similar proportions of patients developed protective levels of anti-vaccine antibodies between CIMZIA and placebo treatment groups; however patients receiving CIMZIA and concomitant methotrexate had a lower humoral response compared with patients receiving CIMZIA alone. The clinical significance of this is unknown.
5.11 Immunosuppression
Since TNF mediates inflammation and modulates cellular immune responses, the possibility exists for TNF blockers, including CIMZIA, to affect host defenses against infections and malignancies. The impact of treatment with CIMZIA on the development and course of malignancies, as well as active and/or chronic infections, is not fully understood [see Warnings and Precautions (5.1, 5.2, 5.5) and Adverse Reactions (6.1)]. The safety and efficacy of CIMZIA in patients with immunosuppression has not been formally evaluated. 6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
The most serious adverse reactions were:
• Serious Infections [see Warnings and Precautions (5.1)] • Malignancies [see Warnings and Precautions (5.2)] • Heart Failure [see Warnings and Precautions (5.3)]
Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice.
In premarketing controlled trials of all patient populations combined the most common adverse reactions (≥ 8%) were upper respiratory infections (18%), rash (9%) and urinary tract infections (8%).
Adverse Reactions Most Commonly Leading to Discontinuation of Treatment in Premarketing Controlled Trials
The proportion of patients with Crohn’s disease who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for CIMZIA and 7% for placebo. The most common adverse reactions leading to the discontinuation of CIMZIA (for at least 2 patients and with a higher incidence than placebo) were abdominal pain (0.4% CIMZIA, 0.2% placebo), diarrhea (0.4% CIMZIA, 0% placebo), and intestinal obstruction (0.4% CIMZIA, 0% placebo).
The proportion of patients with rheumatoid arthritis who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for CIMZIA and 2.5% for placebo. The most common adverse reactions leading to discontinuation of CIMZIA were tuberculosis infections (0.5%); and pyrexia, urticaria, pneumonia, and rash (0.3%).
